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Sample records for neonatal diabetes mutations

  1. Insulin gene mutations as a cause of permanent neonatal diabetes.

    Science.gov (United States)

    Støy, Julie; Edghill, Emma L; Flanagan, Sarah E; Ye, Honggang; Paz, Veronica P; Pluzhnikov, Anna; Below, Jennifer E; Hayes, M Geoffrey; Cox, Nancy J; Lipkind, Gregory M; Lipton, Rebecca B; Greeley, Siri Atma W; Patch, Ann-Marie; Ellard, Sian; Steiner, Donald F; Hattersley, Andrew T; Philipson, Louis H; Bell, Graeme I

    2007-09-18

    We report 10 heterozygous mutations in the human insulin gene in 16 probands with neonatal diabetes. A combination of linkage and a candidate gene approach in a family with four diabetic members led to the identification of the initial INS gene mutation. The mutations are inherited in an autosomal dominant manner in this and two other small families whereas the mutations in the other 13 patients are de novo. Diabetes presented in probands at a median age of 9 weeks, usually with diabetic ketoacidosis or marked hyperglycemia, was not associated with beta cell autoantibodies, and was treated from diagnosis with insulin. The mutations are in critical regions of the preproinsulin molecule, and we predict that they prevent normal folding and progression of proinsulin in the insulin secretory pathway. The abnormally folded proinsulin molecule may induce the unfolded protein response and undergo degradation in the endoplasmic reticulum, leading to severe endoplasmic reticulum stress and potentially beta cell death by apoptosis. This process has been described in both the Akita and Munich mouse models that have dominant-acting missense mutations in the Ins2 gene, leading to loss of beta cell function and mass. One of the human mutations we report here is identical to that in the Akita mouse. The identification of insulin mutations as a cause of neonatal diabetes will facilitate the diagnosis and possibly, in time, treatment of this disorder.

  2. AB125. Neonatal diabetes mellitus due to insulin gene mutation

    Science.gov (United States)

    Can, Ngoc Thi Bich; Vu, Dung Chi; Bui, Thao Phuong; Nguyen, Khanh Ngoc; Nguyen, Dat Phu; Craig, Maria; Ellard, Sian; Nguyen, Hoan Thi

    2015-01-01

    Background and objective Insulin (INS) gene mutations that cause permanent neonatal diabetes mellitus change single protein building blocks (amino acids) in the protein sequence. These mutations are believed to disrupt the cleavage of the proinsulin chain or the binding of the A and B chains to form insulin, leading to impaired blood sugar control. At least ten mutations in the INS gene have been identified in people with permanent neonatal diabetes mellitus. To describe clinical features and laboratory manifestations of patients with INS gene mutation and to evaluate outcome of management. Methods Clinical features, biochemical finding, mutation analysis and management outcome of six cases from six unrelated families were study. All exons of INS gene were amplified from genomic DNA and directly sequenced. Results Six cases (three girls and three boys) onset at 129.2±128.8 days of age (median 101.5 days) with gestation age of 37.3±3.0 weeks, birth weight of 2,816.6±767.8 g. Five out of six patients admitted with the feature of diabetic ketoacidosis with pH of 7.04±0.22; plasma glucose levels were 34.3±12.7 mmoL/L, HbA1C of 9.75%±3.5%. Mutation analysis of the INS gene showed: heterozygous for a novel missense mutation (c.127T > A; C43S) in exon 2 in one case; heterozygous for a splicing mutation c.188-31G > A in intron 2 in two cases; heterozygous for a missense mutation c.286T > C in exon 3 in one case; heterozygous for a missense mutation c.265C > T [p.Arg89Cys (p.R89C)] in exon 3 in two cases. After 19.2±13.4 months of insulin treatment, 4/5 patients have normal development with DQ 80-100%, HbA1C of 6.85%±0.49%, quite normal blood glucose levels. The case with c.127T > A mutation treated with insulin for 14 years has physical development delay, poor blood glucose control with HbA1C of 11.4%. Conclusions It is important to perform screening gene mutation for patients with diabetes diagnosed before 6 months of age to control blood glucose and follow up the

  3. A Turkish newborn infant with cerebellar agenesis/neonatal diabetes mellitus and PTF1A mutation.

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    Tutak, E; Satar, M; Yapicioğlu, H; Altintaş, A; Narli, N; Hergüner, O; Bayram, Y

    2009-01-01

    Classical neonatal diabetes mellitus is defined as hyperglycemia that occurs within the first month of life in term infants. It can be either permanent or transient. Cerebellar agenesis and permanent neonatal diabetes has been previously reported as a new autosomal recessive disorder. Pancreas Transcription Factor 1 Alpha (PTF1A) mutations have been related with this constellation of abnormalities. Here we report a new case of cerebellar agenesis and neonatal diabetes mellitus whose parents are PTF1A mutation carriers.

  4. Permanent neonatal diabetes mellitus caused by a novel mutation in the KCNJ11 gene.

    Science.gov (United States)

    Doneray, Hakan; Houghton, Jayne; Tekgunduz, Kadir Serafettin; Balkir, Ferat; Caner, Ibrahim

    2014-03-01

    Mutations in the KCNJ11 gene are responsible for the majority of permanent neonatal diabetes mellitus (PNDM) cases. Some mutations in this gene, including p.Q52R, are associated with the developmental delay, epilepsy, neonatal diabetes (DEND) syndrome. We describe a patient with PNDM who had no neurological finding although she was determined to have a novel mutation (p.Q52L) in the same residue of the KCNJ11 as in the previously reported cases with DEND syndrome. This case suggests that not all Q52 mutations in the KCNJ11 gene are necessarily related to DEND syndrome.

  5. Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis.

    Science.gov (United States)

    Garin, Intza; Edghill, Emma L; Akerman, Ildem; Rubio-Cabezas, Oscar; Rica, Itxaso; Locke, Jonathan M; Maestro, Miguel Angel; Alshaikh, Adnan; Bundak, Ruveyde; del Castillo, Gabriel; Deeb, Asma; Deiss, Dorothee; Fernandez, Juan M; Godbole, Koumudi; Hussain, Khalid; O'Connell, Michele; Klupa, Thomasz; Kolouskova, Stanislava; Mohsin, Fauzia; Perlman, Kusiel; Sumnik, Zdenek; Rial, Jose M; Ugarte, Estibaliz; Vasanthi, Thiruvengadam; Johnstone, Karen; Flanagan, Sarah E; Martínez, Rosa; Castaño, Carlos; Patch, Ann-Marie; Fernández-Rebollo, Eduardo; Raile, Klemens; Morgan, Noel; Harries, Lorna W; Castaño, Luis; Ellard, Sian; Ferrer, Jorge; Perez de Nanclares, Guiomar; Hattersley, Andrew T

    2010-02-16

    Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs. -2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man.

  6. Neonatal diabetes in an infant of diabetic mother: same novel INS missense mutation in the mother and her offspring.

    Science.gov (United States)

    Ozturk, Mehmet Adnan; Kurtoglu, Selim; Bastug, Osman; Korkmaz, Levent; Daar, Ghaniya; Memur, Seyma; Halis, Hulya; Günes, Tamer; Hussain, Khalid; Ellard, Sian

    2014-07-01

    Neonatal diabetes is defined as an uncontrolled hyperglycemic state occurring within the first 6 months of life. It is a rare disease with an incidence of 1 to 90,000-250,000. It is usually a disease of genetic origin in which insulin gene mutations play the main role in the disease process. A baby, born to a mother who had previously been diagnosed with type 1 diabetes mellitus at 14 months of age, had a high blood sugar level within the first few hours after birth and was subsequently diagnosed as having neonatal diabetes mellitus. Baby and mother were identified as having a novel heterozygous insulin missense mutation, p.C109R. Difficulties occurred in both follow-up and feeding of the baby. Without the addition of the mother's milk, an appropriate calorie milk formula and isophane insulin were used for the baby during follow-up. Multiple mechanisms are responsible in the pathogenesis of neonatal diabetes mellitus. Insulin gene mutations are one of the factors in the development of neonatal diabetes mellitus. If a resistant hyperglycemic state persists for a long time among babies, especially in those with intrauterine growth retardation whose mothers are diabetic, the baby concerned should be followed-up carefully for the development of neonatal diabetes mellitus.

  7. Permanent neonatal diabetes caused by a novel mutation in the INS gene.

    Science.gov (United States)

    Catli, Gonul; Abaci, Ayhan; Flanagan, Sarah E; Anik, Ahmet; Ellard, Sian; Bober, Ece

    2013-01-01

    Neonatal diabetes mellitus (DM) is a rare condition that can be either transient or permanent. In this case report, we describe a novel mutation (p.L30Q) in the INS gene resulting in permanent DM in a four-month-old female who presented with polyphagia, polyuria, irritability, and hyperglycemia with glucosuria and ketonuria without acidosis.

  8. A family with permanent neonatal diabetes due to a novel mutation in INS gene.

    Science.gov (United States)

    Dimova, Rumyana; Tankova, Tsvetalina; Gergelcheva, Ivelina; Tournev, Ivailo; Konstantinova, Maya

    2015-05-01

    In this report we present a family with permanent neonatal diabetes, heterozygous for a novel INS gene missense mutation, p.A24V, manifested with marked hyperglycemia and ketoacidosis, unstable glycemic control, requiring insulin therapy, rapid progression of long-term complications and accompanying physical pathological signs and brain lesions.

  9. [Permanent neonatal diabetes and recessive mutation in the INS gene: a familial history].

    Science.gov (United States)

    Di Benedetto, M; Richard, O; Pélissier, P; Darteyre, S; Cavé, H; Stéphan, J-L

    2013-02-01

    Permanent neonatal diabetes mellitus is a rare disorder usually presenting within the first few weeks or months of life and defined by chronic hyperglycemia due to severe nonautoimmune insulin deficiency. Nonsyndromic neonatal diabetes is genetically heterogeneous and several genes have been linked to this disorder. Here, we report on a new homozygous recessive mutation in the INS gene in 2 siblings born to consanguineous parents and diagnosed with permanent neonatal diabetes without extrapancreatic features. Their clinically unaffected parents were heterozygous. Their phenotype was also characterized by severe intrauterine growth retardation, most likely reflecting severe insulin deficiency in prenatal life, hyperglycemia, and moderate dehydration in the first few days of life. Their clinical course was uneventful after introduction of insulin therapy with catch-up growth and acquisition of normal developmental milestones.

  10. Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood

    National Research Council Canada - National Science Library

    Edghill, Emma L; Flanagan, Sarah E; Patch, Ann-Marie; Boustred, Chris; Parrish, Andrew; Shields, Beverley; Shepherd, Maggie H; Hussain, Khalid; Kapoor, Ritika R; Malecki, Maciej; MacDonald, Michael J; Støy, Julie; Steiner, Donald F; Philipson, Louis H; Bell, Graeme I; Hattersley, Andrew T; Ellard, Sian

    2008-01-01

    ...). We aimed to determine the prevalence, genetics, and clinical phenotype of INS mutations in large cohorts of patients with neonatal diabetes and permanent diabetes diagnosed in infancy, childhood, or adulthood...

  11. Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus

    DEFF Research Database (Denmark)

    Colombo, Carlo; Porzio, Ottavia; Liu, Ming;

    2008-01-01

    Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation...... in the Ins2 gene exhibits PNDM associated with pancreatic beta cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset...... of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM....

  12. The molecular mechanisms and pharmacotherapy of ATP-sensitive potassium channel gene mutations underlying neonatal diabetes

    Directory of Open Access Journals (Sweden)

    Veronica Lang

    2010-11-01

    Full Text Available Veronica Lang, Peter E LightDepartment of Pharmacology and Alberta Diabetes Institute, Faculty of Medicine and Dentistry, School of Molecular and Systems Medicine, University of Alberta, Edmonton, Alberta, CanadaAbstract: Neonatal diabetes mellitus (NDM is a monogenic disorder caused by mutations in genes involved in regulation of insulin secretion from pancreatic β-cells. Mutations in the KCNJ11 and ABCC8 genes, encoding the adenosine triphosphate (ATP-sensitive potassium (KATP channel Kir6.2 and SUR1 subunits, respectively, are found in ~50% of NDM patients. In the pancreatic β-cell, KATP channel activity couples glucose metabolism to insulin secretion via cellular excitability and mutations in either KCNJ11 or ABCC8 genes alter KATP channel activity, leading to faulty insulin secretion. Inactivation mutations decrease KATP channel activity and stimulate excessive insulin secretion, leading to hyperinsulinism of infancy. In direct contrast, activation mutations increase KATP channel activity, resulting in impaired insulin secretion, NDM, and in severe cases, developmental delay and epilepsy. Many NDM patients with KCNJ11 and ABCC8 mutations can be successfully treated with sulfonylureas (SUs that inhibit the KATP channel, thus replacing the need for daily insulin injections. There is also strong evidence indicating that SU therapy ameliorates some of the neurological defects observed in patients with more severe forms of NDM. This review focuses on the molecular and cellular mechanisms of mutations in the KATP channel that underlie NDM. SU pharmacogenomics is also discussed with respect to evaluating whether patients with certain KATP channel activation mutations can be successfully switched to SU therapy.Keywords: neonatal diabetes, KCNJ11, ABCC8, ATP-sensitive potassium channels

  13. Transient neonatal diabetes mellitus caused by a de novo ABCC8 gene mutation

    Directory of Open Access Journals (Sweden)

    Jung Hyun Kong

    2011-04-01

    Full Text Available Transient neonatal diabetes mellitus (TNDM is a rare form of diabetes mellitus that presents within the first 6 months of life with remission in infancy or early childhood. TNDM is mainly caused by anomalies in the imprinted region on chromosome 6q24; however, recently, mutations in the ABCC8 gene, which encodes sulfonylurea receptor 1 (SUR1, have also been implicated in TNDM. Herein, we present the case of a male child with TNDM whose mutational analysis revealed a heterozygous c.3547C>T substitution in the ABCC8 gene, leading to an Arg1183Trp mutation in the SUR1 protein. The parents were clinically unaffected and did not show a mutation in the ABCC8 gene. This is the first case of a de novo ABCC8 gene mutation in a Korean patient with TNDM. The patient was initially treated with insulin and successfully switched to sulfonylurea therapy at 14 months of age. Remission of diabetes had occurred at the age of 16 months. Currently, the patient is 21 months old and is euglycemic without any insulin or oral hypoglycemic agents. His growth and physical development are normal, and there are no delays in achieving neurological and developmental milestones.

  14. KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes.

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    Massa, Ornella; Iafusco, Dario; D'Amato, Elena; Gloyn, Anna L; Hattersley, Andrew T; Pasquino, Bruno; Tonini, Giorgio; Dammacco, Francesco; Zanette, Giorgio; Meschi, Franco; Porzio, Ottavia; Bottazzo, Gianfranco; Crinó, Antonino; Lorini, Renata; Cerutti, Franco; Vanelli, Maurizio; Barbetti, Fabrizio

    2005-01-01

    Permanent neonatal diabetes mellitus (PNDM) is a rare condition characterized by severe hyperglycemia constantly requiring insulin treatment from its onset. Complete deficiency of glucokinase (GCK) can cause PNDM; however, the genetic etiology is unknown in most PNDM patients. Recently, heterozygous activating mutations of KCNJ11, encoding Kir6.2, the pore forming subunit of the ATP-dependent potassium (K(ATP)) channel of the pancreatic beta-cell, were found in patients with PNDM. Closure of the K(ATP) channel exerts a pivotal role in insulin secretion by modifying the resting membrane potential that leads to insulin exocytosis. We screened the KCNJ11 gene in 12 Italian patients with PNDM (onset within 3 months from birth) and in six patients with non-autoimmune, insulin-requiring diabetes diagnosed during the first year of life. Five different heterozygous mutations were identified: c.149G>C (p.R50P), c.175G>A (p.V59M), c.509A>G (p.K170R), c.510G>C (p.K170N), and c.601C>T (p.R201C) in eight patients with diabetes diagnosed between day 3 and 182. Mutations at Arg50 and Lys170 residues are novel. Four patients also presented with motor and/or developmental delay as previously reported. We conclude that KCNJ11 mutations are a common cause of PNDM either in isolation or associated with developmental delay. Permanent diabetes of non autoimmune origin can present up to 6 months from birth in individuals with KCNJ11 and EIF2AK3 mutations. Therefore, we suggest that the acronym PNDM be replaced with the more comprehensive permanent diabetes mellitus of infancy (PDMI), linking it to the gene product (e.g., GCK-PDMI, KCNJ11-PDMI) to avoid confusion between patients with early-onset, autoimmune type 1 diabetes.

  15. Permanent neonatal diabetes by a new mutation in KCNJ11: unsuccessful switch to sulfonylurea.

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    Lau, Eva; Correia, Cintia; Freitas, Paula; Nogueira, Claúdia; Costa, Maria; Saavedra, Ana; Costa, Carla; Carvalho, Davide; Fontoura, Manuel

    2015-12-01

    Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (KATP). Sulfonylureas promote KATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene - KCNJ11:c1001G>7 (p.Gly334Val) - and confirmed the diagnosis of PNDM. Therefore it was attempted to switch from insulin therapy to sulfonylurea. During glibenclamide institution C-peptide levels increased, however the suboptimal glycemic control lead us to restart an intensive insulin scheme. This new variant of KCNJ11 mutation had a phenotypic lack of response to sulfonylurea therapy. Age, prior poor metabolic control and functional change of KATP channel induced by this specific mutation may explain the observed unsuccessful switch to sulfonylurea. Interestingly, C-peptide levels raise during glibenclamide administration support some degree of improvement in insulin secretory capacity induced by the treatment. Understanding the response to sulfonylurea is crucial as successful treatment may be life-changing in these patients.

  16. Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus.

    Science.gov (United States)

    Colombo, Carlo; Porzio, Ottavia; Liu, Ming; Massa, Ornella; Vasta, Mario; Salardi, Silvana; Beccaria, Luciano; Monciotti, Carla; Toni, Sonia; Pedersen, Oluf; Hansen, Torben; Federici, Luca; Pesavento, Roberta; Cadario, Francesco; Federici, Giorgio; Ghirri, Paolo; Arvan, Peter; Iafusco, Dario; Barbetti, Fabrizio

    2008-06-01

    Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation in the Ins2 gene exhibits PNDM associated with pancreatic beta cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset, but rapidly declined over time. When these mutant proinsulins were expressed in HEK293 cells, we observed defects in insulin protein folding and secretion. In these experiments, expression of the mutant proinsulins was also associated with increased Grp78 protein expression and XBP1 mRNA splicing, 2 markers of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM.

  17. Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57

    DEFF Research Database (Denmark)

    Bak, Mads; Boonen, Susanne E; Dahl, Christina

    2016-01-01

    of developing diabetes mellitus type 2 later in life. Transient neonatal diabetes mellitus 1 is caused by overexpression of the maternally imprinted genes PLAGL1 and HYMAI on chromosome 6q24. One of the mechanisms leading to overexpression of the locus is hypomethylation of the maternal allele of PLAGL1......BACKGROUND: Transient neonatal diabetes mellitus 1 (TNDM1) is a rare imprinting disorder characterized by intrautering growth retardation and diabetes mellitus usually presenting within the first six weeks of life and resolves by the age of 18 months. However, patients have an increased risk...... and HYMAI. A subset of patients with maternal hypomethylation at PLAGL1 have hypomethylation at additional imprinted loci throughout the genome, including GRB10, ZIM2 (PEG3), MEST (PEG1), KCNQ1OT1 and NESPAS (GNAS-AS1). About half of the TNDM1 patients carry mutations in ZFP57, a transcription factor...

  18. Permanent neonatal diabetes mellitus due to KCNJ11 mutation in a Portuguese family: transition from insulin to oral sulfonylureas.

    Science.gov (United States)

    Dupont, Juliette; Pereira, Carla; Medeira, Ana; Duarte, Rui; Ellard, Sian; Sampaio, Lurdes

    2012-01-01

    Permanent neonatal diabetes mellitus (PNDM) is a rare form of diabetes diagnosed within the first 6 months of life. Heterozygous activation mutations in KCNJ11, encoding the Kir6.2 subunit of the ATP-sensitive potassium (K(ATP)) channel, which acts as a key role in insulin secretion regulation, account for about half of the cases of PNDM. The majority of the patients represent isolated cases resulting from de novo mutations. Approximately 20% have associated neurologic features: the most severe form, which includes epilepsy and developmental delay, is called developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome and the milder form, with less severe developmental delay and without epilepsy, is designated intermediate DEND syndrome. Individuals with KCNJ11 mutations have been successfully transitioned from insulin to sulfonylurea (SU) therapy. Furthermore, there have been cases reported with variable improvement in neurological function following a successful switching. We describe a 12-year-old Portuguese girl with PNDM due to the previously reported R201C mutation in the KCNJ11 gene. Her medical history includes prematurity and moderate developmental delay. The mutation was inherited from her mother who has isolated PNDM. The patient was successfully transferred from insulin to SU, whereas her mother showed SU resistance. Despite good glycemic control, no improvements in the cognitive performance were verified. We present our experience in switching treatment from insulin to oral SUs in this family, and also discuss whether or not the girl's developmental delay is related with the Kir6.2 mutation. To our knowledge, this is the first Portuguese patient reported with successful transition to SU treatment.

  19. Permanent neonatal diabetes in siblings with novel C109Y INS mutation transmitted by an unaffected parent with somatic mosaicism.

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    Bee, Yong Mong; Zhao, Yi; Ellard, Sian; Hattersley, Andrew T; Yap, Fabian

    2014-06-01

    Mutations involving the insulin (INS) gene are a common cause of permanent neonatal diabetes (PND). Although INS mutations typically occur de novo and germline INS mutations transmitted to offspring by unaffected parents has been described, somatic mosaicism in a parent with an INS mutation has not been previously reported. We describe two siblings (one brother and one sister) with PND (26- and 19-yr old diagnosed at 3 and 7 months old, respectively), whose parents were unaffected. We performed genetic analysis of leukocyte DNA for this family. Both patients were found to carry the novel heterozygous c.326G>A substitution in exon 3 of INS, resulting in a p.C109Y change of the insulin protein. Analyses of leukocyte DNA from the parents revealed low level mutation in the sequencing trace of the father, raising the possibility of somatic mosaicism. Real-time polymerase chain reaction (PCR) analysis showed he had approximately 73% of the mutant allele relative to his affected son. This first report of somatic mosaicism in an unaffected parent with an INS mutation suggests that parental mosaicism may be responsible for the transmission of PND in patients with de novo INS mutations. As such, appropriate counseling for recurrent risks should be considered and we recommend that molecular genetic testing for future siblings at birth should be offered to the parents of children with INS mutation.

  20. Microcephaly, epilepsy, and neonatal diabetes due to compound heterozygous mutations in IER3IP1: insights into the natural history of a rare disorder.

    Science.gov (United States)

    Shalev, Stavit A; Tenenbaum-Rakover, Yardena; Horovitz, Yoseph; Paz, Veronica P; Ye, Honggang; Carmody, David; Highland, Heather M; Boerwinkle, Eric; Hanis, Craig L; Muzny, Donna M; Gibbs, Richard A; Bell, Graeme I; Philipson, Louis H; Greeley, Siri Atma W

    2014-05-01

    Neonatal diabetes mellitus is known to have over 20 different monogenic causes. A syndrome of permanent neonatal diabetes along with primary microcephaly with simplified gyral pattern associated with severe infantile epileptic encephalopathy was recently described in two independent reports in which disease-causing homozygous mutations were identified in the immediate early response-3 interacting protein-1 (IER3IP1) gene. We report here an affected male born to a non-consanguineous couple who was noted to have insulin-requiring permanent neonatal diabetes, microcephaly, and generalized seizures. He was also found to have cortical blindness, severe developmental delay and numerous dysmorphic features. He experienced a slow improvement but not abrogation of seizure frequency and severity on numerous anti-epileptic agents. His clinical course was further complicated by recurrent respiratory tract infections and he died at 8 years of age. Whole exome sequencing was performed on DNA from the proband and parents. He was found to be a compound heterozygote with two different mutations in IER3IP1: p.Val21Gly (V21G) and a novel frameshift mutation p.Phe27fsSer*25. IER3IP1 is a highly conserved protein with marked expression in the cerebral cortex and in beta cells. This is the first reported case of compound heterozygous mutations within IER3IP1 resulting in neonatal diabetes. The triad of microcephaly, generalized seizures, and permanent neonatal diabetes should prompt screening for mutations in IER3IP1. As mutations in genes such as NEUROD1 and PTF1A could cause a similar phenotype, next-generation sequencing approaches-such as exome sequencing reported here-may be an efficient means of uncovering a diagnosis in future cases.

  1. Medical and developmental impact of transition from subcutaneous insulin to oral glyburide in a 15-yr-old boy with neonatal diabetes mellitus and intermediate DEND syndrome: extending the age of KCNJ11 mutation testing in neonatal DM.

    Science.gov (United States)

    Mohamadi, Ali; Clark, Loretta M; Lipkin, Paul H; Mahone, E Mark; Wodka, Ericka L; Plotnick, Leslie P

    2010-05-01

    Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-sensitive potassium channel, often result in neonatal diabetes. Patients with this mutation have been successfully transitioned from insulin to sulfonylurea (SU) therapy without compromise in their glycemic control. Among patients with neonatal diabetes due to KCNJ11 mutations, approximately 25% have neurological findings including developmental delay, motor dysfunction, and epilepsy, known as DEND syndrome. There have been rare cases of juvenile patients with intermediate DEND syndrome (iDEND) reporting variable improvement in neurological function following transition from insulin to SU treatment. We describe the response to glyburide in a 15-yr-old boy with severe global developmental delays resulting from the KCNJ11 mutation V59M. The patient was discovered to have diabetes mellitus at 11.5 months of age, making this the oldest age at diagnosis of a KCNJ11 mutation-related case of neonatal diabetes. Because consensus has been to screen patients for this mutation only if younger than 6 months at the time of diagnosis, we suggest that all patients under the age of 12 months at diagnosis should receive genetic testing for monogenic causes of diabetes.

  2. Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism.

    Science.gov (United States)

    Senée, Valérie; Chelala, Claude; Duchatelet, Sabine; Feng, Daorong; Blanc, Hervé; Cossec, Jack-Christophe; Charon, Céline; Nicolino, Marc; Boileau, Pascal; Cavener, Douglas R; Bougnères, Pierre; Taha, Doris; Julier, Cécile

    2006-06-01

    We recently described a new neonatal diabetes syndrome associated with congenital hypothyroidism, congenital glaucoma, hepatic fibrosis and polycystic kidneys. Here, we show that this syndrome results from mutations in GLIS3, encoding GLI similar 3, a recently identified transcription factor. In the original family, we identified a frameshift mutation predicted to result in a truncated protein. In two other families with an incomplete syndrome, we found that affected individuals harbor deletions affecting the 11 or 12 5'-most exons of the gene. The absence of a major transcript in the pancreas and thyroid (deletions from both families) and an eye-specific transcript (deletion from one family), together with residual expression of some GLIS3 transcripts, seems to explain the incomplete clinical manifestations in these individuals. GLIS3 is expressed in the pancreas from early developmental stages, with greater expression in beta cells than in other pancreatic tissues. These results demonstrate a major role for GLIS3 in the development of pancreatic beta cells and the thyroid, eye, liver and kidney.

  3. Early-onset, severe lipoatrophy in a patient with permanent neonatal diabetes mellitus secondary to a recessive mutation in the INS gene.

    Science.gov (United States)

    Rachmiel, Marianna; Rubio-Cabezas, Oscar; Ellard, Sian; Hattersley, Andrew T; Perlman, Kusiel

    2012-09-01

    We describe a case of neonatal diabetes due to a homozygous mutation (c.3 G>T) at the INS gene, leading to lack of insulin expression and severe hyperglycemia from day one of life requiring permanent insulin replacement therapy. The genetic loss of endogenous insulin production likely led to lack of immune tolerance to insulin, with resultant autoantibody production against exogenous insulin and progressive immune-mediated lipoatrophy at injection sites.

  4. Disruption of a Novel Krüppel-like Transcription Factor p300-regulated Pathway for Insulin Biosynthesis Revealed by Studies of the c.-331 INS Mutation Found in Neonatal Diabetes Mellitus*

    OpenAIRE

    2011-01-01

    Krüppel-like transcription factors (KLFs) have elicited significant attention because of their regulation of essential biochemical pathways and, more recently, because of their fundamental role in the mechanisms of human diseases. Neonatal diabetes mellitus is a monogenic disorder with primary alterations in insulin secretion. We here describe a key biochemical mechanism that underlies neonatal diabetes mellitus insulin biosynthesis impairment, namely a homozygous mutation within the insulin ...

  5. Visuomotor Performance in KCNJ11-Related Neonatal Diabetes Is Impaired in Children With DEND-Associated Mutations and May Be Improved by Early Treatment With Sulfonylureas

    Science.gov (United States)

    Shah, Reshma P.; Spruyt, Karen; Kragie, Brigette C.; Greeley, Siri Atma W.; Msall, Michael E.

    2012-01-01

    OBJECTIVE To assess performance on an age-standardized neuromotor coordination task among sulfonylurea-treated KCNJ11-related neonatal diabetic patients. RESEARCH DESIGN AND METHODS Nineteen children carrying KCNJ11 mutations associated with isolated diabetes (R201H; n = 8), diabetes with neurodevelopmental impairment (V59M or V59A [V59M/A]; n = 8), or diabetes not consistently associated with neurodevelopmental disability (Y330C, E322K, or R201C; n = 3) were studied using the age-standardized Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI). RESULTS Although R201H subjects tested in the normal range (median standard score = 107), children with V59M/A mutations had significantly lower than expected VMI standard scores (median = 49). The scores for all three groups were significantly different from each other (P = 0.0017). The age of sulfonylurea initiation was inversely correlated with VMI scores in the V59M/A group (P < 0.05). CONCLUSIONS Neurodevelopmental disability in KCNJ11-related diabetes includes visuomotor problems that may be ameliorated by early sulfonylurea treatment. Comprehensive longitudinal assessment on larger samples will be imperative. PMID:22855734

  6. Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy.

    Science.gov (United States)

    Sagen, Jørn V; Raeder, Helge; Hathout, Eba; Shehadeh, Naim; Gudmundsson, Kolbeinn; Baevre, Halvor; Abuelo, Dianne; Phornphutkul, Chanika; Molnes, Janne; Bell, Graeme I; Gloyn, Anna L; Hattersley, Andrew T; Molven, Anders; Søvik, Oddmund; Njølstad, Pål R

    2004-10-01

    Permanent neonatal diabetes (PND) can be caused by mutations in the transcription factors insulin promoter factor (IPF)-1, eukaryotic translation initiation factor-2alpha kinase 3 (EIF2AK3), and forkhead box-P3 and in key components of insulin secretion: glucokinase (GCK) and the ATP-sensitive K(+) channel subunit Kir6.2. We sequenced the gene encoding Kir6.2 (KCNJ11) in 11 probands with GCK-negative PND. Heterozygous mutations were identified in seven probands, causing three novel (F35V, Y330C, and F333I) and two known (V59M and R201H) Kir6.2 amino acid substitutions. Only two probands had a family history of diabetes. Subjects with the V59M mutation had neurological features including motor delay. Three mutation carriers tested had an insulin secretory response to tolbutamide, but not to glucose or glucagon. Glibenclamide was introduced in increasing doses to investigate whether sulfonylurea could replace insulin. At a glibenclamide dose of 0.3-0.4 mg. kg(-1). day(-1), insulin was discontinued. Blood glucose did not deteriorate, and HbA(1c) was stable or fell during 2-6 months of follow-up. An oral glucose tolerance test performed in one subject revealed that glucose-stimulated insulin release was restored. Mutations in Kir6.2 were the most frequent cause of PND in our cohort. Apparently insulin-dependent patients with mutations in Kir6.2 may be managed on an oral sulfonylurea with sustained metabolic control rather than insulin injections, illustrating the principle of pharmacogenetics applied in diabetes treatment.

  7. [Permanent neonatal diabetes with known genetic background: oral drugs in treatment of childhood diabetes].

    Science.gov (United States)

    Gach, Agnieszka; Gadzicka, Anna; Młynarski, Wojciech

    2008-01-01

    Diabetes, which is diagnosed before 6 months of age, is patogenetically different than type 1 diabetes. This kind of diabetes also known as a neonatal diabetes is genetically determined with monogenic mode of inheritance. Most of these patients are carriers of heterozygous mutation in the KCNJ11 or ABCC8 gene. These mutations may activate the Kir6.2/SUR1 potassium channel in the beta cells and disturb insulin secretion, which in consequence leads to diabetes. This patological phenomenon is reversible if sulfonylureas are used as a first line therapy. In the current paper a systematic review of clinical aspects of sulfonylurea treatment in neonatal diabetes has been performed. This gives the further evidence that knowlegde of the patogenesis of neonatal diabetes may be easily transferred to bedside and clinical practice.

  8. Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY)

    DEFF Research Database (Denmark)

    Boesgaard, Trine W; Pruhova, Stepanka; Andersson, Ehm A

    2010-01-01

    Insulin gene (INS) mutations have recently been described as a common cause of permanent neonatal diabetes (PNDM) and a rare cause of diabetes diagnosed in childhood or adulthood.......Insulin gene (INS) mutations have recently been described as a common cause of permanent neonatal diabetes (PNDM) and a rare cause of diabetes diagnosed in childhood or adulthood....

  9. Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57

    DEFF Research Database (Denmark)

    Bak, Mads; Boonen, Susanne E; Dahl, Christina;

    2016-01-01

    involved in establishment and maintenance of methylation of imprinted loci. Our objective was to investigate whether additional regions are aberrantly methylated in ZFP57 mutation carriers. METHODS: Genome-wide DNA methylation analysis was performed on four individuals with homozygous or compound...... and HYMAI. A subset of patients with maternal hypomethylation at PLAGL1 have hypomethylation at additional imprinted loci throughout the genome, including GRB10, ZIM2 (PEG3), MEST (PEG1), KCNQ1OT1 and NESPAS (GNAS-AS1). About half of the TNDM1 patients carry mutations in ZFP57, a transcription factor...

  10. Improved motor development and good long-term glycaemic control with sulfonylurea treatment in a patient with the syndrome of intermediate developmental delay, early-onset generalised epilepsy and neonatal diabetes associated with the V59M mutation in the KCNJ11 gene

    NARCIS (Netherlands)

    Slingerland, A. S.; Nuboer, R.; Hadders-Algra, M.; Hattersley, A. T.; Bruining, G. J.

    2006-01-01

    Aims/hypothesis Activating mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the K-ATP channels in pancreatic beta cells are a common cause of neonatal diabetes. One-third of patients also have developmental delay, which probably results from mutated K-ATP channels in muscle, nerve and bra

  11. Disruption of a novel Kruppel-like transcription factor p300-regulated pathway for insulin biosynthesis revealed by studies of the c.-331 INS mutation found in neonatal diabetes mellitus.

    Science.gov (United States)

    Bonnefond, Amélie; Lomberk, Gwen; Buttar, Navtej; Busiah, Kanetee; Vaillant, Emmanuel; Lobbens, Stéphane; Yengo, Loïc; Dechaume, Aurélie; Mignot, Brigitte; Simon, Albane; Scharfmann, Raphaël; Neve, Bernadette; Tanyolaç, Sinan; Hodoglugil, Ugur; Pattou, François; Cavé, Hélène; Iovanna, Juan; Stein, Roland; Polak, Michel; Vaxillaire, Martine; Froguel, Philippe; Urrutia, Raul

    2011-08-12

    Krüppel-like transcription factors (KLFs) have elicited significant attention because of their regulation of essential biochemical pathways and, more recently, because of their fundamental role in the mechanisms of human diseases. Neonatal diabetes mellitus is a monogenic disorder with primary alterations in insulin secretion. We here describe a key biochemical mechanism that underlies neonatal diabetes mellitus insulin biosynthesis impairment, namely a homozygous mutation within the insulin gene (INS) promoter, c.-331C>G, which affects a novel KLF-binding site. The combination of careful expression profiling, electromobility shift assays, reporter experiments, and chromatin immunoprecipitation demonstrates that, among 16 different KLF proteins tested, KLF11 is the most reliable activator of this site. Congruently, the c.-331C>G INS mutation fails to bind KLF11, thus inhibiting activation by this transcription factor. Klf11(-/-) mice recapitulate the disruption in insulin production and blood levels observed in patients. Thus, these data demonstrate an important role for KLF11 in the regulation of INS transcription via the novel c.-331 KLF site. Lastly, our screening data raised the possibility that other members of the KLF family may also regulate this promoter under distinct, yet unidentified, cellular contexts. Collectively, this study underscores a key role for KLF proteins in biochemical mechanisms of human diseases, in particular, early infancy onset diabetes mellitus.

  12. Oral desmopressin in neonatal diabetes insipidus.

    OpenAIRE

    Stick, S M; Betts, P R

    1987-01-01

    A neonate with cranial diabetes insipidus was successfully treated with oral desmopressin. The patient had a midline cleft lip and palate and we obtained a more consistent response using the oral route than using the usual nasal route.

  13. Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-Onset Diabetes of the Young

    Science.gov (United States)

    ... Diabetes Monogenic Forms of Diabetes Monogenic Forms of Diabetes The most common forms of diabetes, type 1 ... is inherited from each parent. Monogenic Forms of Diabetes Some rare forms of diabetes result from mutations ...

  14. Diabetes mellitus neonatal en Costa Rica

    Directory of Open Access Journals (Sweden)

    Francis Ruiz-Salazar

    2014-09-01

    Full Text Available La diabetes mellitus neonatal es un raro desorden metabólico usualmente desarrollado en las primeras 6 semanas de vida, secundario a un grupo de mutaciones y defectos del desarrollo pancreático que puede desembocar en una catástrofe clínica si no se identifica tempranamente; se divide en una variante transitoria y una permanente, siendo la primera la más frecuente, con cerca de un 60% de los casos. El manejo inicial de ambas variantes es la insulinoterapia intensiva, que en la variante transitoria puede suspenderse usualmente en los primeros meses de vida. El síndrome de disregulación inmunológica, poliendocrinopatía y enteropatía ligada a X (IPEX por sus siglas en inglés, es una causa extremadamente rara de la variante permanente, casi siempre mortal, caracterizada por un inmunocompromiso severo, enteropatía, diabetes y dermatitis. En el estudio se describen 4 casos de diabetes mellitus neonatal diagnosticados en el Hospital Nacional de Niños de San José, Costa Rica: 2 correspondientes a una diabetes mellitus neonatal transitoria, 2 a una diabetes mellitus neonatal permanente y 1 de ellos correspondiente a un síndrome de IPEX.

  15. Transient neonatal diabetes, ZFP57, and hypomethylation of multiple imprinted loci

    DEFF Research Database (Denmark)

    Boonen, Susanne E; Mackay, Deborah J G; Hahnemann, Johanne M D

    2013-01-01

    Transient neonatal diabetes mellitus 1 (TNDM1) is the most common cause of diabetes presenting at birth. Approximately 5% of the cases are due to recessive ZFP57 mutations, causing hypomethylation at the TNDM locus and other imprinted loci (HIL). This has consequences for patient care because...

  16. PPARγ mutations, lipodystrophy and diabetes.

    Science.gov (United States)

    Astapova, Olga; Leff, Todd

    2014-11-01

    The focus of this review is the lipodystrophy syndrome caused by mutation in the PPARγ nuclear receptor - partial familial lipodystrophy FPLD3. To provide a broader context for how these mutations act to generate the clinical features of partial lipodystrophy we will review the basic biology of PPARγ and also survey the set PPARγ genetic variants that do not cause lipodystrophy, but are nonetheless associated with clinically related syndromes, specifically type 2 diabetes.

  17. Neonatal diabetes mellitus: a disease linked to multiple mechanisms

    Directory of Open Access Journals (Sweden)

    Cavé Hélène

    2007-03-01

    Full Text Available Abstract Transient (TNDM and Permanent (PNDM Neonatal Diabetes Mellitus are rare conditions occurring in 1:300,000–400,000 live births. TNDM infants develop diabetes in the first few weeks of life but go into remission in a few months, with possible relapse to a permanent diabetes state usually around adolescence or as adults. The pancreatic dysfunction in this condition may be maintained throughout life, with relapse initiated at times of metabolic stress such as puberty or pregnancy. In PNDM, insulin secretory failure occurs in the late fetal or early post-natal period and does not go into remission. Patients with TNDM are more likely to have intrauterine growth retardation and less likely to develop ketoacidosis than patients with PNDM. In TNDM, patients are younger at the diagnosis of diabetes and have lower initial insulin requirements. Considerable overlap occurs between the two groups, so that TNDM cannot be distinguished from PNDM based on clinical features. Very early onset diabetes mellitus seems to be unrelated to autoimmunity in most instances. A number of conditions are associated with PNDM, some of which have been elucidated at the molecular level. Among these, the very recently elucidated mutations in the KCNJ11 and ABCC8 genes, encoding the Kir6.2 and SUR1 subunit of the pancreatic KATP channel involved in regulation of insulin secretion, account for one third to half of the PNDM cases. Molecular analysis of chromosome 6 anomalies (found in more than 60% in TNDM, and the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1, provides a tool to identify TNDM from PNDM in the neonatal period. This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 genes, from insulin therapy to sulfonylureas. Recurrent diabetes is common in patients with "transient" neonatal diabetes mellitus and, consequently, prolonged follow-up is imperative. Realizing how

  18. Novel homozygous likely-pathogenic intronic variant in INS causing permanent neonatal diabetes in siblings.

    Science.gov (United States)

    Courtney, Rachel; Gamble, Candace; Arango, Monica L; Shah, Avni; Rubio, Nunilo I; Nguyen, Joanne; Rodriguez-Buritica, David

    2016-09-01

    Permanent neonatal diabetes (PNDM) is a rare genetic condition characterized by hyperglycemia, insulinopenia, and failure to thrive beginning in the first 6 months of life. Recessive mutations in INS lead to decreased production of insulin via a variety of mechanisms. We present a case of two brothers, born to consanguineous parents, with a novel homozygous intronic variant in the INS gene. Each patient presented with intrauterine growth restriction (IUGR) and significant hyperglycemia within the first 24 h of life. All the grandparents have a diagnosis of diabetes, one of them requiring insulin treatment and the parents currently deny personal histories of diabetes. Although this mutation has not previously been described, given the segregation of the mutation, absence of heterozygosity (AOH) in the genomic region encompassing the INS locus, documented insulinopenia, and high neonatal insulin requirements, we suspect that this variant is pathogenic. Possible implications for personalized treatment of the underlying molecular etiology for an individual's diabetes are discussed.

  19. Severe neonatal epileptic encephalopathy and KCNQ2 mutation: neuropathological substrate?

    Directory of Open Access Journals (Sweden)

    Charlotte eDalen Meurs-Van Der Schoor

    2014-12-01

    Full Text Available Background:Neonatal convulsions are clinical manifestations in a heterogeneous group of disorders with different etiology and outcome. They are attributed to several genetic causes. Methods:We describe a patient with intractable neonatal seizures who died from respiratory compromise during a status epilepticus. Results:This case report provides EEG, MRI, genetic analysis and neuropathological data. Genetic analysis revealed a de novo heterozygous missense mutation in the KCNQ2 gene, which encodes a subunit of a voltage-gated potassium channel. KCNQ2 gene mutation is associated with intractable neonatal seizures. EEG, MRI data as well as mutation analysis have been described in other KCNQ2 cases. Postmortem neuropathologic investigation revealed mild malformation of cortical development with increased heterotopic neurons in the deep white matter compared to an age-matched control subject. The new finding of this study is the combination of a KCNQ2 mutation and the cortical abnormalities. Conclusions:KCNQ2 mutations should be considered in neonates with refractory epilepsy of unknown cause. The mild cortical malformation is an important new finding, though it remains unknown whether these cortical abnormalities are due to the KCNQ2 mutation or are secondary to the refractory seizures.

  20. A novel phenotype of a hepatocyte nuclear factor homeobox A (HNF1A) gene mutation, presenting with neonatal cholestasis

    NARCIS (Netherlands)

    de Vries, Aleida G. M.; Bakker-van Waarde, Willie M.; Dassel, Anne C. M.; Losekoot, Monique; Duiker, Evelien W.; Gouw, Annette S. H.; Bodewes, Frank A. J. A.

    2015-01-01

    We report a novel phenotype of a hepatocyte nuclear factor homeobox A (HNF1A) mutation (heterozygote c.130dup, p.Leu44fs) presenting with transient neonatal cholestasis, subsequently followed by persistent elevation of transaminases, maturity-onset diabetes of the young (MODY) type 3 and hepatocellu

  1. Heart rate variability in neonates of type 1 diabetic pregnancy.

    Science.gov (United States)

    Russell, Noirin E; Higgins, Mary F; Kinsley, Brendan F; Foley, Michael E; McAuliffe, Fionnuala M

    2016-01-01

    Cardiomyopathy is a common finding in offspring of pre-gestational type 1 diabetic pregnancy. Echocardiographic and biochemical evidence of fetal cardiac dysfunction have also been reported. Studies suggest that offspring of diabetic mothers (ODM) undergo a fetal programming effect due to the hyperglycaemic intrauterine milieu which increases their risk of cardiovascular morbidity in adult life. Decreased neonatal heart rate variability (HRV) has been described in association with in-utero growth restriction, prematurity, sudden infant death syndrome and congenital heart disease. The effect of in-utero exposure to hyperglycaemia in diabetic pregnancy on neonatal HRV is unknown. Our aim was to determine if neonatal HRV differs between normal and diabetic pregnancy. This was a prospective observational study of 38 patients with pregestational type 1 diabetes and 26 controls. HRV assessment was performed using Powerlab (ADI Instruments Ltd). Heart rate variability assessment and cord blood sampling for pH and glucose were performed for all neonates. Maternal glycaemic control was assessed via measurement of glycosylated haemoglobin in each trimester in the diabetic cohort. Neonates of diabetic mothers had evidence of altered heart rate variability, with increased low frequency to high frequency ratio (LF: HF), suggestive of a shift towards sympathetic predominance (pheart to fluctuations in maternal glycaemia with subsequent alterations in HRV may explain why infants of diabetic mothers are at greater risk of cardiovascular disease in later life. Copyright © 2015. Published by Elsevier Ireland Ltd.

  2. Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset.

    Science.gov (United States)

    Bitoun, Marc; Bevilacqua, Jorge A; Prudhon, Bernard; Maugenre, Svetlana; Taratuto, Ana Lia; Monges, Soledad; Lubieniecki, Fabiana; Cances, Claude; Uro-Coste, Emmanuelle; Mayer, Michèle; Fardeau, Michel; Romero, Norma B; Guicheney, Pascale

    2007-12-01

    We report four heterozygous dynamin 2 (DNM2) mutations in five centronuclear myopathy patients aged 1 to 15 years. They all presented with neonatal hypotonia with weak suckling. Thereafter, their phenotype progressively improved. All patients demonstrated muscle weakness prominent in the lower limbs, and most of them also presented with facial weakness, open mouth, arched palate, ptosis, and ophthalmoparesis. Electrophysiology showed only myopathic changes, and muscle biopsies showed central nuclei and type 1 fiber hypotrophy and predominance. Our results expand the phenotypic spectrum of dynamin 2-related centronuclear myopathy from the classic mild form to the more severe neonatal phenotype.

  3. Neonatal Marfan Syndrome: Report of a Case with an Inherited Splicing Mutation outside the Neonatal Domain.

    Science.gov (United States)

    Le Gloan, Laurianne; Hauet, Quentin; David, Albert; Hanna, Nadine; Arfeuille, Chloé; Arnaud, Pauline; Boileau, Catherine; Romefort, Bénédicte; Benbrik, Nadir; Gournay, Véronique; Joram, Nicolas; Baron, Olivier; Isidor, Bertrand

    2016-02-01

    We report a child and her mother affected by Marfan syndrome. The child presented with a phenotype of neonatal Marfan syndrome, revealed by acute and refractory heart failure, finally leading to death within the first 4 months of life. Her mother had a common clinical presentation. Genetic analysis revealed an inherited FBN1 mutation. This intronic mutation (c.6163+3_6163+6del), undescribed to date, leads to exon 49 skipping, corresponding to in-frame deletion of 42 amino acids (p.Ile2014_Asp2055del). FBN1 next-generation sequencing did not show any argument for mosaicism. Association in the same family of severe neonatal and classical Marfan syndrome illustrates the intrafamilial phenotype variability.

  4. Sulfonylurea Treatment Before Genetic Testing in Neonatal Diabetes: Pros and Cons

    Science.gov (United States)

    Carmody, David; Bell, Charles D.; Hwang, Jessica L.; Dickens, Jazzmyne T.; Sima, Daniela I.; Felipe, Dania L.; Zimmer, Carrie A.; Davis, Ajuah O.; Kotlyarevska, Kateryna; Naylor, Rochelle N.; Philipson, Louis H.

    2014-01-01

    Context: Diabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental outcomes in children with KCNJ11 or ABCC8 mutations, the most common gene causes. Objective: Assess the risks and benefits of initiating sulfonylurea therapy before genetic testing results become available. Design, Setting, and Patients: Observational retrospective study of subjects with neonatal diabetes within the University of Chicago Monogenic Diabetes Registry. Main Outcome Measures: Response to sulfonylurea (determined by whether insulin could be discontinued) and treatment side effects in those treated empirically. Results: A total of 154 subjects were diagnosed with diabetes before 6 months of age. A genetic diagnosis had been determined in 118 (77%), with 73 (47%) having a mutation in KCNJ11 or ABCC8. The median time from clinical diagnosis to genetic diagnosis was 10.4 weeks (range, 1.6 to 58.2 wk). In nine probands, an empiric sulfonylurea trial was initiated within 28 days of diabetes diagnosis. A genetic cause was subsequently found in eight cases, and insulin was discontinued within 14 days of sulfonylurea initiation in all of these cases. Conclusions: Sulfonylurea therapy appears to be safe and often successful in neonatal diabetes patients before genetic testing results are available; however, larger numbers of cases must be studied. Given the potential beneficial effect on neurodevelopmental outcome, glycemic control, and the current barriers to expeditious acquisition of genetic testing, an empiric inpatient trial of sulfonylurea can be considered. However, obtaining a genetic diagnosis remains imperative to inform long-term management and prognosis. PMID:25238204

  5. Progress of neonatal diabetes mellitus%新生儿糖尿病研究进展

    Institute of Scientific and Technical Information of China (English)

    刘颖; 陶于洪

    2011-01-01

    新生儿糖尿病是一组异质性单基因遗传病,常被误诊为1型糖尿病.永久性新生儿糖尿病与免疫无关,主要与KCNJ 11、ABCC8和胰岛素基因等基因突变有关;多以酮症酸中毒起病,伴宫内发育迟缓、脱水.基因检测有助于疾病分型,并可根据不同致病基因进行靶向治疗.对于ATP敏感的K+通道基因突变的永久性新生儿糖尿病患儿可口服磺脲类降糖药(如格列苯脲)替代胰岛素治疗.%Neonatal diabetes mellitus ( NDM ),which was often misdiagnosed as type 1 diabetes in the past,is a heterogenous single-gene genetic disease.Permanent neonatal diabetes( PNDM )is mainly associated with mutation in KCNJ11,ABCC8,and insulin associated gene instead of immunity.The most common manifestation includes diabetic ketoacidosis,intrauterine growth retardation and dehydration.Gene examination contributes to the classification of NDM and corresponding targeted therapy.Oral sulfonylurea may be used in treating patients with gene mutation of ATP-sensitive K+ channel.

  6. ATP and sulfonylurea sensitivity of mutant ATP-sensitive K+ channels in neonatal diabetes: implications for pharmacogenomic therapy.

    Science.gov (United States)

    Koster, Joseph C; Remedi, Maria S; Dao, Crystal; Nichols, Colin G

    2005-09-01

    The prediction that overactivity of the pancreatic ATP-sensitive K(+) channel (K(ATP) channel) underlies reduced insulin secretion and causes a diabetic phenotype in humans has recently been borne out by genetic studies implicating "activating" mutations in the Kir6.2 subunit of K(ATP) as causal in both permanent and transient neonatal diabetes. Here we characterize the channel properties of Kir6.2 mutations that underlie transient neonatal diabetes (I182V) or more severe forms of permanent neonatal diabetes (V59M, Q52R, and I296L). In all cases, the mutations result in a significant decrease in sensitivity to inhibitory ATP, which correlates with channel "overactivity" in intact cells. Mutations can be separated into those that directly affect ATP affinity (I182V) and those that stabilize the open conformation of the channel and indirectly reduce ATP sensitivity (V59M, Q52R, and I296L). With respect to the latter group, alterations in channel gating are also reflected in a functional "uncoupling" of sulfonylurea (SU) block: SU sensitivity of I182V is similar to that of wild-type mutants, but the SU sensitivity of all gating mutants is reduced, with the I296L mutant being resistant to block by tolbutamide (

  7. Maternal fertility problems and risk for transient neonatal diabetes mellitus

    DEFF Research Database (Denmark)

    Hargreave, Marie; Kjaer, Susanne Krüger; Jørgensen, Marit Eika

    2017-01-01

    AIMS: The study of imprinting disorders in the context of infertility and its treatment is important, as studies have indicated an increased risk. In this study, we evaluated the risk of transient neonatal diabetes mellitus (TNDM), defined here as diabetes mellitus presenting within the first six...... for TNDM, after adjustment for birth year, maternal age at birth and parental history of diabetes, although this was not statistically significant (HR = 1.49; 95% CI 0.73-3.03). The risk of children born in the period 1994-2010 (a period with more comprehensive information on maternal fertility problems...

  8. Transient diabetes mellitus in a neonatal Thoroughbred foal.

    Science.gov (United States)

    Navas de Solis, Cristobal; Foreman, Jonathan H

    2010-12-01

    To describe the clinical presentation, treatment, and outcome of a neonatal foal diagnosed with transient Type 1 diabetes mellitus. A 3-day-old Thoroughbred foal presented with a 24-hour history of diarrhea and depression. Coronavirus particles were observed in the feces via electron microscopy. During hospitalization the foal developed hyperglycemia concomitantly with low insulin concentration and an adequate response to exogenous insulin therapy supported a diagnosis of Type 1 diabetes mellitus. The foal required SC insulin for 26 days, but developed complications associated with insulin therapy that resolved with appropriate care. On follow up assessment the foal was found to be a healthy euglycemic animal with normal insulin concentration at 11 months of age. To our knowledge this is the first report of Type 1 diabetes in this age group and the first report of transient neonatal diabetes mellitus in horses. Type 1 diabetes mellitus should be considered a differential diagnosis for hyperglycemia in equine neonates and that it can be transient and managed successfully. © Veterinary Emergency and Critical Care Society 2010.

  9. Neonatal Diabetes: An Expanding List of Genes Allows for Improved Diagnosis and Treatment

    Science.gov (United States)

    Naylor, Rochelle N.; Philipson, Louis H.; Bell, Graeme I.

    2011-01-01

    There has been major progress in recent years uncovering the genetic causes of diabetes presenting in the first year of life. Twenty genes have been identified to date. The most common causes accounting for the majority of cases are mutations in the genes encoding the two subunits of the ATP-sensitive potassium channel (KATP), KCNJ11 and ABCC8, and the insulin gene (INS), as well as abnormalities in chromosome 6q24. Patients with activating mutations in KCNJ11 and ABCC8 can be treated with oral sulfonylureas in lieu of insulin injections. This compelling example of personalized genetic medicine leading to improved glucose regulation and quality of life may—with continued research—be repeated for other forms of neonatal diabetes in the future. PMID:21993633

  10. A novel SNP in 3' UTR of INS gene: A case report of neonatal diabetes mellitus.

    Science.gov (United States)

    Bogari, Neda M; Rayes, Husni H; Mostafa, Fakri; Abdel-Latif, Azza M; Ramadan, Abeer; Al-Allaf, Faisal A; Taher, Mohiuddin M; Fawzy, Ahmed

    2015-09-01

    Neonatal diabetes mellitus (NDM) is a rare condition with a prevalence of 1 in 300,000 live births. We have found 3 known SNPs in 5'UTR and a novel SNP in 3' UTR in the INS gene. These SNPs were present in 9-month-old girl from Saudi Arabia and also present in the father and mother. The novel SNP we found is not present in 1000 Genome project or other databases. Further, the newly identified 3' UTR mutation in the INS gene may abolish the polyadenylation signal and result in severe RNA instability.

  11. Intrafamilial Variability of Early-Onset Diabetes due to an INS Mutation

    Directory of Open Access Journals (Sweden)

    Siri Fredheim

    2011-01-01

    Full Text Available Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS gene. Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule causing permanent neonatal diabetes. All three were diagnosed before 29 weeks of age, were born at term with near-normal birth weight, and were negative for GAD, ICA, IA-2, and IAA autoantibodies. The daily insulin requirement the first six months after diagnosis was <0.5 U kg−1 day−1 for both children. The father, insulin treated for over 40 years, has bilateral preproliferative retinopathy. Conclusions. These three cases further confirm the essential features of diabetes caused by INS mutations with proteotoxic effect. We conclude that patients with similar features must be investigated for mutations of INS gene.

  12. MORBILIDAD Y MORTALIDAD NEONATAL ASOCIADA A LA DIABETES GESTACIONAL

    OpenAIRE

    Velázquez G,Pablo; Vega M,Genaro; Martínez M,Martha Leticia

    2010-01-01

    Objetivo: Determinar la asociación de la morbilidad y mortalidad neonatal con la diabetes gestacional. Método: Estudio tipo cohortes. Se realizó un estudio en embarazadas desde diciembre de 2007 a noviembre de 2008 en el servicio de tococirugía del Hospital General Regional No. 1 de Querétaro, México, se formaron dos grupos de 71 pacientes, uno con diabetes gestacional y otro sin ella. El muestreo fue por cuota pareado por edad. En ambos grupos se midieron variables sociodemográficas, anteced...

  13. MORBILIDAD Y MORTALIDAD NEONATAL ASOCIADA A LA DIABETES GESTACIONAL

    OpenAIRE

    Velázquez G,Pablo; Vega M,Genaro; Martínez M,Martha Leticia

    2010-01-01

    Objetivo: Determinar la asociación de la morbilidad y mortalidad neonatal con la diabetes gestacional. Método: Estudio tipo cohortes. Se realizó un estudio en embarazadas desde diciembre de 2007 a noviembre de 2008 en el servicio de tococirugía del Hospital General Regional No. 1 de Querétaro, México, se formaron dos grupos de 71 pacientes, uno con diabetes gestacional y otro sin ella. El muestreo fue por cuota pareado por edad. En ambos grupos se midieron variables sociodemográficas, anteced...

  14. Genetics Home Reference: permanent neonatal diabetes mellitus

    Science.gov (United States)

    ... PubMed Ellard S, Flanagan SE, Girard CA, Patch AM, Harries LW, Parrish A, Edghill EL, Mackay DJ, Proks ... SE, Clauin S, Bellanné-Chantelot C, de Lonlay P, Harries LW, Gloyn AL, Ellard S. Update of mutations in ...

  15. Effect of maternal diabetes on gliogensis in neonatal rat hippocampus

    Science.gov (United States)

    Sadeghi, Akram; Esfandiary, Ebrahim; Hami, Javad; Khanahmad, Hossein; Hejazi, Zahra; Razavi, Shahnaz

    2016-01-01

    Background: Diabetes in pregnancy is a common metabolic disorder associated with various adverse outcomes in the offspring including impairments in attention and memory and alterations in social behavior. Glial cells are proven to have a critical role in normal function of neurons, and alteration in their activity could contribute to disturbance in the brain function. The aim of this study was to investigate the effect of maternal diabetes on hippocampal mRNA expression and distribution pattern of glial fibrillary acidic protein (GFAP) immunoreactive glial cells in the dentate gyrus (DG) of rat neonate at postnatal day 14 (P14). Materials and Methods: Wistar female rats were randomly allocated in control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by injection of streptozotocin from 4 weeks before gestation until parturition. After delivery, the male offspring was euthanized at P14. Results: Our results showed a significant higher level of hippocampal GFAP expression and an increase in the mean number of GFAP positive cells in the DG of diabetic group offspring (P 0.05). Conclusion: The present study revealed that diabetes during pregnancy strongly increased the glial cells production in the developing rat hippocampus. PMID:27656611

  16. Intrafamilial Variability of Early-Onset Diabetes due to an INS Mutation.

    Science.gov (United States)

    Fredheim, Siri; Svensson, Jannet; Pørksen, Sven; Hansen, Lars; Hansen, Torben; Pedersen, Oluf Borbye; Mortensen, Henrik Bindesbøl; Barbetti, Fabrizio; Nielsen, Lotte Brøndum

    2011-01-01

    Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS) gene. Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule causing permanent neonatal diabetes. All three were diagnosed before 29 weeks of age, were born at term with near-normal birth weight, and were negative for GAD, ICA, IA-2, and IAA autoantibodies. The daily insulin requirement the first six months after diagnosis was INS gene.

  17. Permanent Neonatal Diabetes Caused by Creation of an Ectopic Splice Site within the INS Gene

    Science.gov (United States)

    Gastaldo, Elena; Harries, Lorna W.; Rubio-Cabezas, Oscar; Castaño, Luis

    2012-01-01

    Background The aim of this study was to characterize the genetic etiology in a patient who presented with permanent neonatal diabetes at 2 months of age. Methodology/Principal Findings Regulatory elements and coding exons 2 and 3 of the INS gene were amplified and sequenced from genomic and complementary DNA samples. A novel heterozygous INS mutation within the terminal intron of the gene was identified in the proband and her affected father. This mutation introduces an ectopic splice site leading to the insertion of 29 nucleotides from the intronic sequence into the mature mRNA, which results in a longer and abnormal transcript. Conclusions/Significance This study highlights the importance of routinely sequencing the exon-intron boundaries and the need to carry out additional studies to confirm the pathogenicity of any identified intronic genetic variants. PMID:22235272

  18. Permanent neonatal diabetes caused by creation of an ectopic splice site within the INS gene.

    Directory of Open Access Journals (Sweden)

    Intza Garin

    Full Text Available BACKGROUND: The aim of this study was to characterize the genetic etiology in a patient who presented with permanent neonatal diabetes at 2 months of age. METHODOLOGY/PRINCIPAL FINDINGS: Regulatory elements and coding exons 2 and 3 of the INS gene were amplified and sequenced from genomic and complementary DNA samples. A novel heterozygous INS mutation within the terminal intron of the gene was identified in the proband and her affected father. This mutation introduces an ectopic splice site leading to the insertion of 29 nucleotides from the intronic sequence into the mature mRNA, which results in a longer and abnormal transcript. CONCLUSIONS/SIGNIFICANCE: This study highlights the importance of routinely sequencing the exon-intron boundaries and the need to carry out additional studies to confirm the pathogenicity of any identified intronic genetic variants.

  19. Obstetric and Neonatal Outcome in PCOS with Gestational Diabetes Mellitus.

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    Fatemeh Foroozanfard

    2014-03-01

    Full Text Available There are some metabolic similarities between women with gestational diabetes mellitus (GDM and polycystic ovary syndrome (PCOS; it is still uncertain, however, to what extent coexistence GDM and PCOS affects pregnancy outcome. The present study was designed to determine the obstetric and neonatal outcome in PCOS with GDM.A case-control study was conducted involving 261 GDM women. Thirty hundred-one cases had PCOS based on Rotterdam criteria and the other thirty hundred cases (control group were women without PCOS. The subjects in each group were evaluated regarding obstetric and those women whose documentation's were complete entered the study.In present study, women with PCOS and GDM had more than twofold increased odds of preeclampsia (p = 0.003, CI = 1.56-5.01, and OR = 2.8 and PIH (p= 0.04, CI = 1.28-4.5, and OR= 2.4. Maternal PCOS and GDM were also associated with threefold increased odds of neonatal hypoglycemia (p= 0.004, CI= 1.49-6.58, and OR= 3.13.Our finding emphasized that pregnant PCOS patients should be followed carefully for the occurrence of various pregnancy and neonatal complications including hypertension and hypoglycemia. We suggested that these neonates should be given more care regarding hypoglycemia symptoms.

  20. Mitochondrial gene mutations and type 2 diabetes in Chinese families

    Institute of Scientific and Technical Information of China (English)

    LI Ming-zhen; YU De-min; YU Pei; LIU De-min; WANG Kun; TANG Xin-zhi

    2008-01-01

    Background Numerous mitochondrial DNA mutations are significantly correlated with development of diabetes. This study investigated mitochondrial gene, point mutations in patients with type 2 diabetes and their families. Methods Unrelated patients with type 2 diabetes(n=826)were randomly recruited; unrelated and nondiabetic subjects (n=637)served as controls. The clinical and biochemical data of the participants were collected. Total genome was extracted from peripheral leucocytes. Polymerase chain reaction, restriction fragment length polymorphism (PCR-RFLP)and clonig techniques were used to screen mitochondrial genes including np3316,np3394 and np3426 in the ND1 region and np3243 in the tRNALeu (UUR). Results In 39 diabetics with one or more mitochondrial gene point mutations, the prevalence(4.7%,39/826)of mtDNA mutations was higher than that(0.7%,5/637)in the controls. The identical mutation was found in 23 of 43 tested members from three pedigrees. Affected family members presented with variable clinical features ranging from normal glucose tolerance to impaired glucose tolerance (IGT)(n=2),impaired fasting glucose(IFG)(n=1)to type 2 diabetes (n=13)with 3 family members suffering from hearing loss. Conclusions Type 2 diabetes in China is associated with several mitochondrial gene mutations. Aged patients with diabetic family history had a higher prevalence of mutation and various clinical pictures. Mitochondrial gene mutation might be one of the genetic factors contributing to diabetic familial clustering.

  1. Neonatally induced diabetes: liver glycogen storage in pregnant rats

    Directory of Open Access Journals (Sweden)

    Isabela Lovizutto Iessi

    2012-04-01

    Full Text Available The aim of this sstudy was to evaluate the liver glycogen storage in pregnant rats presenting neonatal streptozotocin-induced diabetes and to establish a relation with glycemia and insulin levels. Wistar rats were divided in to two groups: 1 Mild Diabetes (STZ - received streptozotocin (glycemia from 120 to 300 mg/dL, 2 Control - received vehicle (glycemia below 120 mg/dL. At days 0, 7, 14 and 21 of the pregnancy, body weight and glycemia were evaluated. At day 21 of the pregnancy, the rats were anesthetized for blood and liver collection so as to determine insulin and liver glycogen, which showed no changes in the STZ group as compared to the controls. In the STZ group, maternal weight gain were lower as compared to those in the control group. Significantly increased glycemia was observed at days 0 and 14 of the pregnancy in the STZ group. Therefore, neonatally induced diabetes in the rats did not cause metabolic changes that impaired insulin and liver glycogen relation in these rats.

  2. Effect of Maternal Diabetes on Cerebellum Histomorphometry in Neonatal Rats

    Directory of Open Access Journals (Sweden)

    Z Khaksar

    2010-04-01

    Full Text Available Introduction: In pregnant mothers, maternal diabetes occurs when pancreas can't produce enough insulin resulting in increased blood glucose levels in the mother and subsequently in the fetus. This investigation was conducted to evaluate the effects of maternal diabetes on cerebellum of offspring of diabetic mothers (ODM, which was carried out at the veterinary faculty of Shiraz University in 2007-2008. Methods: This was an experimental study that included sixteen normal adult female rats divided in two groups. Diabetes was induced in one group by Alloxan agent. Both groups became pregnant by natural mating . At 7, 14, 21 and 28 days after birth, the cerebellum of all offsprings were collected and the weight of neonates was also measured. After producing histological slides, Olympus BX51 microscope and ‍‍‍‍‍‍‍ Olysia softwarwere used. Various histological parameters used included gray and white matters thicknesses (µ, the number of cells in gray and white matter separately per unit and the ratio of gray matter to white matter. Results: Cerebellar parameters decreased in ODM as compared to the control group. The body weight of ODM was significantly more than that of the control group (p< 0.05. Conclusions: Maternal hyperglycaemia exhibited deleterious effects on cerebellum during fetal life, which remained persistent during postneonatal period. Maternal diabetes also resulted in reduction of number of cells and thicknesses of both gray and white matter.

  3. Neonatal diabetes mellitus with heterozygous mutations in the glucokinase gene:One case report and review of ;the literature%葡萄糖激酶基因杂合突变致新生儿糖尿病一例报告并文献复习

    Institute of Scientific and Technical Information of China (English)

    赵岫; 苏喆; 潘丽丽; 王立; 张琴; 张龙江; 刘霞

    2016-01-01

    [Summary] We retrospectively described the clinical and genetic characteristics in one case of neonatal diabetes mellitus (NDM ) with heterozygous mutations in glucokinase (GCK ) gene. During the follow‐up period with diabetes diet therapy ,the self‐monitoring fasting glucose swung from 6.5 to 8.6 mmol/L ,postprandial glucose 7.1~11.3 mmol/L ,fasting insulin (FIns)2.12~10.74 mIU/ml ,C‐peptide (FC‐P)1.2~ 1.5 ng/ml and HbA1 c maintained at 6.8% . Among 14 family members ,his mother and maternal aunt had gestational diabetes and diabetes. His maternal grandpa and grandpa had diabetes.There were heterozygous mutations in GCK gene(c.1190G> T ,p.Arg397Leu) in proband and his mother , but not in his father and his twin sister. Review of the literature indicated that GCK gene heterozygous mutations can cause PNDM and MODY2. Clinical characteristics and gene sequencing are very important in the diagnosis of PNDM and MODY2 ,especially in patients with family history of diabetes.%回顾分析一例由葡萄糖激酶(GCK )基因杂合突变所致新生儿糖尿病(NDM )的临床资料和分子遗传学特征。仅予饮食干预后随访末稍血糖:FBG 6.5~8.6 mmol/L、餐后血糖(PBG )7.1~11.3 mmol/L ,FIns 2.12~10.74 mIU/ml ,FC‐P 1.2~1.5 ng/ml ,HbA1 c 6.8%。调查患儿家系14名,发现4例糖尿病患者(患儿的姨母和母亲:GDM和糖尿病;外祖父和祖父:糖尿病),患儿及其母亲存在GCK基因c.1190G> T(p.Arg397Leu)杂合突变,其父亲和双胎妹妹未见基因突变。GCK 基因杂合突变引起NDM 还是M ODY2还需进一步结合临床和基因检查鉴别,对于NDM 患儿,尤其是有糖尿病家族史者,基因检测对病因诊断尤为重要。

  4. Molecular cell biology of KATP channels: implications for neonatal diabetes.

    Science.gov (United States)

    Smith, Andrew J; Taneja, Tarvinder K; Mankouri, Jamel; Sivaprasadarao, Asipu

    2007-08-01

    ATP-sensitive potassium (KATP) channels play a key role in the regulation of insulin secretion by coupling glucose metabolism to the electrical activity of pancreatic beta-cells. To generate an electric signal of suitable magnitude, the plasma membrane of the beta-cell must contain an appropriate number of channels. An inadequate number of channels can lead to congenital hyperinsulinism, whereas an excess of channels can result in the opposite condition, neonatal diabetes. KATP channels are made up of four subunits each of Kir6.2 and the sulphonylurea receptor (SUR1), encoded by the genes KCNJ11 and ABCC8, respectively. Following synthesis, the subunits must assemble into an octameric complex to be able to exit the endoplasmic reticulum and reach the plasma membrane. While this biosynthetic pathway ensures supply of channels to the cell surface, an opposite pathway, involving clathrin-mediated endocytosis, removes channels back into the cell. The balance between these two processes, perhaps in conjunction with endocytic recycling, would dictate the channel density at the cell membrane. In this review, we discuss the molecular signals that contribute to this balance, and how an imbalance could lead to a disease state such as neonatal diabetes.

  5. Rare neonatal diabetes insipidus and associated late risks: Case report

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    Rivas-Crespo Maximiliano

    2012-05-01

    Full Text Available Abstract Background Most cases of neonatal central diabetes insipidus are caused by an injury, which often results in other handicaps in the patient. The infant’s prognosis will be determined by his or her own early age and disability as well as by the physician’s skill. However, the rarity of this condition prevents the acquisition of personal experience dealing with it. Case Presentation A neonatal hemorrhagic stroke, caused by an aortic coarctation, caused right lower limb paresis, swallowing disability, and central diabetes insipidus in a term infant. The scant oral intake, as a consequence of his disability, caused progressive undernutrition which closed a vicious circle, delaying his development and his ability to overcome the swallowing handicap. On the other hand, nasal desmopressin absorption was blocked by several common colds, resulting in brain bleeding because of severe dehydration. This even greater brain damage hampered the improvement of swallowing, closing a second harmful circle. Moreover, a devastating central myelinolysis with quadriplegia, caused by an uncontrolled intravenous infusion, consummated a pernicious sequence, possibly unreported. Conclusions The child’s overall development advanced rapidly when his nutrition was improved by gastrostomy: This was a key effect of nutrition on his highly sensitive neurodevelopment. Besides, this case shows potential risks related to intranasal desmopressin treatment in young children.

  6. Permanent neonatal diabetes in INS(C94Y) transgenic pigs.

    Science.gov (United States)

    Renner, Simone; Braun-Reichhart, Christina; Blutke, Andreas; Herbach, Nadja; Emrich, Daniela; Streckel, Elisabeth; Wünsch, Annegret; Kessler, Barbara; Kurome, Mayuko; Bähr, Andrea; Klymiuk, Nikolai; Krebs, Stefan; Puk, Oliver; Nagashima, Hiroshi; Graw, Jochen; Blum, Helmut; Wanke, Ruediger; Wolf, Eckhard

    2013-05-01

    Mutations in the insulin (INS) gene may cause permanent neonatal diabetes mellitus (PNDM). Ins2 mutant mouse models provided important insights into the disease mechanisms of PNDM but have limitations for translational research. To establish a large animal model of PNDM, we generated INS(C94Y) transgenic pigs. A line expressing high levels of INS(C94Y) mRNA (70-86% of wild-type INS transcripts) exhibited elevated blood glucose soon after birth but unaltered β-cell mass at the age of 8 days. At 4.5 months, INS(C94Y) transgenic pigs exhibited 41% reduced body weight, 72% decreased β-cell mass (-53% relative to body weight), and 60% lower fasting insulin levels compared with littermate controls. β-cells of INS(C94Y) transgenic pigs showed a marked reduction of insulin secretory granules and severe dilation of the endoplasmic reticulum. Cataract development was already visible in 8-day-old INS(C94Y) transgenic pigs and became more severe with increasing age. Diabetes-associated pathological alterations of kidney and nervous tissue were not detected during the observation period of 1 year. The stable diabetic phenotype and its rescue by insulin treatment make the INS(C94Y) transgenic pig an attractive model for insulin supplementation and islet transplantation trials, and for studying developmental consequences of maternal diabetes mellitus.

  7. Maternal and neonatal outcomes in pregnancies complicated by gestational diabetes

    DEFF Research Database (Denmark)

    Ovesen, Per Glud; Jensen, Dorte Møller; Damm, Peter

    2015-01-01

    and delivery and fetal complications were classified according to the International Classification of Diseases 10th Revision. RESULTS: The final study population consisted of 398 623 women. Of these, 9014 (2.3%) had GDM. Data were adjusted for maternal age, parity, smoking, gestational age, birth weight, BMI......OBJECTIVE: To estimate the association between gestational diabetes mellitus (GDM) and adverse pregnancy and neonatal outcomes in Denmark. METHODS: A population-based cohort study including all singleton pregnancies in Denmark from 2004 to 2010 (n = 403 092). Maternal complications during pregnancy......, gender of the fetus and calendar year. The risk of preeclampsia, caesarean section (both planned and emergency) and shoulder dystocia was increased in women with GDM. In the unadjusted analysis, the risk of thrombosis was increased by a factor 2 in the GDM patients, but in the adjusted analysis...

  8. Maternal and Neonatal Outcomes in Korean Women with Type 1 and Type 2 Diabetes

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    Hee-Sook Kim

    2015-08-01

    Full Text Available BackgroundThe purpose of this study was to evaluate maternal and neonatal outcomes in Korean women with type 1 diabetes and type 2 diabetes.MethodsWe performed a retrospective survey of 163 pregnancies in women with type 1 diabetes (n=13 and type 2 diabetes (n=150 treated from 2003 to 2010 at Cheil General Hospital & Women's Healthcare Center, Korea. We compared maternal characteristics as well as maternal and neonatal outcomes between groups.ResultsDifferences in glycosylated hemoglobin between type 1 and type 2 diabetes were not significant. Birth weight (3,501±689.6 g vs. 3,366±531.4 g and rate of major congenital malformations (7.7% vs. 5.6% were not significantly different. However, women with type 1 diabetes had higher rates of preeclampsia (38.5% vs. 8.2%, P=0.006, large for gestational age (LGA; 46.2% vs. 20.4%, P=0.004, macrosomia (38.5% vs. 13.4%, P=0.032, and admission for neonatal care (41.7% vs. 14.8%, P=0.03 than women with type 2 diabetes.ConclusionMaternal and neonatal outcomes for women with type 1 diabetes were poorer than for women with type 2 diabetes, especially preeclampsia, LGA, macrosomia and admission to the neonatal intensive care unit.

  9. The common p.R114W HNF4A mutation causes a distinct clinical subtype of monogenic diabetes

    Science.gov (United States)

    Laver, Thomas W; Colclough, Kevin; Shepherd, Maggie; Patel, Kashyap; Houghton, Jayne AL; Dusatkova, Petra; Pruhova, Stepanka; Morris, Andrew D; Palmer, Colin N; McCarthy, Mark I; Ellard, Sian; Hattersley, Andrew T; Weedon, Michael N

    2016-01-01

    HNF4A mutations cause increased birth weight, transient neonatal hypoglycaemia and maturity onset diabetes of the young (MODY). The most frequently reported HNF4A mutation is p.R114W (previously p.R127W) but functional studies have shown inconsistent results, there is lack of co-segregation in some pedigrees and an unexpectedly high frequency in public variant databases. We confirm that p.R114W is a pathogenic mutation with an odds ratio of 30.4 (95% CI: 9.79 – 125, P=2x10-21) for diabetes in our MODY cohort compared to controls. p.R114W heterozygotes do not have the increased birth weight of patients with other HNF4A mutations (3476g vs. 4147g, P=0.0004) and fewer patients responded to sulfonylurea treatment (48% vs. 73%, P=0.038). p.R114W has reduced penetrance; only 54% of heterozygotes developed diabetes by age 30 compared to 71% for other HNF4A mutations. We re-define p.R114W as a pathogenic mutation causing a distinct clinical subtype of HNF4A MODY with reduced penetrance, reduced sensitivity to sulfonylurea treatment and no effect on birth weight. This has implications for diabetes treatment, management of pregnancy and predictive testing of at-risk relatives. The increasing availability of large-scale sequence data is likely to reveal similar examples of rare, low-penetrance MODY mutations. PMID:27486234

  10. The Common p.R114W HNF4A Mutation Causes a Distinct Clinical Subtype of Monogenic Diabetes.

    Science.gov (United States)

    Laver, Thomas W; Colclough, Kevin; Shepherd, Maggie; Patel, Kashyap; Houghton, Jayne A L; Dusatkova, Petra; Pruhova, Stepanka; Morris, Andrew D; Palmer, Colin N; McCarthy, Mark I; Ellard, Sian; Hattersley, Andrew T; Weedon, Michael N

    2016-10-01

    HNF4A mutations cause increased birth weight, transient neonatal hypoglycemia, and maturity onset diabetes of the young (MODY). The most frequently reported HNF4A mutation is p.R114W (previously p.R127W), but functional studies have shown inconsistent results; there is a lack of cosegregation in some pedigrees and an unexpectedly high frequency in public variant databases. We confirm that p.R114W is a pathogenic mutation with an odds ratio of 30.4 (95% CI 9.79-125, P = 2 × 10(-21)) for diabetes in our MODY cohort compared with control subjects. p.R114W heterozygotes did not have the increased birth weight of patients with other HNF4A mutations (3,476 g vs. 4,147 g, P = 0.0004), and fewer patients responded to sulfonylurea treatment (48% vs. 73%, P = 0.038). p.R114W has reduced penetrance; only 54% of heterozygotes developed diabetes by age 30 years compared with 71% for other HNF4A mutations. We redefine p.R114W as a pathogenic mutation that causes a distinct clinical subtype of HNF4A MODY with reduced penetrance, reduced sensitivity to sulfonylurea treatment, and no effect on birth weight. This has implications for diabetes treatment, management of pregnancy, and predictive testing of at-risk relatives. The increasing availability of large-scale sequence data is likely to reveal similar examples of rare, low-penetrance MODY mutations.

  11. Genetics Home Reference: 6q24-related transient neonatal diabetes mellitus

    Science.gov (United States)

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions 6q24-related transient neonatal diabetes ...

  12. Frameshift mutations in the insulin gene leading to prolonged molecule of insulin in two families with Maturity-Onset Diabetes of the Young.

    Science.gov (United States)

    Dusatkova, Lenka; Dusatkova, Petra; Vosahlo, Jan; Vesela, Klara; Cinek, Ondrej; Lebl, Jan; Pruhova, Stepanka

    2015-04-01

    Mutations in the insulin (INS) gene rarely occur in patients with Maturity-Onset Diabetes of the Young (MODY). We aimed to describe in detail two MODY families with INS mutations. The INS gene was screened by direct sequencing. The probands and their affected relatives underwent a mixed-meal test. Mutation predictions were modeled using I-TASSER and were visualized by Swiss-PdbViewer. A novel heterozygous frameshift mutation p.Gln78fs in the INS gene was found in three generations of patients with clinically distinct diabetes. The single nucleotide deletion (c.233delA) is predicted to change and prolong amino acid sequence, resulting in aberrant proinsulin without native structures of C-peptide and A-chain. In the second family, the heterozygous mutation c.188-31G>A within the terminal intron was detected. The mother and her daughter were misdiagnosed as having type 1 diabetes since the ages of 6 and 2 years, respectively. This result is in contrast to the previously described carrier of the same mutation who was diagnosed with permanent neonatal diabetes. We identified a novel coding frameshift mutation and an intronic mutation in the INS gene leading to childhood-onset diabetes. INS mutations may result in various phenotypes, suggesting that additional mechanisms may be involved in the pathogenesis and clinical manifestation of diabetes.

  13. Genetic characteristics, clinical spectrum, and incidence of neonatal diabetes in the Emirate of AbuDhabi, United Arab Emirates.

    Science.gov (United States)

    Deeb, Asma; Habeb, Abdelhadi; Kaplan, Walid; Attia, Salima; Hadi, Suha; Osman, Amani; Al-Jubeh, Jamal; Flanagan, Sarah; DeFranco, Elisa; Ellard, Sian

    2016-03-01

    Neonatal diabetes mellitus (NDM) can be transient (TNDM) or permanent (PNDM). Data on NDM from the Gulf region are limited to few studies on PNDM.The objective of this study was to describe the genetic and clinical spectrum of NDM and estimate its incidence in AbuDhabi, capital of the United Arab Emirate (UAE). Patients were identified from the pediatric diabetes clinics and sequencing of known NDM genes was conducted in all families. Twenty-five patients were identified. Incidence during 1985-2013 was 1:29,241 Live births. Twenty-three out of twenty-five had PNDM (incidence 1:31,900) and 2/25 had TNDM (incidence 1:350,903). Eleven out of twenty-five had extra-pancreatic features and three had pancreatic aplasia. The genetic cause was detected in 21/25 (84%). Of the PNDM patients, nine had recessive EIF2AK3 mutations, six had homozygous INS mutations, two with deletion of the PTF1A enhancer, one was heterozygous for KCNJ11 mutation, one harboured a novel ABCC8 variant, and 4/21 without mutations in all known PNDM genes. One TNDM patient had a 6q24 methylation defect and another was homozygous for the INS c-331C>G mutation. This mutation also caused permanent diabetes with variable age of onset from birth to 18 years. The parents of a child with Wolcott-Rallison syndrome had a healthy girl following pre-implantation genetic diagnosis. The child with KCNJ11 mutation was successfully switched from insulin to oral sulphonylurea. The incidence of PNDM in Abu Dhabi is among the highest in the world and its spectrum is different from Europe and USA. In our cohort, genetic testing has significant implications for the clinical management.

  14. Congenital isolated adrenocorticotropin deficiency: an underestimated cause of neonatal death, explained by TPIT gene mutations.

    NARCIS (Netherlands)

    Vallette-Kasic, S.; Brue, T.; Pulichino, A.M.; Gueydan, M.; Barlier, A.; David, M.; Nicolino, M.; Malpuech, G.; Dechelotte, P.; Deal, C.; Vliet, G. van; Vroede, M.A. de; Riepe, F.G.; Partsch, C.J.; Sippell, W.G.; Berberoglu, M.; Atasay, B.; Zegher, F. de; Beckers, D.; Kyllo, J.; Donohoue, P.; Fassnacht, M.; Hahner, S.; Allolio, B.; Noordam, C.; Dunkel, L.; Hero, M.; Pigeon, B.; Weill, J.; Yigit, S.; Brauner, R.; Heinrich, J.J.; Cummings, E.; Riddell, C.; Enjalbert, A.; Drouin, J.

    2005-01-01

    Tpit is a T box transcription factor important for terminal differentiation of pituitary proopiomelanocortin-expressing cells. We demonstrated that human and mouse mutations of the TPIT gene cause a neonatal-onset form of congenital isolated ACTH deficiency (IAD). In the absence of glucocorticoid

  15. Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY

    Directory of Open Access Journals (Sweden)

    Pisinger Charlotta

    2010-03-01

    Full Text Available Abstract Background Insulin gene (INS mutations have recently been described as a common cause of permanent neonatal diabetes (PNDM and a rare cause of diabetes diagnosed in childhood or adulthood. Methods INS was sequenced in 116 maturity-onset diabetes of the young (MODYX patients (n = 48 Danish and n = 68 Czech, 83 patients with gestational diabetes mellitus (GDM, 34 type 1 diabetic patients screened negative for glutamic acid decarboxylase (GAD, and 96 glucose tolerant individuals. The control group was randomly selected from the population-based sampled Inter99 study. Results One novel heterozygous mutation c.17G>A, R6H, was identified in the pre-proinsulin gene (INS in a Danish MODYX family. The proband was diagnosed at 20 years of age with mild diabetes and treated with diet and oral hypoglycaemic agent. Two other family members who carried the INS R6H were diagnosed with diabetes when 51 years old and with GDM when 27 years old, respectively. A fourth mutation carrier had normal glucose tolerance when 20 years old. Two carriers of INS R6H were also examined twice with an oral glucose tolerance test (OGTT with 5 years interval. They both had a ~30% reduction in beta-cell function measured as insulinogenic index. In a Czech MODYX family a previously described R46Q mutation was found. The proband was diagnosed at 13 years of age and had been treated with insulin since onset of diabetes. Her mother and grandmother were diagnosed at 14 and 35 years of age, respectively, and were treated with oral hypoglycaemic agents and/or insulin. Conclusion Mutations in INS can be a rare cause of MODY and we conclude that screening for mutations in INS should be recommended in MODYX patients.

  16. Neonatal Dubin-Johnson syndrome: novel compound heterozygous mutation in the ABCC2 gene.

    Science.gov (United States)

    Okada, Hitoshi; Kusaka, Takashi; Fuke, Noriko; Kunikata, Jun; Kondo, Sonoko; Iwase, Takashi; Nan, Wang; Hirota, Takeshi; Ieiri, Ichiro; Itoh, Susumu

    2014-10-01

    Dubin-Johnson syndrome (DJS) is an autosomal recessive inherited disorder characterized by conjugated hyperbilirubinemia. Neonatal-onset DJS is rare. It is caused by dysfunction of adenosine triphosphate-binding cassette, sub-family C, member 2 (ABCC2). We found a novel compound heterozygous mutation of DJS-related gene: W709R (T2145C): a missense mutation in exon 17, and R768W (C2302T), a missense mutation in exon 18. Serum diglucuronosyl bilirubin/monoglucuronosyl bilirubin ratio was high. ABCC2 may excrete diglucuronosyl bilirubin preferentially over monoglucuronosyl bilirubin.

  17. SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain.

    Science.gov (United States)

    Liao, Y; Anttonen, A-K; Liukkonen, E; Gaily, E; Maljevic, S; Schubert, S; Bellan-Koch, A; Petrou, S; Ahonen, V E; Lerche, H; Lehesjoki, A-E

    2010-10-19

    Inherited and de novo mutations in sodium channel genes underlie a variety of channelopathies. Mutations in SCN2A, encoding the brain sodium channel Na(V)1.2, have previously been reported to be associated with benign familial neonatal infantile seizures, febrile seizures plus, and intractable epilepsy of infancy. We evaluated the clinical characteristics in a patient with a neonatal-onset complex episodic neurologic phenotype. We screened SCN2A for mutations and carried out in vitro electrophysiologic analyses to study the consequences of the identified mutation. We studied the developmental expression of Na(V)1.2 in cerebellum by immunohistochemical analysis. The patient presented with neonatal-onset seizures and variable episodes of ataxia, myoclonia, headache, and back pain after 18 months of age. The patient carries a de novo missense mutation (p.Ala263Val) in SCN2A, which leads to a pronounced gain-of-function, in particular an increased persistent Na(+) current. Immunohistochemical studies suggest a developmentally increasing expression of Na(V)1.2 in granule cell axons projecting to Purkinje neurons. These results can explain a neuronal hyperexcitability resulting in seizures and other episodic symptoms extending the spectrum of SCN2A-associated phenotypes. The developmentally increasing expression of Na(V)1.2 in cerebellum may be responsible for the later onset of episodic ataxia.

  18. Neonatal High Bone Mass With First Mutation Of The NF-κB Complex

    DEFF Research Database (Denmark)

    Frederiksen, Anja Lisbeth; Larsen, Martin Jakob; Brusgaard, Klaus

    2016-01-01

    Heritable disorders that feature high bone mass (HBM) are rare. The etiology is typically a mutation(s) within a gene that regulates the differentiation and function of osteoblasts (OBs) or osteoclasts (OCs). Nevertheless, the molecular basis is unknown for approximately one-fifth of such entities...... within the genes that encode the NF-κB complex, including the Rela/p65 subunit, have not been reported. We describe a neonate who died suddenly and unexpectedly and was found at postmortem to have HBM documented radiographically and by skeletal histopathology. Serum was not available for study...... fibroblasts elicited impaired NF-κB responses compared with healthy control fibroblasts. Five unrelated patients with unexplained HBM did not show a RELA defect. Ours is apparently the first report of a mutation within the NF-κB complex in humans. The missense change is associated with neonatal osteosclerosis...

  19. Maternal and neonatal risk factors for childhood type 1 diabetes: a matched case-control study

    Directory of Open Access Journals (Sweden)

    Harrild Kirsten

    2010-05-01

    Full Text Available Abstract Background An interaction between genetic susceptibility and environmental factors is thought to be involved in the aetiology of type 1 diabetes. The aim of this study was to investigate maternal and neonatal risk factors for type 1 diabetes in children under 15 years old in Grampian, Scotland. Methods A matched case-control study was conducted by record linkage. Cases (n = 361 were children born in Aberdeen Maternity Hospital from 1972 to 2002, inclusive, who developed type 1 diabetes, identified from the Scottish Study Group for the Care of Diabetes in the Young Register. Controls (n = 1083 were randomly selected from the Aberdeen Maternity Neonatal Databank, matched by year of birth. Exposure data were obtained from the Aberdeen Maternity Neonatal Databank. Conditional logistic regression was used to evaluate the association between various maternal and neonatal factors and the risk of type 1 diabetes. Results There was no evidence of statistically significant associations between type 1 diabetes and maternal age, maternal body mass index, previous abortions, pre-eclampsia, amniocentesis, maternal deprivation, use of syntocinon, mode of delivery, antepartum haemorrhage, baby's sex, gestational age at birth, birth order, birth weight, jaundice, phototherapy, breast feeding, admission to neonatal unit and Apgar score (P > 0.05. A significantly decreased risk of type 1 diabetes was observed in children whose mothers smoked at the booking appointment compared to those whose mothers did not, with an adjusted OR of 0.67, 95% CI (0.46, 0.99. Conclusions This case-control study found limited evidence of a reduced risk of the development of type 1 diabetes in children whose mothers smoked, compared to children whose mothers did not. No evidence was found of a significant association between other maternal and neonatal factors and childhood type 1 diabetes.

  20. Two Mutations in Surfactant Protein C Gene Associated with Neonatal Respiratory Distress

    Directory of Open Access Journals (Sweden)

    Anna Tarocco

    2015-01-01

    Full Text Available Multiple mutations of surfactant genes causing surfactant dysfunction have been described. Surfactant protein C (SP-C deficiency is associated with variable clinical manifestations ranging from neonatal respiratory distress syndrome to lethal lung disease. We present an extremely low birth weight male infant with an unusual course of respiratory distress syndrome associated with two mutations in the SFTPC gene: C43-7G>A and 12T>A. He required mechanical ventilation for 26 days and was treated with 5 subsequent doses of surfactant with temporary and short-term efficacy. He was discharged at 37 weeks of postconceptional age without any respiratory support. During the first 16 months of life he developed five respiratory infections that did not require hospitalization. Conclusion. This mild course in our patient with two mutations is peculiar because the outcome in patients with a single SFTPC mutation is usually poor.

  1. Benign familial neonatal convulsions caused by mutation in KCNQ3, exon 6: a European case.

    Science.gov (United States)

    Fister, Petja; Soltirovska-Salamon, Aneta; Debeljak, Marusa; Paro-Panjan, Darja

    2013-05-01

    Benign familial neonatal convulsions (BFNC) is a rare, clinically and genetically heterogenous epileptic disorder. Two voltage gated potassium genes, KCNQ2 and KCNQ3, have been identified as genes responsible for BFNC1 and BFNC2 respectively. While as many as 73 mutations of KCNQ2 have been described up to date, only 4 mutations in KCNQ3, 3 of them appearing in exon 5, have been identified. Mutation in exon 6 was found for the first time in a Chinese family, and here we report the same missense mutation of KCNQ3 within exon 6 in a Caucasian family, whose history and clinical picture were in accordance with BFNC. Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  2. A novel mutation of KCNQ3 gene in a Chinese family with benign familial neonatal convulsions.

    Science.gov (United States)

    Li, Haiyan; Li, Nan; Shen, Lu; Jiang, Hong; Yang, Qian; Song, Yanmin; Guo, Jifeng; Xia, Kun; Pan, Qian; Tang, Beisha

    2008-03-01

    Benign familial neonatal convulsions (BFNC, also named benign familial neonatal seizures, BFNS) is a rare autosomal dominant inherited epilepsy syndrome with clinical and genetic heterogeneity. Two voltage-gated potassium channel subunit genes, KCNQ2 and KCNQ3, have been identified to cause BFNC1 and BFNC2, respectively. To date, only three mutations of KCNQ3, all located within exon 5, have been reported. By limited linkage analysis and mutation analysis of KCNQ3 in a Chinese family with BFNC, we identified a novel missense mutation of KCNQ3, c.988C>T located within exon 6. c.988C>T led to the substitution Cys for Arg in amino acid position 330 (p.R330C) in KCNQ3 potassium channel, which possibly impaired the neuronal M-current and altered neuronal excitability. Seizures of all BFNC patients started from day 2 to 3 after birth and remitted during 1 month, and no recurrence was found. One family member who displayed fever-associated seizures for two times at age 5 years and was diagnosed as febrile seizures, however, did not carry this mutation, which suggests that febrile seizures and BFNC have different pathogenesis. To our knowledge, this is the first report of KCNQ3 mutation in Chinese family with BFNC.

  3. Diabetes Insipidus in Mice with a Mutation in Aquaporin-2.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available Congenital nephrogenic diabetes insipidus (NDI is a disease characterized by failure of the kidney to concentrate urine in response to vasopressin. Human kindreds with nephrogenic diabetes insipidus have been found to harbor mutations in the vasopressin receptor 2 (Avpr2 gene or the vasopressin-sensitive water channel aquaporin-2 (Aqp2 gene. Development of a treatment is rendered difficult due to the lack of a viable animal model. Through forward genetic screening of ethylnitrosourea-mutagenized mice, we report the identification and characterization of a mouse model of NDI, with an F204V mutation in the Aqp2 gene. Unlike previously attempted murine models of NDI, our mice survive to adulthood and more exactly recapitulate the human disorder. Previous in vitro experiments using renal cell lines suggest recessive Aqp2 mutations result in improper trafficking of the mutant water pore. Using these animals, we have directly proven this hypothesis of improper AQP2 translocation as the molecular defect in nephrogenic diabetes insipidus in the intact organism. Additionally, using a renal cell line we show that the mutated protein, AQP2-F204V, is retained in the endoplasmic reticulum and that this abnormal localization can be rescued by wild-type protein. This novel mouse model allows for further mechanistic studies as well as testing of pharmacological and gene therapies for NDI.

  4. Neonatal diabetes mellitus due to pancreatic agenesis and pervasive developmental disorder

    Directory of Open Access Journals (Sweden)

    Giannattasio Alessandro

    2009-07-01

    Full Text Available Abstract Recent studies suggested a link between type 1 diabetes mellitus and pervasive developmental disorder. Moreover, permanent neonatal diabetes mellitus due to pancreatic agenesis can be associated with neurological deficit involving cerebellar functions, but no association with pervasive developmental disorder has been described so far. Clinical and neuropsychological evaluation of a child with pancreatic agenesis, mental retardation and pervasive developmental disorder is reported.

  5. Secondary consequences of beta cell inexcitability: identification and prevention in a murine model of K(ATP)-induced neonatal diabetes mellitus.

    Science.gov (United States)

    Remedi, Maria Sara; Kurata, Harley T; Scott, Alexis; Wunderlich, F Thomas; Rother, Eva; Kleinridders, Andre; Tong, Ailing; Brüning, Jens C; Koster, Joseph C; Nichols, Colin G

    2009-02-01

    ATP-insensitive K(ATP) channel mutations cause neonatal diabetes mellitus (NDM). To explore the mechanistic etiology, we generated transgenic mice carrying an ATP-insensitive mutant K(ATP) channel subunit. Constitutive expression in pancreatic beta cells caused neonatal hyperglycemia and progression to severe diabetes and growth retardation, with loss of islet insulin content and beta cell architecture. Tamoxifen-induced expression in adult beta cells led to diabetes within 2 weeks, with similar secondary consequences. Diabetes was prevented by transplantation of normal islets under the kidney capsule. Moreover, the endogenous islets maintained normal insulin content and secretion in response to sulfonylureas, but not glucose, consistent with reduced ATP sensitivity of beta cell K(ATP) channels. In NDM, transfer to sulfonylurea therapy is less effective in older patients. This may stem from poor glycemic control or lack of insulin because glibenclamide treatment prior to tamoxifen induction prevented diabetes and secondary complications in mice but failed to halt disease progression after diabetes had developed.

  6. Secondary consequences of β-cell inexcitability: Identification and prevention in a murine model of KATP-induced Neonatal Diabetes Mellitus

    Science.gov (United States)

    Remedi, Maria Sara; Kurata, Harley T.; Scott, Alexis; Wunderlich, F. Thomas; Rother, Eva; Kleinridders, Andre; Tong, Ailing; Brüning, Jens C.; Koster, Joseph C.; Nichols, Colin G.

    2016-01-01

    ATP-insensitive KATP channel mutations cause neonatal diabetes mellitus (NDM). To explore the mechanistic etiology, we generated transgenic mice carrying an ATP-insensitive mutant KATP channel subunit. Constitutive expression in pancreatic β-cells caused neonatal hyperglycemia and progression to severe diabetes and growth retardation with loss of islet insulin content and β-cell architecture. Tamoxifen-induced expression in adult β-cells led to diabetes within 2-weeks, with similar secondary consequences. Diabetes was avoided by transplantation of normal islets under the kidney capsule, before induction. Moreover, the endogenous islets maintained normal insulin content and secretion in response to sulfonylureas, but not glucose, consistent with reduced ATP sensitivity of β-cell KATP channels. In NDM, transfer to sulfonylurea therapy is less effective in older patients. This may result from poor glycemic control or lack of insulin, since glibenclamide treatment prior to tamoxifen-induction prevented diabetes and secondary complications in mice, but failed to halt disease progression after diabetes had developed. PMID:19187772

  7. A novel CaSR mutation presenting as a severe case of neonatal familial hypocalciuric hypercalcemia

    Directory of Open Access Journals (Sweden)

    Tonyushkina Ksenia N

    2012-05-01

    Full Text Available Abstract Background Familial Hypocalciuric Hypercalcemia (FHH is a generally benign disorder caused by heterozygous inactivating mutations in the Calcium-Sensing Receptor (CaSR gene resulting in altered calcium metabolism. Objective We report a case of unusually severe neonatal FHH due to a novel CaSR gene mutation that presented with perinatal fractures and moderate hypercalcemia. Case overview A female infant was admitted at 2 weeks of age for suspected non-accidental trauma (NAT. Laboratory testing revealed hypercalcemia (3.08 mmol/L, elevated iPTH (20.4 pmol/L and low urinary calcium clearance (0.0004. Radiographs demonstrated multiple healing metaphyseal and rib fractures and bilateral femoral bowing. The femoral deformity and stage of healing were consistent with prenatal injuries rather than non-accidental trauma (NAT. Treatment was initiated with cholecalciferol, 400 IU/day, and by 6 weeks of age, iPTH levels had decreased into the high-normal range. Follow up radiographs demonstrated marked improvement of bone lesions by 3 months. A CaSR gene mutation study showed heterozygosity for a T>C nucleotide substitution at c.1664 in exon 6, resulting in amino acid change I555T in the extracellular domain consistent with a missense mutation. Her mother does not carry the mutation and the father is unknown. At 18 months of age, the child continues to have relative hyperparathyroidism and moderate hypercalcemia but is otherwise normal. Conclusion This neonate with intrauterine fractures and demineralization, moderate hypercalcemia and hyperparathyroidism was found to have a novel inactivating missense mutation of the CaSR not detected in her mother. Resolution of bone lesions and reduction of hyperparathyroidism was likely attributable to the natural evolution of the disorder in infancy as well as the mitigating effect of cholecalciferol treatment.

  8. Hyperinsulinaemic hypoglycaemia and diabetes mellitus due to dominant ABCC8/KCNJ11 mutations.

    LENUS (Irish Health Repository)

    Kapoor, R R

    2011-10-01

    Dominantly acting loss-of-function mutations in the ABCC8\\/KCNJ11 genes can cause mild medically responsive hyperinsulinaemic hypoglycaemia (HH). As controversy exists over whether these mutations predispose to diabetes in adulthood we investigated the prevalence of diabetes in families with dominantly inherited ATP-sensitive potassium (K(ATP)) channel mutations causing HH in the proband.

  9. Neonatal vitamin D status is not associated with later risk of type 1 diabetes

    DEFF Research Database (Denmark)

    Jacobsen, Ramune; Thorsen, Steffen U; Cohen, Arieh S;

    2016-01-01

    -control pairs born between 1981 and 1999 and followed up until May 2004. Both studies found no association between 25(OH)D3 levels and later risk of developing type 1 diabetes. The neonatal total 25(OH)D levels in the studies were low: 46% (case-cohort study) and 51% (case-control study) of individuals had 25...... using Danish national register data and biobank material. Weighted Cox regression and conditional logistic regression were used to calculate HRs and ORs, respectively. The concentration of 25(OH)D was assessed from neonatal dried blood spots using highly sensitive liquid chromatography-tandem mass...... spectrometry. Quintiles of 25(OH)D3 were used in the main analyses. RESULTS: The case-cohort study included 912 type 1 diabetes cases and 2866 individuals without type 1 diabetes born in Denmark between 1981 and 2002 and followed up until the end of 2012. The case-control study included 527 matched case...

  10. Neonatal vitamin D status is not associated with later risk of type 1 diabetes

    DEFF Research Database (Denmark)

    Jacobsen, Ramune; Thorsen, Steffen Ullitz; Cohen, Arieh S

    2016-01-01

    AIMS/HYPOTHESIS: The aim of this work was to assess whether neonatal levels of 25-hydroxyvitamin D (25(OH)D) are associated with risk of developing type 1 diabetes before the age of 18 years. METHODS: Two large-scale studies with different designs-a case-cohort and a case-control-were conducted......-control pairs born between 1981 and 1999 and followed up until May 2004. Both studies found no association between 25(OH)D3 levels and later risk of developing type 1 diabetes. The neonatal total 25(OH)D levels in the studies were low: 46% (case-cohort study) and 51% (case-control study) of individuals had 25......(OH)D levels levels around the time of birth were not associated with later type 1 diabetes risk. Whether higher levels of 25(OH)D3 during pregnancy, acquired by higher doses of supplementation than...

  11. V2R mutations and nephrogenic diabetes insipidus.

    Science.gov (United States)

    Bichet, Daniel G

    2009-01-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. Nephrogenic failure to concentrate urine maximally may be due to a defect in vasopressin-induced water permeability of the distal tubules and collecting ducts, to insufficient buildup of the corticopapillary interstitial osmotic gradient, or to a combination of these two factors. Thus, the broadest definition of the term NDI embraces any antidiuretic hormone-resistant urinary-concentrating defect, including medullary disease with low interstitial osmolality, renal failure, and osmotic diuresis. About 90% of patients with congenital NDI are males with X-linked recessive NDI (OMIM 304800)(1) and have mutations in the AVP receptor 2 (AVPR2) gene that codes for the vasopressin V(2) receptor; the gene is located in chromosome region Xq28. In about 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance (OMIM 222000 and 125800)(1). Mutations have been identified in the aquaporin-2 gene (AQP2, OMIM 107777)(1), which is located in chromosome region 12q13 and codes for the vasopressin-sensitive water channel. NDI is clinically distinguishable from neurohypophyseal diabetes insipidus (OMIM 125700(1); also referred to as central or neurogenic diabetes insipidus) by a lack of response to exogenous AVP and by plasma levels of AVP that rise normally with increase in plasma osmolality. Hereditary neurohypophyseal diabetes insipidus is secondary to mutations in the gene encoding AVP (OMIM 192340)(1). Neurohypophyseal diabetes insipidus is also a component of autosomal recessive Wolfram syndrome 1 or DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) (OMIM

  12. Relationship between mutations of mitochondrial DNA ND1 gene and type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    于珮; 于德民; 刘德敏; 王琨; 汤新之

    2004-01-01

    Background Recent studies have indicated that many mutations in mitochondrial (mt)DNA NDI gene region are related to diabetes mellitus. In this study we explored the relationship between various mtDNA ND1 gene mutations and type 2 diabetes mellitus (DM) among Chinese. Methods Using PCR restriction fragment length polymorphism (PCR-RFLP) analysis and gene sequencing, 4 spots of mtDNA (nt3243, nt3316, nt3394, nt3426) were screened in 478 diabetics and 430 non-diabetic subjects.Results In diabetic group, there were 13 carriers (2.72%)of 3316 G→A mutation,12 (2.51%) of 3394 T→C mutation and 2 (0.42%) of 3426A→G mutation. In controls, only 3394 T→C mutation was observed in 2 subjects (0.47%). There was significant difference in the frequency of 3316 and 3394 mutation between two groups (P<0.05, respectively). More subjects with mitochondrial DNA ND1 gene mutations had DM family history and greater tendency of maternal inheritance when compared to those patients without mutation in diabetic group(P<0.01). A 3426 mutation diabetic pedigree was studied, and we found 12 maternal members in the family had the same mutation. Conclusion mtDNA ND1 gene mutations at nt3316 (G→A), nt3394 (T→C) and 3426 (A→G) might contribute to the pathogenesis of DM with other genetic factors and environment factors.

  13. A Mutation Identified in Neonatal Microcephaly Destabilizes Zika Virus NS1 Assembly in Vitro

    Science.gov (United States)

    Wang, Deping; Chen, Cheng; Liu, Shengnan; Zhou, Han; Yang, Kailin; Zhao, Qi; Ji, Xiaoyun; Chen, Chen; Xie, Wei; Wang, Zefang; Mi, Li-Zhi; Yang, Haitao

    2017-01-01

    An unprecedented epidemic of Zika virus (ZIKV) infection had spread to South and Central America. ZIKV infection was recently confirmed by CDC (the Centers for Disease Control and Prevention) to cause neonatal microcephaly, which posed a significant public health emergency of international concern. No specific vaccines or drugs are currently available to fight ZIKV infection. ZIKV nonstructural protein 1 (NS1) plays an essential role in viral replication and immune evasion. We determined the crystal structure of ZIKV NS1172–352, which forms a head-to-head, symmetric dimer with a unique 14-stranded β-ladder conserved among flaviviruses. The assembly of the β-ladder dimer is concentration dependent. Strikingly, one pathogenic mutation T233A (NCBI accession no. KU527068), found in the brain tissue of infected fetus with neonatal microcephaly, is located at the dimer interface. Thr233, a unique residue found in ZIKV but not in other flaviviruses, organizes a central hydrogen bonding network at NS1 dimer interface. Mutation of Thr233 to Ala disrupts this elaborated interaction network, and destabilizes the NS1 dimeric assembly in vitro. In addition, our structural comparison of epitopes for protective antibody 22NS1, targeting West Nile Virus NS1, could potentially be valuable in understanding its anti-virus specificities and in the development of antibodies against ZIKV. PMID:28198446

  14. Copeptin and MR-proADM in umbilical cord plasma reflect perinatal stress in neonates born to mothers with diabetes and MR-proANP reflects maternal diabetes

    DEFF Research Database (Denmark)

    Smith, Julie; Halse, Karen G; Damm, Peter

    2013-01-01

    To examine concentrations of three cardiovascular propeptides in umbilical cord plasma of neonates born to mothers with Type 1, Type 2 and gestational diabetes. Measurement of cardiovascular markers in umbilical cord plasma may potentially help identify neonates at risk of postnatal complications...

  15. Maternal and neonatal outcomes of gestational diabetes: A retrospective cohort study from Southern India

    Science.gov (United States)

    Sreelakshmi, P. R.; Nair, Sanjeev; Soman, Biju; Alex, Rani; Vijayakumar, K.; Kutty, V. Raman

    2015-01-01

    Background: The prevalence of gestational diabetes is on the rise. Understanding the various outcomes of it is necessary to face this challenge. Objectives: To study the frequency of occurrence of various maternal and fetal outcomes among gestational diabetes patients. Methods: This is a retrospective cohort study conducted in rural Kerala, a southern state of India. The study participants were followed up for a period of 4 years, from 2007 to 2011. The participants included 60 women with gestational diabetes and 120 women without gestational diabetes. Gestational diabetes was the major exposure variable. The frequencies of various outcomes were computed. Multivariable logistic regression was done to compute the risk for various outcomes in gestational diabetes. Results: The major outcomes included termination of pregnancy by caesarean section, long-term progression to type 2 diabetes, in-born nursery (IBN) admissions and increased neonatal birth weight. The maximum adjusted RR [13.2 (1.5-116.03)] was for the development of type 2 DM later. Conclusion: Gestational diabetes can result in significant feto-maternal outcomes; so better facilities are needed to manage gestational diabetes. PMID:26288780

  16. Bilateral cataracts in a 6-yr-old with new onset diabetes: a novel presentation of a known INS gene mutation.

    Science.gov (United States)

    Wasserman, Halley; Hufnagel, Robert B; Miraldi Utz, Virginia; Zhang, Kejian; Valencia, C Alexander; Leslie, Nancy D; Crimmins, Nancy A

    2016-11-01

    The prevalence of diabetes-related cataracts during childhood is less than 1%. When cataracts occur, it is often in adolescent females with prolonged symptoms and significant hyperglycemia. Cataracts are not a classic feature of monogenic diabetes. We report a case of a 6-yr-old, previously healthy Caucasian male, who presented with bilateral acquired cataracts and was subsequently diagnosed with new onset diabetes. Additional symptoms at presentation included a several year history of polyuria and polydipsia, mild hepatomegaly, and short stature. Pertinent negatives include acanthosis nigricans, lipoatrophy, deafness, muscle weakness, or neuropathy. HbA1c was significantly elevated at diagnosis (>14%, 129.5 mmol/mol) without evidence of ketosis. Autoantibody testing was negative. Features of Mauriac syndrome (short stature, hepatomegaly) as well as acquired cataracts indicated long-standing hyperglycemia with sufficient insulin production to prevent ketone production and development of diabetic ketoacidosis. Whole exome sequencing was conducted and a de novo heterozygous mutation in the INS gene (c.94G>A; p.Gly32Ser) was identified. INS gene mutations are common causes of permanent neonatal diabetes but rare causes of antibody-negative diabetes in children. Importantly, INS gene mutations have not been previously associated with acquired cataracts. Knowledge of a monogenic cause of diabetes allows clinicians to tailor counseling and screening of diabetes-related comorbidities. In summary, this case highlights the need to consider testing for monogenic diabetes, specifically INS gene mutations, in pediatric patients with antibody-negative diabetes, especially if complications of prolonged hyperglycemia are present at diagnosis.

  17. Novel α-spectrin mutation in trans with α-spectrin causing severe neonatal jaundice from hereditary spherocytosis.

    Science.gov (United States)

    Nussenzveig, Roberto H; Christensen, Robert D; Prchal, Josef T; Yaish, Hassan M; Agarwal, Archana M

    2014-01-01

    We evaluated a neonate with severe jaundice but a negative family history. Spherocytes were present and suspected hereditary spherocytosis was confirmed by osmotic fragility and eosin-5-maleimide erythrocyte staining. We found he was a compound heterozygote for two pathogenic mutations in the gene encoding α-spectrin: a previously reported α(LEPRA) inherited from his asymptomatic mother, and a novel α-spectrin mutation in intron 45 +1 disrupting the consensus splice site, from his asymptomatic father.

  18. 6q24 transient neonatal diabetes – how to manage while waiting for genetic results

    Directory of Open Access Journals (Sweden)

    Corina Ramona Nicolescu

    2016-11-01

    Full Text Available Diabetes, rare in the neonatal period, should be evoked in every newborn presenting with unexplained intrauterine and early postnatal growth retardation.This case report illustrates the clinical course and therapeutic approach of a newborn diagnosed with transient diabetes. The baby was born at 37 weeks of gestation with a severe intrauterine growth restriction. Except a mild macroglossia and signs of growth restriction, physical examination was normal. On the 5th day of life hyperglycemia (180 mg/dl was noted and the next day the diagnosis of diabetes was confirmed (high blood sugar, glucosuria, undetectable levels of insulin and C-peptide. Insulin infusion, initially intravenously and then subcutaneously was started, tailored to assure the growth catch-up and normalize the blood sugar levels. At the age of 4 weeks, the baby returned at home under pump.At 8 weeks, the clinical impression of evolution to a transient diabetes (decreasing needs of insulin with very satisfactory weight gain was genetically confirmed (paternal uniparental disomy of chromosome 6.There is no screening for neonatal diabetes, but the clinical suspicion avoids the metabolic decompensation and allows early initiation of insulin therapy. The genetic approach (for disease itself and its associated features relies on timely clinical updates.

  19. 6q24 Transient Neonatal Diabetes – How to Manage while Waiting for Genetic Results

    Science.gov (United States)

    Fudvoye, Julie; Farhat, Khaldoun; De Halleux, Virginie; Nicolescu, Corina Ramona

    2016-01-01

    Diabetes, rare in the neonatal period, should be evoked in every newborn presenting with unexplained intrauterine and early postnatal growth retardation. This case report illustrates the clinical course and therapeutic approach of a newborn diagnosed with transient diabetes. The baby was born at 37 weeks of gestation with a severe intrauterine growth restriction. Except a mild macroglossia and signs of growth restriction, physical examination was normal. On the fifth day of life, hyperglycemia (180 mg/dl) was noted, and the next day, the diagnosis of diabetes was confirmed (high blood sugar, glucosuria, undetectable levels of insulin and C-peptide). Insulin infusion, initially intravenously and then subcutaneously, was started, tailored to assure the growth catch-up and normalize the blood sugar levels. At the age of 4 weeks, the baby returned at home under pump. At 8 weeks, the clinical impression of evolution to a transient diabetes (decreasing needs of insulin with very satisfactory weight gain) was genetically confirmed (paternal uniparental disomy of chromosome 6). There is no screening for neonatal diabetes, but the clinical suspicion avoids the metabolic decompensation and allows early initiation of insulin therapy. The genetic approach (for disease itself and its associated features) relies on timely clinical updates. PMID:27909691

  20. Effect of Costus igneus: The insulin plant, on prediabetes and diabetes in neonatal streptozotocin rats

    Directory of Open Access Journals (Sweden)

    Murthy EGK Talasila

    2014-12-01

    Full Text Available Introduction: Pre-diabetes is a condition that persists for a considerable duration before progressing into type 2 diabetes mellitus (T2DM. Development of resistance to insulin is the underlying cause of pre-diabetes, preventive measures such as diagnosis, treatment and exercise will preclude its development into T2DM. The present study aims at studying the effect of pre-treatment and post-treatment with isolated fraction of Costus igneus on pre-diabetes and diabetes in neonatal streptozotocin (STZ induced T2DM.Methods: Neonatal rats were treated with STZ and differentiated for pre-treatment and post-treatment. Rats of pre-treated group were treated with isolated fraction of Costus igneus (CIF from 4th week after STZ administration and after 12th week in non-treated rats of post-treatment group. The antihyperglycemic was studied on 7th and 12th week after STZ treatment using oral glucose tolerance test and the hypoglycemic effect was studied on day 1, 7, 14 and 21 of treatment after 12th week of STZ treatment in both pre and post treated groups.Results: Oral glucose tolerance test on 7th and 12th week had shown a protective effect against increase in blood glucose levels in pre-treated groups whereas, no such significant decrease was observed in non-treated groups. In the effect on hypoglycemia, a reduction in blood glucose levels was observed on treatment with CIF in both pre and post treated rats on 14th and 21st day.Conclusions: Treatment with CIF in pre-diabetic stage could reduce the chances of progression into T2DM and is also beneficial in diabetic rats, which could be due to increase in the peripheral utilization of glucose and the insulin mimetic effect of Costus igneus.

  1. Neonatally Induced Mild Diabetes in Rats and Its Effect on Maternal, Placental, and Fetal Parameters

    Directory of Open Access Journals (Sweden)

    Yuri Karen Sinzato

    2012-01-01

    Full Text Available The aim of this study was to assess placental changes and reproductive outcomes in neonatally induced mild diabetic dams and fetal development in their offspring. At birth, female rats were assigned either to control or diabetic group (100 mg of streptozotocin/Kg, subcutaneously. At adulthood, the female rats were mated. During pregnancy, the blood glucose levels and glucose and insulin tolerance tests were performed. At term, maternal reproductive outcomes, fetal and placental weight, and placental morphology were analyzed. Diabetic rats had smaller number of living fetuses, implantations and corpora lutea, and increased rate of embryonic loss. Placenta showed morphometric alterations in decidua area. Our results showed that mild diabetes was sufficient to trigger alterations in maternal organism leading to impaired decidua development contributing to failure in embryonic implantation and early embryonic losses. Regardless placental decidua alteration, the labyrinth, which is responsible for the maternal-fetal exchanges, showed no morphometric changes contributing to an appropriate fetal development, which was able to maintain normal fetal weight at term in mild diabetic rats. Thus, this experimental model of diabetes induction at the day of birth was more effective to reproduce the reproductive alterations of diabetic women.

  2. A novel mutation leading to a premature stop codon in inlA of Listeria monocytogenes isolated from neonatal listeriosis.

    Science.gov (United States)

    Gelbíčová, Tereza; Koláčková, Ivana; Pantůček, Roman; Karpíšková, Renáta

    2015-04-01

    The study objective was to investigate whether the strain of L. monocytogenes serotype 1/2c isolated from neonatal listeriosis carries a premature stop codon (PMSC) mutation in the inlA gene. The strain was characterized by serotyping, macrorestriction analysis after digestion with the restriction enzyme AscI, and sequencing of the inlA gene. The tested strain of serotype 1/2c and pulsotype 1 possesses a new type of point mutation leading to a PMSC in the inlA gene and production of truncated internalin A. The case of early onset form of neonatal listeriosis caused by serotype 1/2c with a PMSC mutation in the inlA gene confirmed the transplacental transmission potential of this strain.

  3. Characterization of two novel missense mutations in the AQP2 gene causing nephrogenic diabetes insipidus.

    NARCIS (Netherlands)

    Iolascon, A.; Aglio, V.; Tamma, G.; D'Apolito, M.; Addabbo, F.; Procino, G.; Simonetti, M.C.; Montini, G.; Gesualdo, L.; Debler, E.W.; Svelto, M.; Valenti, G.

    2007-01-01

    Here, we report the aquaporin 2 (AQP2) mutational analysis of a patient with nephrogenic diabetes insipidus heterozygote due to two novel missense mutations. Direct sequencing of DNA in the male patient revealed that he was compound heterozygote for two mutations in the AQP2 gene: a thymine-to-adeni

  4. Early feeding and neonatal hypoglycemia in infants of diabetic mothers

    Directory of Open Access Journals (Sweden)

    Leandro Cordero

    2013-12-01

    Full Text Available Objectives: To examine the effects of early formula feeding or breast-feeding on hypoglycemia in infants born to 303 A1-A2 and 88 Class B-RF diabetics. Methods: Infants with hypoglycemia (blood glucose < 40 mg/dL were breast-fed or formula-fed, and those with recurrences were given intravenous dextrose. Results: Of 293 infants admitted to the well-baby nursery, 87 (30% had hypoglycemia, corrected by early feeding in 75 (86%, while 12 (14% required intravenous dextrose. In all, 98 infants were admitted to the newborn intensive care unit for respiratory distress (40%, prematurity (33% or prevention of hypoglycemia (27%. Although all newborn intensive care unit patients received intravenous dextrose, 22 (22% had hypoglycemia. Of 109 hypoglycemia episodes, 89 (82% were single low occurrences. At discharge, 56% of well-baby nursery and 43% of newborn intensive care unit infants initiated breast-feeding. Conclusions: Hypoglycemia among infants of diabetic mothers can be corrected by early breast-feeding or formula feeding.

  5. Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy.

    Science.gov (United States)

    Habarou, Florence; Hamel, Yamina; Haack, Tobias B; Feichtinger, René G; Lebigot, Elise; Marquardt, Iris; Busiah, Kanetee; Laroche, Cécile; Madrange, Marine; Grisel, Coraline; Pontoizeau, Clément; Eisermann, Monika; Boutron, Audrey; Chrétien, Dominique; Chadefaux-Vekemans, Bernadette; Barouki, Robert; Bole-Feysot, Christine; Nitschke, Patrick; Goudin, Nicolas; Boddaert, Nathalie; Nemazanyy, Ivan; Delahodde, Agnès; Kölker, Stefan; Rodenburg, Richard J; Korenke, G Christoph; Meitinger, Thomas; Strom, Tim M; Prokisch, Holger; Rotig, Agnes; Ottolenghi, Chris; Mayr, Johannes A; de Lonlay, Pascale

    2017-08-03

    Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2-oxoacid dehydrogenases functioning in energy metabolism (α-oxoglutarate dehydrogenase [α-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase). Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency spares GCS deficiency and has been associated with a biochemical signature of combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like encephalopathy. We report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy. Brain MRI showed major cortical atrophy with white matter abnormalities and cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts showed reduced oxygen consumption rates, PDHc, α-KGDHc activities, leucine catabolic flux, and decreased protein lipoylation. A normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not improve clinical condition nor activities of PDHc, α-KGDHc, or leucine metabolism in fibroblasts and was ineffective in yeast deleted for the orthologous LIP2. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  6. Lipodystrophy, Diabetes and Normal Serum Insulin in PPARγ-Deficient Neonatal Mice

    Science.gov (United States)

    O’Donnell, Peter E.; Ye, Xiu Zhen; DeChellis, Melissa A.; Davis, Vannessa M.; Duan, Sheng Zhong; Mortensen, Richard M.; Milstone, David S.

    2016-01-01

    Peroxisome proliferator activated receptor gamma (PPARγ) is a pleiotropic ligand activated transcription factor that acts in several tissues to regulate adipocyte differentiation, lipid metabolism, insulin sensitivity and glucose homeostasis. PPARγ also regulates cardiomyocyte homeostasis and by virtue of its obligate role in placental development is required for embryonic survival. To determine the postnatal functions of PPARγ in vivo we studied globally deficient neonatal mice produced by epiblast-restricted elimination of PPARγ. PPARγ-rescued placentas support development of PPARγ-deficient embryos that are viable and born in near normal numbers. However, PPARγ-deficient neonatal mice show severe lipodystrophy, lipemia, hepatic steatosis with focal hepatitis, relative insulin deficiency and diabetes beginning soon after birth and culminating in failure to thrive and neonatal lethality between 4 and 10 days of age. These abnormalities are not observed with selective PPARγ2 deficiency or with deficiency restricted to hepatocytes, skeletal muscle, adipocytes, cardiomyocytes, endothelium or pancreatic beta cells. These observations suggest important but previously unappreciated functions for PPARγ1 in the neonatal period either alone or in combination with PPARγ2 in lipid metabolism, glucose homeostasis and insulin sensitivity. PMID:27505464

  7. Neonatal pyruvate dehydrogenase deficiency due to a R302H mutation in the PDHA1 gene: MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Soares-Fernandes, Joao P.; Ribeiro, Manuel; Magalhaes, Zita; Rocha, Jaime F. [Hospital de S. Marcos, Department of Neuroradiology, Braga (Portugal); Teixeira-Gomes, Roseli [Hospital Pedro Hispano, Division of Neuropediatrics, Matosinhos (Portugal); Cruz, Romeu [Hospital Geral de Sto. Antonio, Department of Neuroradiology, Porto (Portugal); Leijser, Lara M. [Leiden University Medical Center, Department of Paediatrics, Division of Neonatology, Leiden (Netherlands)

    2008-05-15

    Pyruvate dehydrogenase (PDH) deficiency is one of the most common causes of congenital lactic acidosis. Correlations between the genetic defect and neuroimaging findings are lacking. We present conventional and diffusion-weighted MRI findings in a 7-day-old male neonate with PDH deficiency due to a mosaicism for the R302H mutation in the PDHA1 gene. Corpus callosum dysgenesis, widespread increased diffusion in the white matter, and bilateral subependymal cysts were the main features. Although confirmation of PDH deficiency depends on specialized biochemical analyses, neonatal MRI plays a role in evaluating the pattern and extent of brain damage, and potentially in early diagnosis and clinical decision making. (orig.)

  8. Neonatal progeroid variant of Marfan syndrome with congenital lipodystrophy results from mutations at the 3' end of FBN1 gene.

    Science.gov (United States)

    Jacquinet, Adeline; Verloes, Alain; Callewaert, Bert; Coremans, Christine; Coucke, Paul; de Paepe, Anne; Kornak, Uwe; Lebrun, Frederic; Lombet, Jacques; Piérard, Gérald E; Robinson, Peter N; Symoens, Sofie; Van Maldergem, Lionel; Debray, François-Guillaume

    2014-04-01

    We report a 16-year-old girl with neonatal progeroid features and congenital lipodystrophy who was considered at birth as a possible variant of Wiedemann-Rautenstrauch syndrome. The emergence of additional clinical signs (marfanoid habitus, severe myopia and dilatation of the aortic bulb) lead to consider the diagnosis of the progeroid variant of Marfan syndrome. A de novo donor splice-site mutation (c.8226+1G>A) was identified in FBN1. We show that this mutation leads to exon 64 skipping and to the production of a stable mRNA that should allow synthesis of a truncated profibrillin-1, in which the C-terminal furin cleavage site is altered. FBN1 mutations associated with a similar phenotype have only been reported in four other patients. We confirm the correlation between marfanoid phenotype with congenital lipodystrophy and neonatal progeroid features (marfanoid-progeroid-lipodystrophy syndrome) and frameshift mutations at the 3' end of FBN1. This syndrome should be considered in differential diagnosis of neonatal progeroid syndromes.

  9. Gene-specific function prediction for non-synonymous mutations in monogenic diabetes genes.

    Directory of Open Access Journals (Sweden)

    Quan Li

    Full Text Available The rapid progress of genomic technologies has been providing new opportunities to address the need of maturity-onset diabetes of the young (MODY molecular diagnosis. However, whether a new mutation causes MODY can be questionable. A number of in silico methods have been developed to predict functional effects of rare human mutations. The purpose of this study is to compare the performance of different bioinformatics methods in the functional prediction of nonsynonymous mutations in each MODY gene, and provides reference matrices to assist the molecular diagnosis of MODY. Our study showed that the prediction scores by different methods of the diabetes mutations were highly correlated, but were more complimentary than replacement to each other. The available in silico methods for the prediction of diabetes mutations had varied performances across different genes. Applying gene-specific thresholds defined by this study may be able to increase the performance of in silico prediction of disease-causing mutations.

  10. Neonatal diabetes mellitus and congenital diaphragmatic hernia: coincidence or concurrent etiology?

    Directory of Open Access Journals (Sweden)

    Topiol Emmanuelle S

    2012-07-01

    Full Text Available Abstract Neonatal diabetes mellitus (NDM is a rare metabolic disorder, affecting approximately 1 in 500,000 live births. The management of NDM is challenging, as the benefits of controlling hyperglycemia must be balanced with the risks of iatrogenic hypoglycemia. NDM occurs in both permanent and transient forms, which have been genetically and phenotypically well characterized. Herein, we present the previously unreported combination of transient NDM (TNDM and congenital diaphragmatic hernia (CDH. In addition to reviewing the management and genetics of NDM we discuss the potential for overlapping genetic or embryologic abnormalities to explain the concurrence of CDH and NDM.

  11. Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia.

    Science.gov (United States)

    Schwarz, N; Hahn, A; Bast, T; Müller, S; Löffler, H; Maljevic, S; Gaily, E; Prehl, I; Biskup, S; Joensuu, T; Lehesjoki, A-E; Neubauer, B A; Lerche, H; Hedrich, U B S

    2016-02-01

    Mutations in SCN2A cause epilepsy syndromes of variable severity including neonatal-infantile seizures. In one case, we previously described additional childhood-onset episodic ataxia. Here, we corroborate and detail the latter phenotype in three further cases. We describe the clinical characteristics, identify the causative SCN2A mutations and determine their functional consequences using whole-cell patch-clamping in mammalian cells. In total, four probands presented with neonatal-onset seizures remitting after five to 13 months. In early childhood, they started to experience repeated episodes of ataxia, accompanied in part by headache or back pain lasting minutes to several hours. In two of the new cases, we detected the novel mutation p.Arg1882Gly. While this mutation occurred de novo in both patients, one of them carries an additional known variant on the same SCN2A allele, inherited from the unaffected father (p.Gly1522Ala). Whereas p.Arg1882Gly alone shifted the activation curve by -4 mV, the combination of both variants did not affect activation, but caused a depolarizing shift of voltage-dependent inactivation, and a significant increase in Na(+) current density and protein production. p.Gly1522Ala alone did not change channel gating. The third new proband carries the same de novo SCN2A gain-of-function mutation as our first published case (p.Ala263Val). Our findings broaden the clinical spectrum observed with SCN2A gain-of-function mutations, showing that fairly different biophysical mechanisms can cause a convergent clinical phenotype of neonatal seizures and later onset episodic ataxia.

  12. Defects in beta cell Ca2+ signalling, glucose metabolism and insulin secretion in a murine model of KATP channel-induced neonatal diabetes mellitus

    Science.gov (United States)

    Benninger, R. K. P.; Remedi, M. S.; Head, W. S.; Ustione, A.; Piston, D. W.; Nichols, C. G.

    2011-01-01

    Aims/hypothesis Mutations that render ATP-sensitive potassium (KATP) channels insensitive to ATP inhibition cause neonatal diabetes mellitus. In mice, these mutations cause insulin secretion to be lost initially and, as the disease progresses, beta cell mass and insulin content also disappear. We investigated whether defects in calcium signalling alone are sufficient to explain short-term and long-term islet dysfunction. Methods We examined the metabolic, electrical and insulin secretion response in islets from mice that become diabetic after induction of ATP-insensitive Kir6.2 expression. To separate direct effects of KATP overactivity on beta cell function from indirect effects of prolonged hyperglycaemia, normal glycaemia was maintained by protective exogenous islet transplantation. Results In endogenous islets from protected animals, glucose-dependent elevations of intracellular free-calcium activity ([Ca2+]i) were severely blunted. Insulin content of these islets was normal, and sulfonylureas and KCl stimulated increased [Ca2+]i. In the absence of transplant protection, [Ca2+]i responses were similar, but glucose metabolism and redox state were dramatically altered; sulfonylurea- and KCl-stimulated insulin secretion was also lost, because of systemic effects induced by long-term hyperglycaemia and/or hypoinsulinaemia. In both cases, [Ca2+]i dynamics were synchronous across the islet. After reduction of gap-junction coupling, glucose-dependent [Ca2+]i and insulin secretion was partially restored, indicating that excitability of weakly expressing cells is suppressed by cells expressing mutants, via gap-junctions. Conclusions/interpretation The primary defect in KATP-induced neonatal diabetes mellitus is failure of glucose metabolism to elevate [Ca2+]i, which suppresses insulin secretion and mildly alters islet glucose metabolism. Loss of insulin content and mitochondrial dysfunction are secondary to the long-term hyperglycaemia and/or hypoinsulinaemia that

  13. "COMPARISON OF MATERNAL AND FETAL/NEONATAL COMPLICATIONS IN GESTATIONAL AND PRE-GESTATIONAL DIABETES MELLITUS "

    Directory of Open Access Journals (Sweden)

    F. Akhlaghi A. B. Hamedi

    2005-07-01

    Full Text Available Presence of maternal diabetes mellitus (DM during pregnancy has important consequences for both mother and child. To determine maternal and fetal/neonatal complications of gestational DM and compare them with pre-gestational DM, a prospective study was performed in 100 diabetic women delivered in our hospital from January 2001 to April 2002. Pregnancy outcome in 27 women with gestational DM and 73 women with pre-gestational DM and their offspring were studied and analyzed. The mean age of women was 28 years, women with gestational DM being slightly older than women with pre-gestational DM. Mothers with gestational DM were at increased risk of presenting with pre-eclampsia and preterm labor compared to pre-gestational DM. Frequency of Cesarean section was higher in mothers with pre-gestational DM. Frequencies of abortion and hypoglycemic episodes were similar in gestational DM and pre-gestational DM. Infants born to mothers with pre-gestational DM were at increased risk of suffering from respiratory distress syndrome and congenital malformations but rates of unexplained intrauterine fetal death and large for gestational age were higher in infant of mothers with gestational DM. Gestational and pre-gestational DM are associated with increased risk of maternal and neonatal morbidity. Pregnant women with gestational and pre-gestational DM and their offsprings should be monitored and managed carefully.

  14. Vitamin D Deficiency Increases the Risk of Adverse Neonatal Outcomes in Gestational Diabetes

    Science.gov (United States)

    Weinert, Letícia Schwerz; Reichelt, Angela Jacob; Schmitt, Leonardo Rauber; Boff, Roberta; Oppermann, Maria Lucia Rocha; Camargo, Joiza Lins; Silveiro, Sandra Pinho

    2016-01-01

    Background Gestational diabetes mellitus (GDM) and vitamin D deficiency have been associated with increased risk of adverse perinatal outcomes but the consequences of both conditions simultaneously present in pregnancy have not yet been evaluated. Our objective was to study the influence of vitamin D deficiency in neonatal outcomes of pregnancies with GDM. Methods 184 pregnant women with GDM referred to specialized prenatal monitoring were included in this cohort and had blood sampled for 25-hydroxyvitamin D measurement. Vitamin D was measured by chemiluminescence and deficiency was defined as < 20 ng/mL. Participants were followed until puerperium and adverse neonatal outcomes were evaluated. Results Newborns of women with vitamin D deficiency had higher incidences of hospitalization in intensive care units (ICU) (32 vs 19%, P = 0.048), of hypoglycemia (any, 17.3 vs 7.1%, P = 0.039requiring ICU, 15.3 vs 3.6%, P = 0.008), and were more frequently small for gestational age (SGA) (17.3 vs 5.9%, P = 0.017). After adjustment, relative risk (RR) for hypoglycemia requiring ICU was 3.63 (95%CI 1.09–12.11) and for SGA was 4.32 (95%CI 1.75–10.66). The incidence of prematurity, jaundice and shoulder dystocia was no statistically different between groups. Conclusions In this cohort of pregnant women with GDM, vitamin D deficiency was associated with a major increase in the incidence of adverse neonatal outcomes such as SGA newborns and neonatal hypoglycemia. PMID:27764194

  15. Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    Anke; Hoffmann; Dietmar; Spengler

    2015-01-01

    Transient neonatal diabetes mellitus 1(TNDM1) is a rare genetic disorder representing with severe neonatal hyperglycaemia followed by remission within one and a half year and adolescent relapse with type 2 diabetes in half of the patients. Genetic defects in TNDM1 comprise uniparental isodisomy of chromosome 6, duplication of the minimal TNDM1 locus at 6q24, or relaxation of genomically imprinted ZAC1 /HYMAI. Whereas the function of HYMAI, a non-coding m RNA, is still unidentified, biochemical and molecular studies show that zinc finger protein 1 regulating apoptosis and cell cycle arrest(ZAC1) behaves as a factor with versatile transcriptional functions dependent on binding to specific GC-rich DNA motives and interconnected regulation of recruited coactivator activities. Genome-wide expression profiling enabled the isolation of a number of Zac1 target genes known to regulate different aspects of β-cell function and peripheral insulin sensitivity. Among these, upregulation of Pparγ and Tcf4 impairs insulinsecretion and β-cell proliferation. Similarly, Zac1-mediated upregulation of Socs3 may attenuate β-cell proliferation and survival by inhibition of growth factor signalling. Additionally, Zac1 directly represses Pac1 and Rasgrf1 with roles in insulin secretion and β-cell proliferation. Collectively, concerted dysregulation of these target genes could contribute to the onset and course of TNDM1. Interestingly, Zac1 overexpression in β-cells spares the effects of stimulatory G-protein signaling on insulin secretion and raises the prospect for tailored treatments in relapsed TNDM1 patients. Overall, these results suggest that progress on the molecular and cellular foundations of monogenetic forms of diabetes can advance personalized therapy in addition to deepening the understanding of insulin and glucose metabolism in general.

  16. Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism.

    Science.gov (United States)

    Hoffmann, Anke; Spengler, Dietmar

    2015-08-26

    Transient neonatal diabetes mellitus 1 (TNDM1) is a rare genetic disorder representing with severe neonatal hyperglycaemia followed by remission within one and a half year and adolescent relapse with type 2 diabetes in half of the patients. Genetic defects in TNDM1 comprise uniparental isodisomy of chromosome 6, duplication of the minimal TNDM1 locus at 6q24, or relaxation of genomically imprinted ZAC1/HYMAI. Whereas the function of HYMAI, a non-coding mRNA, is still unidentified, biochemical and molecular studies show that zinc finger protein 1 regulating apoptosis and cell cycle arrest (ZAC1) behaves as a factor with versatile transcriptional functions dependent on binding to specific GC-rich DNA motives and interconnected regulation of recruited coactivator activities. Genome-wide expression profiling enabled the isolation of a number of Zac1 target genes known to regulate different aspects of β-cell function and peripheral insulin sensitivity. Among these, upregulation of Pparγ and Tcf4 impairs insulin-secretion and β-cell proliferation. Similarly, Zac1-mediated upregulation of Socs3 may attenuate β-cell proliferation and survival by inhibition of growth factor signalling. Additionally, Zac1 directly represses Pac1 and Rasgrf1 with roles in insulin secretion and β-cell proliferation. Collectively, concerted dysregulation of these target genes could contribute to the onset and course of TNDM1. Interestingly, Zac1 overexpression in β-cells spares the effects of stimulatory G-protein signaling on insulin secretion and raises the prospect for tailored treatments in relapsed TNDM1 patients. Overall, these results suggest that progress on the molecular and cellular foundations of monogenetic forms of diabetes can advance personalized therapy in addition to deepening the understanding of insulin and glucose metabolism in general.

  17. Neonatal and obstetric outcomes in diet- and insulin-treated women with gestational diabetes mellitus : a retrospective study

    NARCIS (Netherlands)

    Koning, Sarah H; Hoogenberg, Klaas; Baas, Mick G; Korteweg, Fleurisca J; Sollie, Krystyna M; Schering, Bertine J; van Loon, Aren J; Wolffenbuttel, Bruce H R; van den Berg, Paul P; Lutgers, Helen L

    2016-01-01

    BACKGROUND: To evaluate the neonatal and obstetric outcomes of pregnancies complicated by gestational diabetes mellitus (GDM). Screening and treatment - diet-only versus additional insulin therapy - were based on the 2010 national Dutch guidelines. METHODS: Retrospective study of the electronic medi

  18. High risk of neonatal complications in children of mothers with gestational diabetes mellitus in their first pregnancy

    DEFF Research Database (Denmark)

    Wielandt, Hanne; Schønemann-Rigel, Helena; Blunck, Charlotte H.;

    2015-01-01

    Introduction: The study presents the neonatal outcome from a cohort of women with gestational diabetes mellitus (GDM) in their first pregnancy. Methods: During a five-year period (2009-2013), a prospective follow-up study was performed at the Department of Gynaecology and Obstetrics, Lillebaelt...

  19. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia

    DEFF Research Database (Denmark)

    Hardies, Katia; de Kovel, Carolien G F; Weckhuysen, Sarah

    2015-01-01

    . Occasionally recessive mutations are identified: a recent publication described a distinct neonatal epileptic encephalopathy (MIM 615905) caused by autosomal recessive mutations in the SLC13A5 gene. Here, we report eight additional patients belonging to four different families with autosomal recessive...

  20. Recovery from diabetes in neonatal mice after a low-dose streptozotocin treatment

    Energy Technology Data Exchange (ETDEWEB)

    Kataoka, Masateru; Kawamuro, Yuki; Shiraki, Nobuaki [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); Miki, Rika; Sakano, Daisuke [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); The Global COE Cell Fate Regulation Research and Education Unit, Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); Yoshida, Tetsu; Yasukawa, Takanori; Kume, Kazuhiko [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); Kume, Shoen, E-mail: skume@kumamoto-u.ac.jp [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); The Global COE Cell Fate Regulation Research and Education Unit, Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan)

    2013-01-18

    Highlights: ► We monitored long-term beta cell regeneration in neonatal mice treated with low dose STZ. ► Low-dose STZ neonatal female mice recovered blood glucose in 150 days. ► Glucose intolerance of the STZ treated mice significantly improved in 150 days. -- Abstract: Administration of streptozotocin (STZ) induces destruction of β-cells and is widely used as an experimental animal model of type I diabetes. In neonatal rat, after low-doses of STZ-mediated destruction of β-cells, β-cells regeneration occurs and reversal of hyperglycemia was observed. However, in neonatal mice, β-cell regeneration seems to occur much slowly compared to that observed in the rat. Here, we described the time dependent quantitative changes in β-cell mass during a spontaneous slow recovery of diabetes induced in a low-dose STZ mice model. We then investigated the underlying mechanisms and analyzed the cell source for the recovery of β-cells. We showed here that postnatal day 7 (P7) female mice treated with 50 mg/kg STZ underwent the destruction of a large proportion of β-cells and developed hyperglycemia. The blood glucose increased gradually and reached a peak level at 500 mg/dl on day 35–50. This was followed by a spontaneous regeneration of β-cells. A reversal of non-fasting blood glucose to the control value was observed within 150 days. However, the mice still showed impaired glucose tolerance on day 150 and day 220, although a significant improvement was observed on day 150. Quantification of the β-cell mass revealed that the β-cell mass increased significantly between day 100 and day 150. On day 150 and day 220, the β-cell mass was approximately 23% and 48.5% of the control, respectively. Of the insulin-positive cells, 10% turned out to be PCNA-positive proliferating cells. Our results demonstrated that, β-cell duplication is one of the cell sources for β-cell regeneration.

  1. Infantile onset diabetes mellitus in developing countries - India

    OpenAIRE

    Varadarajan, Poovazhagi

    2016-01-01

    Infantile onset diabetes mellitus (IODM) is an uncommon metabolic disorder in children. Infants with onset of diabetes mellitus (DM) at age less than one year are likely to have transient or permanent neonatal DM or rarely type 1 diabetes. Diabetes with onset below 6 mo is a heterogeneous disease caused by single gene mutations. Literature on IODM is scanty in India. Nearly 83% of IODM cases present with diabetic keto acidosis at the onset. Missed diagnosis was common in infants with diabetes...

  2. A Neonate with persistent hypoglycemia and seizures.

    African Journals Online (AJOL)

    resource ptior countries in terms of investigation arid management ... of gestation or insulin dependent diabetic mellitus. The blood .... H Mutations in the Kir6,2 gene also cause ... neonatal development : studies with peri fusio n of pa nc real ic.

  3. Marfan syndrome with neonatal progeroid syndrome-like lipodystrophy associated with a novel frameshift mutation at the 3' terminus of the FBN1-gene.

    Science.gov (United States)

    Graul-Neumann, Luitgard M; Kienitz, Tina; Robinson, Peter N; Baasanjav, Sevjidmaa; Karow, Benjamin; Gillessen-Kaesbach, Gabriele; Fahsold, Raimund; Schmidt, Hartmut; Hoffmann, Katrin; Passarge, Eberhard

    2010-11-01

    We report on a 25-year-old woman with pronounced generalized lipodystrophy and a progeroid aspect since birth, who also had Marfan syndrome (MFS; fulfilling the Ghent criteria) with mild skeletal features, dilated aortic bulb, dural ectasia, bilateral subluxation of the lens, and severe myopia in addition to the severe generalized lipodystrophy. She lacked insulin resistance, hypertriglyceridemia, hepatic steatosis, and diabetes. Mutation analysis in the gene encoding fibrillin 1 (FBN1) revealed a novel de novo heterozygous deletion, c.8155_8156del2 in exon 64. The severe generalized lipodystrophy in this patient with progeroid features has not previously been described in other patients with MFS and FBN1 mutations. We did not find a mutation in genes known to be associated with congenital lipodystrophy (APGAT2, BSCL2, CAV1, PTRF-CAVIN, PPARG, LMNB2) or with Hutchinson-Gilford progeria (ZMPSTE24, LMNA/C). Other progeria syndromes were considered unlikely because premature greying, hypogonadism, and scleroderma-like skin disease were not present. Our patient shows striking similarity to two patients who have been published in this journal by O'Neill et al. [O'Neill et al. (2007); Am J Med Genet Part A 143A:1421-1430] with the diagnosis of neonatal progeroid syndrome (NPS). This condition also known as Wiedemann-Rautenstrauch syndrome is a rare disorder characterized by accelerated aging and lipodystrophy from birth, poor postnatal weight gain, and characteristic facial features. The course is usually progressive with early lethality. However this entity seems heterogeneous. We suggest that our patient and the two similar cases described before represent a new entity, a subgroup of MFS with overlapping features to NPS syndrome.

  4. Intrafamilial Variability of Early-Onset Diabetes due to an INS Mutation

    DEFF Research Database (Denmark)

    Fredheim, Siri; Svensson, Jannet; Pörksen, Sven

    2011-01-01

    Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS) gene. Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule....... The father, insulin treated for over 40 years, has bilateral preproliferative retinopathy. Conclusions. These three cases further confirm the essential features of diabetes caused by INS mutations with proteotoxic effect. We conclude that patients with similar features must be investigated for mutations...... of INS gene....

  5. Intrafamilial Variability of Early-Onset Diabetes due to an INS Mutation

    DEFF Research Database (Denmark)

    Fredheim, Siri; Svensson, Jannet; Pørksen, Sven

    2011-01-01

    Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS) gene. Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule...... children. The father, insulin treated for over 40 years, has bilateral preproliferative retinopathy. Conclusions. These three cases further confirm the essential features of diabetes caused by INS mutations with proteotoxic effect. We conclude that patients with similar features must be investigated...... for mutations of INS gene....

  6. STUDY ON THE RELATIONSHIP BETWEEN MITOCHONDRIAL GENE MUTATION AND LATENT AUTOIMMUNE DIABETES MELLITUS IN ADULTS

    Institute of Scientific and Technical Information of China (English)

    崔璨; 李强; 张一娜; 张巾超

    2002-01-01

    Objective.To identify the A3243G mutation of mitochondrial(mt) DNA in patients with latent autoimmune diabetes mellitus in adults (LADA) of Han nationality in the northeast area of China. Methods.Seventy nine diabetics of Han nationality,whose families have resided in the northeast area of China for more than 3 generations,were divided into 3 groups: Group 1 (22 cases of type 2 diabetes with maternal inheritance history),Group 2 (34 cases of LADA),Group 3 (23 cases of type 1 diabetes in adolescents).The A3243G of mt DNA was detected in these 79 subjects with the method of PCR RFLP. Results.None of the 79 diabetics studied was positively identified for the A3243G mutation of mt DNA. Conclusion.The A3243G mutation of mt DNA might not be related to the onset of LADA in diabetic population of Han nationality in northeast area of China and there might not be close relationship between A3243G mutation of mt DNA and autoimmunity.

  7. High risk of neonatal complications in children of mothers with gestational diabetes mellitus in their first pregnancy

    DEFF Research Database (Denmark)

    Wielandt, Hanne Benedicte; Schønemann-Rigel, Helena; Holst, Charlotte Blunck

    2015-01-01

    intensive care unit. CONCLUSION: The present study supports the notion of high-risk pregnancy among GDM patients. Compared with nulliparous in general, the offspring were more likely to be delivered by emergency CS. Despite the prophylactic procedures, one in six had neonatal hypoglycaemia.......INTRODUCTION: THE study presents the neonatal outcome from a cohort of women with gestational diabetes mellitus (GDM) in their first pregnancy. METHODS: During a five-year period (2009-2013), a prospective follow-up study was performed at the Department of Gynaecology and Obstetrics, Lillebaelt...

  8. Neonatal levels of adiponectin, interleukin-10 and interleukin-12 are associated with the risk of developing type 1 diabetes in childhood and adolescence

    DEFF Research Database (Denmark)

    Thorsen, Steffen U.; Pipper, Christian B.; Eising, Stefanie

    2016-01-01

    BACKGROUND/AIM: An in-depth understanding of the early phase of type 1 diabetes (T1D) pathogenesis is important for targeting primary prevention. We examined if 14 preselected mediators of immune responses differed in neonates that later developed T1D compared to control neonates. METHODS...

  9. Gestational diabetes mellitus diagnosed in different periods of gestation and neonatal outcome

    Directory of Open Access Journals (Sweden)

    Aqueela Ayaz

    2009-01-01

    Full Text Available Objective: To evaluate the maternal and neonatal out-comes in women diagnosed as gestational diabetes mel-litus (GDM in different periods of pregnancy.Materials and Methods: This descriptive observational study was carried out from 1st January 2007 to 31th De-cember 2007 in the department of Obstetrics and Gyne-cology of a 1300 bedded tertiary care hospital "Bahawal Victoria Hospital" in Bahawalpur, Pakistan. Seventy six pregnant women met the inclusion criteria of diabetes diagnosed on the basis of the Oral glucose tolerance test (OGTT according to the National Diabetic Data Group. The study subjects were divided on the basis of gestational age at the first time diagnosis of GDM in the current pregnancy into group A (gestational age 13-23 weeks, group B (24-30 weeks and group C (31-36 weeks.Results: Out of total study subjects, 19 (25% were di-agnosed as GDM between 13-23 weeks of gestation (early-onset, 25 (32.9% between 24-30 weeks while 32 (42.1% diagnosed in the gestational age of 31-35 weeks (late-onset. Pregnancy-induced hypertension 5 (26.3%, polyhydramnios 5 (26.3% and insulin treat-ment 13 (68.4% were higher in women with earlier GDM diagnosis (p<0.05. APGAR score at 5-min below seven was seen in 3 (15.8%, large for gestational age in 5 (26.3%, respiratory distress in 6 (31.5% and pre-term delivery in 5 (26.3% of the early GDM group. These complications were seen more frequently in the early group compared with late-onset GDM group (p<0.05. Conclusion: Earlier diagnosis of GDM was seem to be associated with less favorable newborn outcome.

  10. Screening for mtDNA diabetes mutations in Pima Indians with NIDDM

    Energy Technology Data Exchange (ETDEWEB)

    Sepehrnia, B.; Prezant, T.R.; Rotter, J.I. [UCLA School of Medicine, Los Angeles, CA (United States)] [and others

    1995-03-27

    More than half of the Pima Indians over age 35 years have non-insulin-dependent (type II) diabetes mellitus (NIDDM). Extensive data indicate the importance of maternal diabetes in determining their risk for diabetes. Generally, the risk of having NIDDM is higher in patients with affected mothers than affected fathers. This has been attributed to intrauterine factors, but recently mitochondrial inheritance has been raised as an alternative hypothesis. In other populations, several families and individuals with diabetes due to a mitochondrial DNA point mutation at nucleotide 3243 in the tRNA{sup leu(UUR)} gene have been described, as has one family with a 10.4 kb mitochondrial DNA duplication/deletion. We tested whether these specific mitochondrial gene mutations could explain a portion of the excess maternal transmission seen in the Pima Indians. Mitochondrial DNA obtained from blood lymphocytes of 148 Pima Indians with NIDDM was screened both for the point mutation at nt 3243, and the 10.4 kb duplication/deletion. Neither of these mutations was detected, and although a small proportion of the excess maternal transmission in Pima Indians could still be due to yet undescribed mitochondrial mutations or imprinted nuclear genes, our data support the role of the intrauterine environment in this population. 32 refs, 21 figs.

  11. Prenatal/neonatal pathology in two cases of Cornelia de Lange syndrome harboring novel mutations of NIPBL.

    Science.gov (United States)

    Lalatta, Faustina; Russo, Silvia; Gentilin, Barbara; Spaccini, Luigina; Boschetto, Chiara; Cavalleri, Florinda; Masciadri, Maura; Gervasini, Cristina; Bentivegna, Angela; Castronovo, Paola; Larizza, Lidia

    2007-03-01

    This study reviews prenatal findings in two cases with a suspected diagnosis of Cornelia de Lange Syndrome, a multisystem disorder characterized by somatic defects and mental retardation, that were later confirmed by postmortem examination and molecular testing. Although the correlation between the Cornelia de Lange Syndrome genotype and phenotype is still unclear, preliminary data indicate several severe phenotypic features that are likely to be detected prenatally in NIPBL-mutated patients. We report on two prenatal/neonatal cases with unusual pathologic findings indicating Cornelia de Lange Syndrome. The first, with suspected Cornelia de Lange Syndrome after a set of typical dysmorphisms was noted by prenatal ultrasound, was confirmed by a physical examination after termination of the pregnancy. The second was diagnosed neonatally on the basis of typical clinical signs. Medical complications led to death within the first month of life. Molecular analysis of NIPBL, the gene that codes for delangin (a component of the cohesin complex), performed postnatally detected two de novo mutations: a missense change (P2056L) in a highly conserved residue and a nonsense alteration (S2490 replaced by a stop codon). We suggest that early diagnosis of Cornelia de Lange Syndrome would be made much easier by the assemblage of a set of prenatal diagnostic features and criteria in Cornelia de Lange Syndrome cases that have been confirmed by direct physical and molecular examinations. We also suggest that Cornelia de Lange Syndrome genotype-phenotype correlations need to be extended to prenatal cases.

  12. Whole exome sequencing identifies de novo heterozygous CAV1 mutations associated with a novel neonatal onset lipodystrophy syndrome.

    Science.gov (United States)

    Garg, Abhimanyu; Kircher, Martin; Del Campo, Miguel; Amato, R Stephen; Agarwal, Anil K

    2015-08-01

    Despite remarkable progress in identifying causal genes for many types of genetic lipodystrophies in the last decade, the molecular basis of many extremely rare lipodystrophy patients with distinctive phenotypes remains unclear. We conducted whole exome sequencing of the parents and probands from six pedigrees with neonatal onset of generalized loss of subcutaneous fat with additional distinctive phenotypic features and report de novo heterozygous null mutations, c.424C>T (p.Q142*) and c.479_480delTT (p.F160*), in CAV1 in a 7-year-old male and a 3-year-old female of European origin, respectively. Both the patients had generalized fat loss, thin mottled skin and progeroid features at birth. The male patient had cataracts requiring extraction at age 30 months and the female patient had pulmonary arterial hypertension. Dermal fibroblasts of the female patient revealed negligible CAV1 immunofluorescence staining compared to control but there were no differences in the number and morphology of caveolae upon electron microscopy examination. Based upon the similarities in the clinical features of these two patients, previous reports of CAV1 mutations in patients with lipodystrophies and pulmonary hypertension, and similar features seen in CAV1 null mice, we conclude that these variants are the most likely cause of one subtype of neonatal onset generalized lipodystrophy syndrome.

  13. Neonatal detection of the 35delG mutation of the GJB2 gene in families at risk for deafness.

    Science.gov (United States)

    Bathelier, C; François, M; Lucotte, G

    2004-01-01

    About half of congenitally deaf children that have a recessively inherited sensorineural deafness are born from normal-hearing parents and have no risk factor for hearing loss. Mutation 35delG in the connexin-26 gene is in European populations the basis for around half of all recessively inherited prelingual sensorineural deafness. The aim of our study was to assess the efficacy and utility of the 35delG mutation of the connexin-26 gene analysis for neonates at familial risk, from DNA isolated from Guthrie newborn screening cards. Newborns who had consanguineous parent and/or a familial history of deafness underwent connexin-26 gene analysis from DNA isolated from Guthrie cards and two hearing screening tests (transient evoked otoacoustic emissions, and auditory brainstem recordings). 24 newborns were includes in this pilot study; one of them is homozygous for the 35delG mutation and had abnormal hearing screening tests; all the others newborns had normal connexin gene and at least one normal hearing screening test. Detection on connexin-26 gene mutation is feasible in selected at-risk newborns on one additional blood spot on Guthrie card.

  14. Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13 mutations among thai infants

    Directory of Open Access Journals (Sweden)

    Treepongkaruna Suporn

    2012-10-01

    Full Text Available Abstract Background The most common causes of cholestatic jaundice are biliary atresia and idiopathic neonatal hepatitis (INH. Specific disorders underlying INH, such as various infectious and metabolic causes, including neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD especially, in East Asian populations are increasingly being identified. Since most NICCD infants recovered from liver disease by 1 year of age, they often are misdiagnosed with INH, leading to difficulty in determining the true prevalence of NICCD. Mutation(s of human SLC25A13 gene encoding a mitochondrial aspartate/glutamate carrier isoform 2 (AGC2, can lead to AGC2 deficiency, resulting in NICCD and an adult-onset fatal disease namely citrullinemia type II (CTLN2. To study the prevalence of NICCD and SLC25A13 mutations in Thai infants, and to compare manifestations of NICCD and non-NICCD, infants with idiopathic cholestatic jaundice or INH were enrolled. Clinical and biochemical data were reviewed. Urine organic acid and plasma amino acids profiles were analyzed. PCR-sequencing of all 18 exons of SLC25A13 and gap PCR for the mutations IVS16ins3kb and Ex16+74_IVS17-32del516 were performed. mRNA were analyzed in selected cases with possible splicing error. Results Five out of 39 (12.8% unrelated infants enrolled in the study were found to have NICCD, of which three had homozygous 851del4 (GTATdel and two compound heterozygous 851del4/IVS16ins3kb and 851del4/1638ins23, respectively. Two missense mutations (p.M1? and p.R605Q of unknown functional significance were identified. At the initial presentation, NICCD patients had higher levels of alkaline phosphatase (ALP and alpha-fetoprotein (AFP and lower level of alanine aminotransferase (ALT than those in non-NICCD patients (pp Conclusion NICCD should be considered in infants with idiopathic cholestasis. The preliminary estimated prevalence of NICCD was calculated to be 1/48,228 with carrier rate of 1/110 among

  15. Pedigree analysis of a child with neonatal diabetes%1例新生儿糖尿病患者家系基因分析

    Institute of Scientific and Technical Information of China (English)

    吴瑛婷; 余永国; 陈慧芬; 郁婷婷; 王剑; 杨培蓉; 丁宇; 黄晓东; 沈永年; 傅启华

    2013-01-01

    Objectives To investigate KCNJ11, ABCC8 and INS gene mutations of a child with neonatal diabetes. Methods Genomic DNA was extracted from the peripheral blood of the patient. All exons and the flanking sequences of KCNJ11, ABCC8 and INS gene were amplified by PCR, and the PCR products were directly sequenced. Results c.67A>AG, p.23K>K/E and c.1009G>GA, p.337V>V/I variants in KCNJ11 gene were characterized in the proband. Conclusions c.67A>AG, p.23K>K/ E and c.1009G>GA, p.337V>V/I may be associated with permanent neonatal diabetes. Genetic analysis has a very significant value for the therapeutic regimen and genetic counseling of neonatal diabetes.%目的 对1 例新生儿糖尿病患儿进行KCNJ11、ABCC8 及INS 基因突变检测.方法 对1 例新生儿糖尿病患儿进行基因组DNA 抽提,用PCR 方法扩增KCNJ11、ABCC8 及INS 基因的所有外显子,通过基因直接测序分析该例患儿的基因突变及多态性.结果 该例患儿KCNJ11 基因中存在2 个致病性多态性位点c.67A>AG,p.23K>K/E 和c.1009G>GA,p.337V>V/I.结论 KCNJ11 基因c.67A>AG,p.23K>K/E 和c.1009G>GA,p.337V>V/I 变异与新生儿永久性糖尿病相关,进行致病基因的遗传学分析,对于该病的临床分型、治疗方案的确立及遗传学咨询均有着重要的指导意义.

  16. Loss-of-function mutations in SLC30A8 protect against type 2 diabetes

    DEFF Research Database (Denmark)

    Flannick, Jason; Thorleifsson, Gudmar; Beer, Nicola L.

    2014-01-01

    Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating va...

  17. A novel splice site mutation in neonatal carnitine palmitoyl transferase II deficiency.

    NARCIS (Netherlands)

    Smeets, R.J.P.; Smeitink, J.A.M.; Semmekrot, B.A.; Scholte, H.R.; Wanders, R.J.; Heuvel, L.P.W.J. van den

    2003-01-01

    Mitochondrial beta-oxidation of long-chain fatty acids requires the concerted action of three tightly integrated membrane-bound enzymes (carnitine palmitoyltransferase I and II and carnitine/acylcarnitine translocase) that transport them into mitochondria. Neonatal onset of carnitine palmitoyltransf

  18. Genetic analysis of neonatal diabetes mellitus and its influence on treatment outcome%新生儿糖尿病致病基因分析及其对疗效的影响

    Institute of Scientific and Technical Information of China (English)

    陈秀丽; 程若倩; 赵诸慧; 支涤静; 沈水仙; 罗飞宏; 章淼滢; 李堂; 陈临琪; 胡敏; 杜虹; 曹凌峰

    2011-01-01

    Fourteen neonatal diabetes mellitus(NDM)patients were recruited. 9 patients were treated with glyburide and the other 5 with insulin. ABCC8, KCNJ11, and INS genes were sequenced in 6 of them. Gene mutations were found in 2, 1, and 1 cases in these genes, respectively. One case with 6q24 hypomethylation and another without known mutation were also found. 8 out of 9 patients treated with glyburide reached euglycemia(88.9%). The other 5 patients with insulin therapy either died or lost contact. The results suggest that glyburide therapy is effective in neonatal diabetes mellitus, while insulin therapy may contribute to poor compliance.%14例新生儿糖尿病(neonatal diabetes mellitus)入选,比较胰岛素(n=5)和格列本脲(n=9)的疗效.扩增6例患儿KCNJ11、ABCC8、INS基因并测序.共发现2例存在ABCC8基因突变,1例KCNJ11基因突变,1例为INS基因突变,1例为6q24甲基化减低,1例突变基因不清.9例新生儿糖尿病格列本脲治疗者8例血糖控制良好(88.9%).5例采用胰岛素治疗后均失访或死亡.提示新生儿糖尿病胰岛素治疗依从性差,格列本脲可有效降低血糖.

  19. Congenital nephrogenic diabetes insipidus with a novel mutation in the aquaporin 2 gene.

    Science.gov (United States)

    Park, Youn Jong; Baik, Haing Woon; Cheong, Hae Il; Kang, Ju Hyung

    2014-07-01

    Congenital nephrogenic diabetes insipidus (CNDI) is a rare disorder caused by mutations of the arginine vasopressin (AVP) V2 receptor or aquaporin 2 (AQP2) genes. The current study presented the case of CNDI in a 1-month-old male with a novel mutation in the AQP2 gene. The patient was referred due to the occurrence of hypernatremia and mild-intermittent fever since birth. An AVP stimulation test was compatible with CNDI as there was no significant response to desmopressin. Molecular genetic analysis demonstrated two mutations in exon 1 of the AQP2 gene: C to T transition, which resulted in a missense mutation of (108)Thr (ACG) to Met (ATG); and a 127, 128 delCA, which resulted in a deletion mutation of glutamine in position 43 at codon CAG as the first affected amino acid, with the new reading frame endign in a termination codon at position 62. The molecular genetic analysis of the parents showed that the missense mutation was inherited maternally and the deletion mutation was inherited paternally. The parents showed no signs or symptoms of CNDI, indicating autosomal recessive inheritance. The (108)Thr (ACG) to Met (ATG) mutation was confirmed as a novel mutation. Therefore, the molecular identification of the AQP2 gene has clinical significance, as early recognition of CNDI in infants that show only non-specific symptoms, can be facilitated. Thus, repeated episodes of dehydration, which may cause physical and mental retardation can be avoided.

  20. Molecular Basis of Transient Neonatal Zinc Deficiency: NOVEL ZnT2 MUTATIONS DISRUPTING ZINC BINDING AND PERMEATION.

    Science.gov (United States)

    Golan, Yarden; Itsumura, Naoya; Glaser, Fabian; Berman, Bluma; Kambe, Taiho; Assaraf, Yehuda G

    2016-06-24

    A gradually increasing number of transient neonatal zinc deficiency (TNZD) cases was recently reported, all of which were associated with inactivating ZnT2 mutations. Here we characterized the impact of three novel heterozygous ZnT2 mutations G280R, T312M, and E355Q, which cause TNZD in exclusively breastfed infants of Japanese mothers. We used the bimolecular fluorescence complementation (BiFC) assay to provide direct visual evidence for the in situ dimerization of these ZnT2 mutants, and to explore their subcellular localization. Moreover, using three complementary functional assays, zinc accumulation using BiFC-Zinquin and Zinpyr-1 fluorescence as well as zinc toxicity assay, we determined the impact of these ZnT2 mutations on vesicular zinc accumulation. Although all three mutants formed homodimers with the wild type (WT) ZnT2 and retained substantial vesicular localization, as well as vesicular zinc accumulation, they had no dominant-negative effect over the WT ZnT2. Furthermore, using advanced bioinformatics, structural modeling, and site-directed mutagenesis we found that these mutations localized at key residues, which play an important physiological role in zinc coordination (G280R and E355Q) and zinc permeation (T312M). Collectively, our findings establish that some heterozygous loss of function ZnT2 mutations disrupt zinc binding and zinc permeation, thereby suggesting a haploinsufficiency state for the unaffected WT ZnT2 allele in TNZD pathogenesis. These results highlight the burning need for the development of a suitable genetic screen for the early diagnosis of TNZD to prevent morbidity.

  1. Cardiac abnormalities in diabetic patients with mutation in the mitochondrial tRNA {sup Leu(UUR)}Gene

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Hiroshi [Hyogo Medical Center for Adults, Akashi (Japan); Shiotani, Hideyuki

    1999-11-01

    An A-to-G transition at position 3243 of the mitochondrial DNA is known to be a pathogenic factor for mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), diabetes and cardiomyopathy. This mutation causes dysfunction of the central nervous system in MELAS. Because the heart, as well as the brain and nervous system, is highly dependent on the energy produced by mitochondrial oxidation, these tissues are more vulnerable to mitochondrial defects. Cardiac abnormalities were assessed in 10 diabetic patients associated with this mutation using echocardiography and {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy, and compared with 19 diabetic patients without the mutation. Duration of diabetes, therapy, control of blood glucose and diabetic complications, such as diabetic retinopathy and nephropathy, were not different between the 2 groups. Diabetic patients with the mutation had a significantly thicker interventricular septum (16.8{+-}3.7 vs 11.0{+-}1.6 mm, p<0.001) than those without the mutation. Fractional shortening was lower in diabetic patients with the mutation than those without it (30.7{+-}7.0 vs 42.5{+-}6.6, p<0.001). MIBG uptake on the delayed MIBG image was significantly lower in diabetic patients with the mutation than in those without the mutation (mean value of the heart to mediastinum ratio: 1.6{+-}0.2 vs 2.0{+-}0.4, p>0.05). In conclusion, left ventricular hypertrophy with or without abnormal wall motion and severely reduced MIBG uptake may be characteristic in diabetic patients with a mutation in the mitochondrial tRNA {sup Leu(UUR)} gene. (author)

  2. Pregnancy and neonatal outcomes in IndigenousAustralians with diabetes in pregnancy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To perform a systematic review of reportedneonatal and pregnancy outcomes of IndigenousAustralians with diabetes in pregnancy (DIP).METHODS: Electronic searches of PubMed and Web ofScience were carried out. Articles were selected if theycontained original data on DIP outcomes in IndigenousAustralians. There were no specific exclusion criteria.RESULTS: A total of eight articles, predominantly fromQueensland and Western Australia were identifiedonce inclusion criteria were applied. Birth data frommidwifery registries or paper charts encompassingyears 1985-2008 were used. A total of 465591 pregnantwomen with and without DIP were included in the eightstudies, with 1363 being Indigenous women with DIP.Indigenous Australians experienced increased ratesof many known adverse outcomes of DIP including:macrosomia, caesarean section, congenital deformities,low birth weight, hypoglycaemia, and neonatal trauma.There were regional differences among IndigenousAustralians, particularly regional/remote vs metropolitanpopulations where the regional/remote data showedworse outcomes. Two of the articles did not note adifference between Aboriginals and Caucasians inthe rates of measured adverse outcome. Studiesvaried significantly in size, measured outcomes, andsubsequent analysis.CONCLUSION: The health disparities between IndigenousAustralians and non-Indigenous Australiansare further evidenced by poorer outcomes in DIP.This has broader implications for Indigenous health ingeneral.

  3. Transient neonatal diabetes mellitus with macroglossia diagnosed by methylation specific PCR (MS-PCR

    Directory of Open Access Journals (Sweden)

    Hye Young Jin

    2010-03-01

    Full Text Available Transient neonatal diabetes mellitus (TNDM has been associated with paternal uniparental isodisomy of chromosome 6, paternally inherited duplication of 6q24, or a methylation defect at a CpG island of the ZAC or HYMAI gene. We experienced a case of TNDM in which the patient presented with hyperglycemia, macroglossia, and intrauterine growth retardation, caused by a paternally derived HYMAI. An 18-day-old female infant was admitted to the hospital because of macroglossia and recurrent hyperglycemia. In addition to the macroglossia, she also presented with large fontanelles, micrognathia, and prominent eyes. Serum glucose levels were 200&#8211;300 mg/dL and they improved spontaneously 2 days after admission. To identify the presence of a maternal methylated allele, bisulfite-treated genomic DNA from peripheral blood was prepared and digested with BssHII after polymerase chain reaction (PCR amplification with methylation-specific HYMAI primers. PCR and restriction fragment length polymorphism analysis showed that the patient had only the paternal origin of the HYMA1 gene. TNDM is associated with a methylation defect in chromosome 6, suggesting that an imprinted gene on chromosome 6 is responsible for this phenotype.

  4. Reduced Tyk2 gene expression in β-cells due to natural mutation determines susceptibility to virus-induced diabetes

    OpenAIRE

    Izumi, Kenichi; Mine, Keiichiro; Inoue, Yoshitaka; Teshima, Miho; Ogawa, Shuichiro; Kai, Yuji; Kurafuji, Toshinobu; Hirakawa, Kanako; Miyakawa, Daiki; Ikeda, Haruka; Inada, Akari; Hara, Manami; Yamada, Hisakata; Akashi, Koichi; Niho, Yoshiyuki

    2015-01-01

    Accumulating evidence suggests that viruses play an important role in the development of diabetes. Although the diabetogenic encephalomyocarditis strain D virus induces diabetes in restricted lines of inbred mice, the susceptibility genes to virus-induced diabetes have not been identified. We report here that novel Tyrosine kinase 2 (Tyk2) gene mutations are present in virus-induced diabetes-sensitive SJL and SWR mice. Mice carrying the mutant Tyk2 gene on the virus-resistant C57BL/6 backgrou...

  5. [Neonatal renal vein thrombosis in a heterozygous carrier of both factor V Leiden and the MTHFR gene mutation].

    Science.gov (United States)

    Wannes, S; Soua, H; Ghanmi, S; Braham, H; Hassine, M; Hamza, H A; Ben Hamouda, H; Sfar, M-T

    2012-04-01

    Renal vein thrombosis (RVT) is a rare but potentially serious neonatal disease. Its epidemiology and its clinical and biological expression are currently well known, but its etiological exploration, like that of venous thromboembolism, is increasingly complex. Perinatal risk factors such as prematurity, dehydration, and birth asphyxia have lost their direct accountability at the expense of their interaction with constitutional disorders of hemostasis. We report a case of RVT in a newborn who was a heterozygous carrier of both factor V Leiden and the methylene tetrahydrofolate reductase (MTHFR) gene mutation. We recall the clinical and epidemiological characteristics. A search for inborn blood coagulation disorders should be systematic in the newborn infant with venous thrombosis because of the risk of recurrence, taking into account perinatal factors and maternal thrombophilia (especially if RVT is established during the prenatal period).

  6. N-acetylglutamate synthase deficiency: Novel mutation associated with neonatal presentation and literature review of molecular and phenotypic spectra

    Directory of Open Access Journals (Sweden)

    Eiman H. Al Kaabi

    2016-09-01

    Full Text Available The urea cycle is the main pathway for the disposal of excess nitrogen. Carbamoylphosphate synthetase 1 (CPS1, the first and rate-limiting enzyme of urea cycle, is activated by N-acetylglutamate (NAG, and thus N-acetylglutamate synthase (NAGS is an essential part of the urea cycle. Although NAGS deficiency is the rarest urea cycle disorder, it is the only one that can be specifically and effectively treated by a drug, N-carbamylglutamate, a stable structural analogous of NAG that activates CPS1. Here we report an infant with NAGS deficiency who presented with neonatal hyperammonemia. She was found to have a novel homozygous splice-site mutation, c.1097-2A>T, in the NAGS gene. We describe the clinical course of this infant, who had rapid response to N-carbamylglutamate treatment. In addition, we reviewed the clinical and molecular spectra of previously reported individuals with NAGS deficiency, which presents in most cases with neonatal hyperammonemia, and in some cases the presentation is later, with a broad spectrum of ages and manifestations. With this broad later-onset phenotypic spectrum, maintaining a high index of suspicion is needed for the early diagnosis of this treatable disease.

  7. N-acetylglutamate synthase deficiency: Novel mutation associated with neonatal presentation and literature review of molecular and phenotypic spectra.

    Science.gov (United States)

    Al Kaabi, Eiman H; El-Hattab, Ayman W

    2016-09-01

    The urea cycle is the main pathway for the disposal of excess nitrogen. Carbamoylphosphate synthetase 1 (CPS1), the first and rate-limiting enzyme of urea cycle, is activated by N-acetylglutamate (NAG), and thus N-acetylglutamate synthase (NAGS) is an essential part of the urea cycle. Although NAGS deficiency is the rarest urea cycle disorder, it is the only one that can be specifically and effectively treated by a drug, N-carbamylglutamate, a stable structural analogous of NAG that activates CPS1. Here we report an infant with NAGS deficiency who presented with neonatal hyperammonemia. She was found to have a novel homozygous splice-site mutation, c.1097-2A>T, in the NAGS gene. We describe the clinical course of this infant, who had rapid response to N-carbamylglutamate treatment. In addition, we reviewed the clinical and molecular spectra of previously reported individuals with NAGS deficiency, which presents in most cases with neonatal hyperammonemia, and in some cases the presentation is later, with a broad spectrum of ages and manifestations. With this broad later-onset phenotypic spectrum, maintaining a high index of suspicion is needed for the early diagnosis of this treatable disease.

  8. A Frame-Shift Mutation in CAV1 Is Associated with a Severe Neonatal Progeroid and Lipodystrophy Syndrome.

    Science.gov (United States)

    Schrauwen, Isabelle; Szelinger, Szabolcs; Siniard, Ashley L; Kurdoglu, Ahmet; Corneveaux, Jason J; Malenica, Ivana; Richholt, Ryan; Van Camp, Guy; De Both, Matt; Swaminathan, Shanker; Turk, Mari; Ramsey, Keri; Craig, David W; Narayanan, Vinodh; Huentelman, Matthew J

    2015-01-01

    A 3-year-old female patient presenting with an unknown syndrome of a neonatal progeroid appearance, lipodystrophy, pulmonary hypertension, cutis marmorata, feeding disorder and failure to thrive was investigated by whole-genome sequencing. This revealed a de novo, heterozygous, frame-shift mutation in the Caveolin1 gene (CAV1) (p.Phe160X). Mutations in CAV1, encoding the main component of the caveolae in plasma membranes, cause Berardinelli-Seip congenital lipodystrophy type 3 (BSCL). Although BSCL is recessive, heterozygous carriers either show a reduced phenotype of partial lipodystrophy, pulmonary hypertension, or no phenotype. To investigate the pathogenic mechanisms underlying this syndrome in more depth, we performed next generation RNA sequencing of peripheral blood, which showed several dysregulated pathways in the patient that might be related to the phenotypic progeroid features (apoptosis, DNA repair/replication, mitochondrial). Secondly, we found a significant down-regulation of known Cav1 interaction partners, verifying the dysfunction of CAV1. Other known progeroid genes and lipodystrophy genes were also dysregulated. Next, western blotting of lysates of cultured fibroblasts showed that the patient shows a significantly decreased expression of wild-type CAV1 protein, demonstrating a loss-of-function mutation, though her phenotype is more severe that other heterozygotes with similar mutations. This phenotypic variety could be explained by differences in genetic background. Indications for this are supported by additional rare variants we found in AGPAT2 and LPIN1 lipodystrophy genes. CAV1, AGPAT2 and LPIN1 all play an important role in triacylglycerol (TAG) biosynthesis in adipose tissue, and the defective function in different parts of this pathway, though not all to the same extend, could contribute to a more severe lipoatrophic phenotype in this patient. In conclusion, we report, for the first time, an association of CAV1 dysfunction with a syndrome

  9. Anti-diabetic effects of ethanol extract of Bryonia laciniosa seeds and its saponins rich fraction in neonatally streptozotocin-induced diabetic rats

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    Sandip B Patel

    2015-01-01

    Full Text Available Context: Bryonia laciniosa Linn. (Cucurbitaceae seed is used in traditional medicine for a number of ailments including metabolic disorders. Aim: This study evaluated the anti-diabetic action of the ethanol extract of B. laciniosa seeds and saponin fraction of it through its effect on hyperglycemia, dyslipidaemia and oxidative stress in neonatally streptozotocin (n-STZ-induced diabetic rats (n-STZ diabetic rats. Materials and Methods: Ethanol extract (250 and 500 mg/kg; p.o., saponin fraction (100 and 200 mg/kg; p.o. and standard drug glibenclamide (3 mg/kg; p.o. were administered to diabetic rats when the rats were 6 weeks old and continued for 10 consecutive weeks. Effects of ethanol extract and saponin fraction on various biochemical parameters were studied in diabetic rats. Results: The treatment with ethanol extract and saponin fraction for 10 weeks decrease in the levels of glucose, triglycerides, cholesterol, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, serum urea, serum creatinine and diminished activities of aspartate transaminase, and alanine transaminase. The anti-hyperglycemic nature of B. laciniosa is probably brought about by the extra- the pancreatic mechanism as evidenced from unchanged levels of plasma insulin. B. laciniosa modulated effect of diabetes on the liver malondialdehyde, reduced glutathione (GSH, superoxide dismutase (SOD, and catalase (CAT activity. Administration of ethanol extract and saponin fraction to diabetic rats showed a significant reversal of disturbed antioxidant status. Significant increase in SOD, CAT, and levels of GSH was observed in treated n-STZ diabetic rats. Conclusion: The present study reveals the efficacy of B. laciniosa seed extract and its saponin fraction in the amelioration of n-STZ diabetic rats.

  10. Neonatal outcomes in women with gestational diabetes mellitus treated with metformin in compare with insulin: A randomized clinical trial

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    Safura Ruholamin

    2014-01-01

    Full Text Available Background: The objective of this study was to compare neonatal outcomes in women with gestational diabetes mellitus (GDM treated with either metformin or insulin. Materials and Methods: A randomized clinical trial carried out on year 2011 on 109 women with GDM who did not adequately control by dietary measures. They received metformin 500 mg once or twice daily or insulin 0.2 IU/kg/day initially. The dose was titrated to achieve target blood glucose values. Neonatal outcomes such as hypoglycemia, birth weight, Apgar score, umbilical artery pH, and hyperbilirubinemia in the 50 women who remained exclusively on metformin were compared with 50 women who treated with insulin. Results: Two groups were similar in mean fasting blood sugar (P = 0.7 and postprandial measurements (P = 0.8 throughout GDM treatment. Pregnancy complications or preterm labor were not different significantly between two groups. Considering neonatal outcomes between insulin and metformin groups, such as hypoglycemia (2 [4%] and 0 [0%], respectively, birth weight (3342 ± 506 mg and 3176 ± 438 mg, respectively, 5 th min Apgar score <7 (no one in either group, umbilical artery pH <7.05 (no one in either group and hyperbilirubinemia (1 [2%] and 0 [0%], respectively, no significant statistical differences were seen. Conclusion: Based on these preliminary data, considering neonatal outcomes, metformin appears to be a safe as insulin in the treatment of GDM.

  11. Gestational diabetes mellitus treatment reduces obesity-induced adverse pregnancy and neonatal outcomes: the St. Carlos gestational study

    Science.gov (United States)

    Assaf-Balut, Carla; Familiar, Cristina; García de la Torre, Nuria; Rubio, Miguel A; Bordiú, Elena; del Valle, Laura; Lara, Miriam; Ruiz, Teresa; Ortolá, Ana; Crespo, Irene; Duran, Alejandra; Herraiz, Miguel A; Izquierdo, Nuria; Perez, Noelia; Torrejon, Maria J; Runkle, Isabelle; Montañez, Carmen; Calle-Pascual, Alfonso L

    2016-01-01

    Background Obesity and gestational diabetes mellitus (GDM) increase the morbidity of the mother and newborn, which could increase further should they coexist. We aimed to determine the risk of adverse pregnancy and neonatal outcomes associated with excess weight (EW), and within this group identify potential differences between those with and without GDM. Methods We carried out a post-hoc analysis of the St. Carlos Gestational Study which included 3312 pregnant women, arranged in 3 groups: normal-weight women (NWw) (2398/72.4%), overweight women (OWw) (649/19.6%) and obese women (OBw) (265/8%). OWw and OBw were grouped as EW women (EWw). We analyzed variables related to adverse pregnancy and neonatal outcomes. Results The relative risk (95% CI) for GDM was 1.82 (1.47 to 2.25; p90th centile, newborns admitted to neonatal intensive care unit (NICU), instrumental delivery and cesarean delivery (all p<0.005). Multivariate analysis, adjusted for parity and ethnicity, showed that EW increased the risk of prematurity, admission to NICU, cesarean and instrumental delivery, especially in EWw without GDM. NWw with GDM had a significantly lower risk of admission to NICU and cesarean delivery, compared with NWw without GDM. Conclusions EW is detrimental for pregnancy and neonatal outcomes, and treatment of GDM contributes to lowering the risk in EWw and NWw. Applying the same lifestyle changes to all pregnant women, independent of their weight or GDM condition, could improve these outcomes. PMID:28074143

  12. Loss-of-Function Mutations in APPL1 in Familial Diabetes Mellitus

    Science.gov (United States)

    Prudente, Sabrina; Jungtrakoon, Prapaporn; Marucci, Antonella; Ludovico, Ornella; Buranasupkajorn, Patinut; Mazza, Tommaso; Hastings, Timothy; Milano, Teresa; Morini, Eleonora; Mercuri, Luana; Bailetti, Diego; Mendonca, Christine; Alberico, Federica; Basile, Giorgio; Romani, Marta; Miccinilli, Elide; Pizzuti, Antonio; Carella, Massimo; Barbetti, Fabrizio; Pascarella, Stefano; Marchetti, Piero; Trischitta, Vincenzo; Di Paola, Rosa; Doria, Alessandro

    2015-01-01

    Diabetes mellitus is a highly heterogeneous disorder encompassing several distinct forms with different clinical manifestations including a wide spectrum of age at onset. Despite many advances, the causal genetic defect remains unknown for many subtypes of the disease, including some of those forms with an apparent Mendelian mode of inheritance. Here we report two loss-of-function mutations (c.1655T>A [p.Leu552∗] and c.280G>A [p.Asp94Asn]) in the gene for the Adaptor Protein, Phosphotyrosine Interaction, PH domain, and leucine zipper containing 1 (APPL1) that were identified by means of whole-exome sequencing in two large families with a high prevalence of diabetes not due to mutations in known genes involved in maturity onset diabetes of the young (MODY). APPL1 binds to AKT2, a key molecule in the insulin signaling pathway, thereby enhancing insulin-induced AKT2 activation and downstream signaling leading to insulin action and secretion. Both mutations cause APPL1 loss of function. The p.Leu552∗ alteration totally abolishes APPL1 protein expression in HepG2 transfected cells and the p.Asp94Asn alteration causes significant reduction in the enhancement of the insulin-stimulated AKT2 and GSK3β phosphorylation that is observed after wild-type APPL1 transfection. These findings—linking APPL1 mutations to familial forms of diabetes—reaffirm the critical role of APPL1 in glucose homeostasis. PMID:26073777

  13. A Newly-Discovered Mutation in the RFX6 Gene of the Rare Mitchell-Riley Syndrome

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    Khan, Nusrat; Dandan, Waleed; Al Hassani, Noura; Hadi, Suha

    2016-01-01

    Mitchell-Riley syndrome is a genetic disorder characterized by neonatal diabetes, pancreatic hypoplasia, intestinal atresia and/or malrotation, biliary atresia, and gallbladder aplasia or hypoplasia. It was considered a variant of the Martinez-Frias syndrome with similar phenotypic characteristics, except for neonatal diabetes and tracheoesophageal fistula. However, the genetic mutation in (regulatory factor X on chromosome 6) RFX6 was only detected in babies who had diabetes, making it different from the previously known mutations for the disease. This is the first reported case of a classical Mitchell-Riley syndrome in the Arab peninsula along with additional features and novel mutations in the RFX6 gene. PMID:26761945

  14. Atypical Neonatal Marfan Syndrome with p.Glu1073Lys Mutation of FBN1: the First Case in Korea

    Science.gov (United States)

    2017-01-01

    Neonatal Marfan syndrome (nMFS) is considered to be on the most severe end of the spectrum of type I fibrillinopathies. The common features of nMFS include ascending aortic dilatation, severe mitral and/or tricuspid valve insufficiency, ectopia lentis, arachnodactyly, joint contractures, crumpled ear, loose skin, and pulmonary emphysema.We describe a newborn male diagnosed with nMFS. He presented several atypical features, such as diaphragmatic eventration, severe hydronephrosis with hydroureter, and dilated cisterna magna. Molecular analysis revealed a missense mutation at nucleotide 3217 (c.3217G>A) in exon 26 of the fibrillin-1 (FBN1) gene, resulting in the substitution of a glutamate for a lysine at codon 1073 (E1073K) in the 12th calcium binding epidermal growth factor-like domain of the FBN1 protein. Here we report a rare case of Nmfs with several combined atypical features, such as diaphragmatic eventration, severe hydronephrosis with hydroureter, and dilated cisterna magna. Our report is the first atypical nMFS case with p.Glu1073Lys mutation of FBN1 in Korea and may help clinicians with the diagnosis and follow-up of atypical nMFS. PMID:27914124

  15. Partial nephrogenic diabetes insipidus caused by a novel mutation in the AVPR2 gene

    DEFF Research Database (Denmark)

    Færch, Mia; Christensen, Jane H; Corydon, Thomas J

    2008-01-01

    and polyuria since infancy. Initial clinical testing confirmed a diagnosis of diabetes insipidus (DI). Urine osmolarity rose during fluid deprivation and after 20 microg of intranasal desmopressin [1-deamino-8-d-arginine-vasopressin (dDAVP)]. A similar DI phenotype was found in his brother. Methods The coding...... output. Discussion The affected members of this Belgian kindred have CNDI with partial resistance to AVP caused by a mutation in the AVPR2 gene that differs from any of the six mutations reported previously to produce this phenotype. Because the resistance to AVP is partial, this form of CNDI can...

  16. Identification of a SIRT1 mutation in a family with type 1 diabetes

    DEFF Research Database (Denmark)

    Biason-Lauber, Anna; Böni-Schnetzler, Marianne; Hubbard, Basil P

    2013-01-01

    Type 1 diabetes is caused by autoimmune-mediated β cell destruction leading to insulin deficiency. The histone deacetylase SIRT1 plays an essential role in modulating several age-related diseases. Here we describe a family carrying a mutation in the SIRT1 gene, in which all five affected members....... Direct and exome sequencing identified the presence of a T-to-C exchange in exon 1 of SIRT1, corresponding to a leucine-to-proline mutation at residue 107. Expression of SIRT1-L107P in insulin-producing cells resulted in overproduction of nitric oxide, cytokines, and chemokines. These observations...... identify a role for SIRT1 in human autoimmunity and unveil a monogenic form of type 1 diabetes....

  17. Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality.

    Science.gov (United States)

    Belet, Stefanie; Fieremans, Nathalie; Yuan, Xuan; Van Esch, Hilde; Verbeeck, Jelle; Ye, Zhaohui; Cheng, Linzhao; Brodsky, Brett R; Hu, Hao; Kalscheuer, Vera M; Brodsky, Robert A; Froyen, Guy

    2014-03-01

    The phosphatidylinositol glycan class A (PIGA) protein is a member of the glycosylphosphatidylinositol anchor pathway. Germline mutations in PIGA located at Xp22.2 are thought to be lethal in males. However, a nonsense mutation in the last coding exon was recently described in two brothers with multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2) who survived through birth likely because of the hypomorphic nature of the truncated protein, but died in their first weeks of life. Here, we report on a frameshift mutation early in the PIGA cDNA (c.76dupT; p.Y26Lfs*3) that cosegregates with the disease in a large family diagnosed with a severe syndromic form of X-linked intellectual disability. Unexpectedly, CD59 surface expression suggested the production of a shorter PIGA protein with residual functionality. We provide evidence that the second methionine at position 37 may be used for the translation of a 36 amino acids shorter PIGA. Complementation assays confirmed that this shorter PIGA cDNA was able to partially rescue the surface expression of CD59 in a PIGA-null cell line. Taken together, our data strongly suggest that the early frameshift mutation in PIGA produces a truncated hypomorph, which is sufficient to rescue the lethality in males but not the MCAHS2-like phenotype.

  18. Hepatocyte nuclear factor 1-alpha mutation in normal glucose-tolerant subjects and early-onset type 2 diabetic patients.

    Science.gov (United States)

    Lim, Dong Mee; Huh, Nam; Park, Keun Yong

    2008-12-01

    The prevalence of diabetes in Korea is reported to be approximately 10%, but cases of maturity-onset diabetes of the young (MODY) are rare in Korea. A diagnostic technique for autosomal dominant MODY is being actively sought. In this regard, we used a DNA chip to investigate the frequency of mutations of the MODY3 gene (hepatocyte nuclear factor-1alpha) in Korean patients with early-onset type 2 diabetes. The genomic DNA of 30 normal individuals [age, 24.9+/-8.6 years] and 25 patients with early-onset type 2 diabetes (age, 27+/-5.9 years) was extracted, and the MODY3 gene was amplified. The amplified DNA was hybridized onto a MODY3 chip, which has oligonucleotides of 15-25 bases, representing wild-type and mutant MODY3 sequences in both forward and reverse orientations, immobilized on its surface. Among the normal subjects, there was no mutation of MODY3. Among those with early-onset type 2 diabetes, there was one case of MODY3 mutation. Our results indicate that MODY3 mutations are not rare in Korean early-onset type 2 diabetes patients in Korea and suggest that MODY3 mutations in patients with early-onset type 2 diabetes need to be further evaluated.

  19. HANAC Syndrome Col4a1 Mutation Causes Neonate Glomerular Hyperpermeability and Adult Glomerulocystic Kidney Disease.

    Science.gov (United States)

    Chen, Zhiyong; Migeon, Tiffany; Verpont, Marie-Christine; Zaidan, Mohamad; Sado, Yoshikazu; Kerjaschki, Dontscho; Ronco, Pierre; Plaisier, Emmanuelle

    2016-04-01

    Hereditary angiopathy, nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is an autosomal dominant syndrome caused by mutations in COL4A1 that encodes the α1 chain of collagen IV, a major component of basement membranes. Patients present with cerebral small vessel disease, retinal tortuosity, muscle cramps, and kidney disease consisting of multiple renal cysts, chronic kidney failure, and sometimes hematuria. Mutations producing HANAC syndrome localize within the integrin binding site containing CB3[IV] fragment of the COL4A1 protein. To investigate the pathophysiology of HANAC syndrome, we generated mice harboring the Col4a1 p.Gly498Val mutation identified in a family with the syndrome. Col4a1 G498V mutation resulted in delayed glomerulogenesis and podocyte differentiation without reduction of nephron number, causing albuminuria and hematuria in newborns. The glomerular defects resolved within the first month, but glomerular cysts developed in 3-month-old mutant mice. Abnormal structure of Bowman's capsule was associated with metalloproteinase induction and activation of the glomerular parietal epithelial cells that abnormally expressed CD44,α-SMA, ILK, and DDR1. Inflammatory infiltrates were observed around glomeruli and arterioles. Homozygous Col4a1 G498V mutant mice additionally showed dysmorphic papillae and urinary concentration defects. These results reveal a developmental role for the α1α1α2 collagen IV molecule in the embryonic glomerular basement membrane, affecting podocyte differentiation. The observed association between molecular alteration of the collagenous network in Bowman's capsule of the mature kidney and activation of parietal epithelial cells, matrix remodeling, and inflammation may account for glomerular cyst development and CKD in patients with COL4A1-related disorders.

  20. A novel compound heterozygous mutation in an adolescent with insulin-dependent diabetes: The challenge of characterizing Wolfram syndrome.

    Science.gov (United States)

    Maltoni, Giulio; Minardi, Raffaella; Cristalli, Carlotta Pia; Nardi, Laura; D'Alberton, Franco; Mantovani, Vilma; Zucchini, Stefano

    2016-11-01

    WS diagnosis is often delayed since misdiagnosed as autoimmune diabetes. The rarity of the condition and the absence of other diseases at diabetes diagnosis might make extremely challenging the recognition of WS. However the novel compound heterozygosity for the here reported mutations, seems to confer a mild phenotype among the spectrum of WS manifestations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Autosomal inheritance of diabetes in two families characterized by obesity and a novel H241Q mutation in NEUROD1

    DEFF Research Database (Denmark)

    Gonsorcíková, Lucie; Pruhová, Stepánka; Cinek, Ondrej;

    2008-01-01

    BACKGROUND: The aim of the study was to search for mutations in the NEUROD1 and IPF-1 genes in patients with clinical characteristics of maturity-onset diabetes of the young (MODY) but with no mutations in the HNF-4A (MODY1), GCK (MODY2) and TCF1 (MODY3) genes. METHODS: We studied 30 unrelated...

  2. A Frame-Shift Mutation in CAV1 Is Associated with a Severe Neonatal Progeroid and Lipodystrophy Syndrome.

    Directory of Open Access Journals (Sweden)

    Isabelle Schrauwen

    Full Text Available A 3-year-old female patient presenting with an unknown syndrome of a neonatal progeroid appearance, lipodystrophy, pulmonary hypertension, cutis marmorata, feeding disorder and failure to thrive was investigated by whole-genome sequencing. This revealed a de novo, heterozygous, frame-shift mutation in the Caveolin1 gene (CAV1 (p.Phe160X. Mutations in CAV1, encoding the main component of the caveolae in plasma membranes, cause Berardinelli-Seip congenital lipodystrophy type 3 (BSCL. Although BSCL is recessive, heterozygous carriers either show a reduced phenotype of partial lipodystrophy, pulmonary hypertension, or no phenotype. To investigate the pathogenic mechanisms underlying this syndrome in more depth, we performed next generation RNA sequencing of peripheral blood, which showed several dysregulated pathways in the patient that might be related to the phenotypic progeroid features (apoptosis, DNA repair/replication, mitochondrial. Secondly, we found a significant down-regulation of known Cav1 interaction partners, verifying the dysfunction of CAV1. Other known progeroid genes and lipodystrophy genes were also dysregulated. Next, western blotting of lysates of cultured fibroblasts showed that the patient shows a significantly decreased expression of wild-type CAV1 protein, demonstrating a loss-of-function mutation, though her phenotype is more severe that other heterozygotes with similar mutations. This phenotypic variety could be explained by differences in genetic background. Indications for this are supported by additional rare variants we found in AGPAT2 and LPIN1 lipodystrophy genes. CAV1, AGPAT2 and LPIN1 all play an important role in triacylglycerol (TAG biosynthesis in adipose tissue, and the defective function in different parts of this pathway, though not all to the same extend, could contribute to a more severe lipoatrophic phenotype in this patient. In conclusion, we report, for the first time, an association of CAV1 dysfunction

  3. Central diabetes insipidus: alert for dehydration in very low birth weight infants during the neonatal period. A case report

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    Maria Lúcia Silveira Ferlin

    Full Text Available CONTEXT: Central diabetes insipidus (CDI is a rare cause of hypernatremia during the neonatal period. The diagnosis is particularly difficult in very low birth weight (VLBW newborns. CASE REPORT: We report on a preterm newborn who presented CDI soon after birth. On the third day of life, signs of dehydration were present despite normal fluid supply. The diuresis rate was 4.4 ml/kg/h. Although the fluid supply was then increased, the dehydration continued, with hypernatremia, normal glycemia, diuresis of 7.4 ml/kg/h and urine density of 1005 mOsmol/l. Thus, a diagnostic hypothesis of diabetes insipidus was raised. A test with a nasal vasopressin analogue (dDAVP was performed and CDI was confirmed. Reduction of the fluid supply became possible through appropriate treatment. CONCLUSION: The diagnosis of CDI is rarely made during the neonatal period, especially in VLBW newborns, because of the difficulty in detecting elevated diuresis. Persistent hypernatremia, usually accompanied by hyperthermia despite abundant fluid supply, weight loss and low urine osmolality are important signs of alert.

  4. Mutations in COA6 cause cytochrome c oxidase deficiency and neonatal hypertrophic cardiomyopathy.

    Science.gov (United States)

    Baertling, Fabian; A M van den Brand, Mariel; Hertecant, Jozef L; Al-Shamsi, Aisha; P van den Heuvel, Lambert; Distelmaier, Felix; Mayatepek, Ertan; Smeitink, Jan A; Nijtmans, Leo G J; Rodenburg, Richard J T

    2015-01-01

    COA6/C1ORF31 is involved in cytochrome c oxidase (complex IV) biogenesis. We present a new pathogenic COA6 variant detected in a patient with neonatal hypertrophic cardiomyopathy and isolated complex IV deficiency. For the first time, clinical details about a COA6-deficient patient are given and patient fibroblasts are functionally characterized: COA6 protein is undetectable and steady-state levels of complex IV and several of its subunits are reduced. The monomeric COX1 assembly intermediate accumulates. Using pulse-chase experiments, we demonstrate an increased turnover of mitochondrial encoded complex IV subunits. Although monomeric complex IV is decreased in patient fibroblasts, the CI/CIII2 /CIVn -supercomplexes remain unaffected. Copper supplementation shows a partial rescue of complex IV deficiency in patient fibroblasts. We conclude that COA6 is required for complex IV subunit stability. Furthermore, the proposed role in the copper delivery pathway to complex IV subunits is substantiated and a therapeutic lead for COA6-deficient patients is provided.

  5. A neonatal encephalopathy with seizures in standard poodle dogs with a missense mutation in the canine ortholog of ATF2.

    Science.gov (United States)

    Chen, Xuhua; Johnson, Gary S; Schnabel, Robert D; Taylor, Jeremy F; Johnson, Gayle C; Parker, Heidi G; Patterson, Edward E; Katz, Martin L; Awano, Tomoyuki; Khan, Shahwanaz; O'Brien, Dennis P

    2008-02-01

    Neonatal encephalopathy with seizures (NEWS) is a previously undescribed autosomal recessive disease of standard poodle puppies. Affected puppies are small and weak at birth. Many die in their first week of life. Those surviving past 1 week develop ataxia, a whole-body tremor, and, by 4 to 6 weeks of age, severe generalized clonic-tonic seizures. None have survived to 7 weeks of age. Cerebella from affected puppies were reduced in size and often contained dysplastic foci consisting of clusters of intermixed granule and Purkinje neurons. We used deoxyribonucleic acid samples from related standard poodles to map the NEWS locus to a 2.87-Mb segment of CFA36, which contains the canine ortholog of ATF2. This gene encodes activating transcription factor 2 (ATF-2), which participates in the cellular responses to a wide variety of stimuli. We amplified and sequenced all coding regions of canine ATF2 from a NEWS-affected puppy and identified a T > G transversion that predicts a methionine-to-arginine missense mutation at amino acid position 51. Methionine-51 lies within a hydrophobic docking site for mitogen-activated protein kinases that activate ATF-2 so the arginine substitution is likely to interfere with ATF-2 activation. All 20 NEWS-affected puppies in the standard poodle family were homozygous for the mutant G allele. The 58 clinically normal family members were either G/T heterozygotes or homozygous for the ancestral T allele. There are no previous reports of spontaneous ATF2 mutations in people or animals; however, atf2-knockout mice have cerebellar lesions that are similar to those in puppies with NEWS.

  6. Comparison of glibenclamide and insulin on neonatal outcomes in pregnant women with gestational diabetes

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    Mitra Behrashi

    2016-01-01

    Conclusions: The results of this study revealed that glibenclamide is able to reduce the risk of fetal macrosomia without increasing neonatal anomalies, jaundice, hypocalcemia, infant respiratory distress, and NICU admission.

  7. Identification of five novel arginine vasopressin gene mutations in patients with familial neurohypophyseal diabetes insipidus.

    Science.gov (United States)

    Tian, Dan; Cen, Jing; Nie, Min; Gu, Feng

    2016-10-01

    Familial neurohypophyseal diabetes insipidus (FNDI) is a genetic disorder presenting with polyuria and polydipsia and is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The clinical manifestations of this disorder vary greatly depending on different mutations. The present study reports the genetic, clinical and biochemical characteristics of patients with FNDI caused by five novel mutations. Ten patients encompassing two pedigrees and four individual cases diagnosed with FNDI were included. Biochemical markers and magnetic resonance imaging (MRI) were evaluated and genomic DNA was sequenced. The results revealed that age at onset ranged from 1.0 to 11.0 years. Daily urine volumes ranged from 2.0 to 12.0 liters. One patient had mental retardation and three patients had puberty retardation; one patient had nausea, vomiting and mental retardation; and two patients had fever. Treatments, if given, included desmopressin and vasopressin tannate. Posterior pituitary T1-weighted MRI high-intensity signals were absent in two cases and present in four cases. Sequencing revealed five novel mutations in the AVP-NPII gene. On the whole, the findings of the present study indicate that FNDI exhibits different clinical manifestations and a diverse age at onset. Posterior pituitary MRI does not provide a definite diagnosis of FNDI. We also identified five novel AVP-NPII mutations. Thus, an enhanced understanding of FNDI pathogenesis may provide a basis for the development of presymptomatic FNDI diagnotic tools.

  8. Methyltetrahydrofolate reductase C677T gene mutation and hyperhomocysteinemia as a novel risk factor for diabetic nephropathy.

    Science.gov (United States)

    Ukinc, Kubilay; Ersoz, Halil Onder; Karahan, Caner; Erem, Cihangir; Eminagaoglu, Selcuk; Hacihasanoglu, Arif Bayram; Yilmaz, Mustafa; Kocak, Mustafa

    2009-10-01

    Hyperhomocysteinemia is a well-defined risk factor for endothelial dysfunction and atherosclerosis. A point mutation (677 C-T) of MTHFR gene results in a significant increase at plasma homocysteine levels. In this study we aimed to evaluate the effects of MTHFR gene mutation and consequent hyperhomocysteinemia on the development of diabetic microvascular complications in comparison with the other defined risk factors. Diabetic patients without a history of macrovascular complication or overt nephropathy enrolled into the study. The presence of MTHFR 677 C-T point mutation was evaluated by Real-Time PCR technique by using a LightCycler. MTHFR heterozygous mutation was present in 24 patients over 52. Patients with diabetes were divided into two groups according to the presence of MTHFR gene mutation. Both groups were well matched regarding age and diabetes duration. Metabolic parameters, plasma homocysteine, microalbuminuria, folic acid, and vitamin B12 levels were also studied. Presence of neuropathy and retinopathy were evaluated by specific tests. Duration of diabetes, BMI, systolic and diastolic blood pressure, plasma CRP, HbA1c, and lipid levels were not different between the two groups. Plasma homocysteine (12.89 +/- 1.74 and 8.98 +/- 1.91 micromol/l; P diabetic nephropathy had MTHFR gene mutation, while this was only 27% (8 over 30) in normoalbuminuric patients (P = 0.017). There was a significant correlation of plasma homocysteine level with microalbuminuria (r = 0.54; P = 0.031) in the patients with diabetic nephropathy who had C677T polymorphism. We did not find any specific association of MTHFR gene mutation and hyperhomocysteinemia with retinopathy or neuropathy.

  9. Prevalence of gestational diabetes and associated maternal and neonatal complications in a fast-developing community: global comparisons

    Directory of Open Access Journals (Sweden)

    Bener A

    2011-11-01

    Full Text Available Abdulbari Bener1,2, Najah M Saleh3, Abdulla Al-Hamaq41Department of Medical Statistics and Epidemiology, Hamad Medical Corporation, Hamad General Hospital, Department of Public Health and Medical Education, Weill Cornell Medical College, Qatar; 2Department of Evidence for Population Health Unit, School of Epidemiology and Health Sciences, University of Manchester, Manchester, UK; 3Department of Obstetrics and Gynecology, Women's Hospital, Hamad Medical Corporation, Qatar; 4Qatar Diabetes Association and Qatar Foundation, QatarBackground: The prevalence of gestational diabetes (GDM is increasing all over the world. Hence, the impact of GDM on maternal and infant health is an important topic of research. No study has been conducted in Qatar to evaluate the outcome of pregnancies complicated by diabetes mellitus.Objective: The aim of the study was to determine the prevalence of GDM, compare the maternal–neonatal complications among women with GDM and non-GDM pregnant women, and investigate the risk factors and potential outcomes associated with GDM.Design: This is a prospective cohort study.Setting: The survey was carried out at the antenatal clinics of the Women's Hospital, Qatar.Subjects and methods: A representative sample of 2056 pregnant women who attended the antenatal clinics of the Women's Hospital were surveyed during the period from the first week of January 2010 to April 2011. From this sample, 1608 women (78.2% expressed their consent to participate in the study. Questionnaires were administered to pregnant women who were seeking antenatal care at this urban hospital. The questionnaire covered variables related to sociodemographic factors, family history, medical history, maternal complications, and neonatal outcome.Results: The prevalence of GDM in Qatar was 16.3%. Women with GDM were significantly higher in the age group of 35–45 years (45%; P = 0.001. Family history of diabetes (31.7%; P < 0.001, increased parity (55.3%; P = 0

  10. Novel glucokinase mutation in a boy with maturity-onset diabetes of the young

    Directory of Open Access Journals (Sweden)

    Milenković Tatjana

    2008-01-01

    Full Text Available INTRODUCTION Maturity-onset diabetes of the young (MODY is a heterogenous group of disorders characterized by an early onset of insulin-independent diabetes mellitus, an autosomal dominant mode of inheritance and a primary defect in beta-cell. There are six subtypes of MODY. MODY2 and MODY3 are the most frequent. CASE OUTLINE We present a nine-year-old boy with intermittent hyperglycaemia. According to family history, the diagnosis of MODY2 was suspected. Molecular analysis revealed novel missense mutation R250c in exon 7 of glucokinase gene. Mutation (c.748 C>T is the result of substitution of aminoacid cysteine by arginine (p.Arg250Cys. This is the first pediatric patient with MODY2 in Serbia whose diagnosis is established at molecular level. CONCLUSION Molecular diagnosis of MODY has important consequences in terms of prognosis, therapy and family screening of the disorder. Investigation of other patients with MODY2 in our country is important to establish prevalence and nature of mutations in glucokinase gene.

  11. The effects of implementing the International Association of Diabetes and Pregnancy Study Groups criteria for diagnosing gestational diabetes on maternal and neonatal outcomes.

    Directory of Open Access Journals (Sweden)

    Tai-Ho Hung

    Full Text Available In 2010, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG recommended a new strategy for the screening and diagnosis of gestational diabetes mellitus (GDM. However, no study has indicated that adopting the IADPSG recommendations improves perinatal outcomes. The objective of this study was to evaluate the effects of implementing the IADPSG criteria for diagnosing GDM on maternal and neonatal outcomes.Previously, we used a two-step approach (a 1-h, 50-g glucose challenge test followed by a 3-h, 100-g glucose tolerance test when indicated to screen for and diagnose GDM. In July 2011, we adopted the IADPSG recommendations in our routine obstetric care. In this study, we retrospectively compared the rates of various maternal and neonatal outcomes in all women who delivered after 24 weeks of gestation during the periods before (P1, between January 1, 2009 and December 31, 2010 and after (P2, between January 1, 2012 and December 31, 2013 the IADPSG criteria were implemented. Pregnancies complicated by multiple gestations, fetal chromosomal or structural anomalies, and pre-pregnancy diabetes mellitus were excluded. Our results showed that the incidence of GDM increased from 4.6% using the two-step method to 12.4% using the IADPSG criteria. Compared to the women in P1, the women in P2 experienced less weight gain during pregnancy, lower birth weights, shorter labor courses, and lower rates of macrosomia (<4000 g and large-for-gestational age (LGA infants. P2 was a significant independent factor against macrosomia (adjusted odds ratio [OR] 0.63, 95% confidence interval [CI] 0.43-0.90 and LGA (adjusted OR 0.74, 95% CI 0.61-0.89 after multivariable logistic regression analysis.The adoption of the IADPSG criteria for diagnosis of GDM was associated with significant reductions in maternal weight gain during pregnancy, birth weights, and the rates of macrosomia and LGA.

  12. Role of molecular genetics in transforming diagnosis of diabetes mellitus.

    Science.gov (United States)

    Molven, Anders; Njølstad, Pål R

    2011-04-01

    Most common diseases also run in families as rare, monogenic forms. Diabetes is no exception. Mutations in approximately 20 different genes are now known to cause monogenic diabetes, a disease group that can be subclassified into maturity-onset diabetes of the young, neonatal diabetes and mitochondrial diabetes. In some families, additional features, such as urogenital malformations, exocrine pancreatic dysfunction and neurological abnormalities, are present and may aid the diagnostic classification. The finding of a mutation in monogenic diabetes may have implications for the prediction of prognosis and choice of treatment. Mutations in the GCK gene cause a mild form of diabetes, which seldom needs insulin and has a low risk for complications. By contrast, HNF1A mutations lead to a diabetes form that in severity, treatment and complication risk resembles Type 1 diabetes, although these patients may experience a good effect of sulfonylurea treatment. The majority of neonatal diabetes cases are caused by mutations in the K(ATP) channel genes ABCC8 and KCNJ11, and sulfonylurea therapy is then usually superior to insulin. Diseases with a considerable genetic component may now be explored by genome-wide approaches using next-generation DNA sequencing technology. We expect that within a few years important breakthroughs will be made in mapping cases of diabetes with a suspected, but still unsolved monogenic basis.

  13. Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules.

    Science.gov (United States)

    Leslie, Nancy; Wang, Xinjian; Peng, Yanyan; Valencia, C Alexander; Khuchua, Zaza; Hata, Jessica; Witte, David; Huang, Taosheng; Bove, Kevin E

    2016-03-01

    Complex I deficiency causes Leigh syndrome, fatal infant lactic acidosis, and neonatal cardiomyopathy. Mutations in more than 100 nuclear DNA and mitochondrial DNA genes miscode for complex I subunits or assembly factors. ACAD9 is an acyl-CoA dehydrogenase with a novel function in assembly of complex I; biallelic mutations cause progressive encephalomyopathy, recurrent Reye syndrome, and fatal cardiomyopathy. We describe the first autopsy in fatal neonatal lethal lactic acidosis due to mutations in ACAD9 that reduced complex I activity. We identified mitochondrial hyperplasia in cardiac myocytes, diaphragm muscle, and liver and renal tubules in formalin-fixed, paraffin-embedded tissue using immunohistochemistry for mitochondrial antigens. Whole-exome sequencing revealed compound heterozygous variants in the ACAD9 gene: c.187G>T (p.E63*) and c.941T>C (p.L314P). The nonsense mutation causes late infantile lethality; the missense variant is novel. Autopsy-derived fibroblasts had reduced complex I activity (53% of control) with normal activity in complexes II to IV, similar to reported cases of ACAD9 deficiency.

  14. New treatment paradigms in neonatal metabolic epilepsies.

    Science.gov (United States)

    Pearl, P L

    2009-04-01

    Neonatal seizures represent a major challenge among the epilepsies vis-à-vis seizure classification, electroclinical correlation, inherent excitability of neocortex, ontogenic characteristics of neurotransmitter receptors, and responsiveness to standard antiepileptic drugs. Each of these factors renders neonatal seizures more difficult to treat, and therapy has been a vexing area for recent advances in this seizure category. Conversely, specific metabolic disorders have very special therapeutic considerations in the clinical setting of neonatal seizures which require a high index of clinical suspicion and rapid intervention for a successful outcome. The prototype is pyridoxine dependency, although pyridoxal 5'-phosphate dependency is a recently recognized but treatable neonatal epilepsy that deserves earmarked distinction. Clinicians must remain vigilant for these possibilities, including atypical cases where apparent seizure-free intervals may occur. Folinic acid-dependent seizures are allelic with pyridoxine dependency. Serine-dependent seizures and glucose transporter deficiency may present with neonatal seizures and have specific therapy. A vital potassium channel regulated by serum ATP/ADP ratios in the pancreas and brain may be mutated with a resultant neuroendocrinopathy characterized by development delay, epilepsy, and neonatal diabetes (DEND). This requires oral hypoglycaemic therapy, and not insulin, for neurological responsiveness. The startle syndrome of hyperekplexia, which mimics neonatal epilepsy, has been associated with laryngospasm and sudden death but is treated with benzodiazepines.

  15. Mutations in MODY Genes Are not Common Cause of Early-Onset Type 2 Diabetes in Mexican Families

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    Bravo-Ríos LE

    2005-05-01

    Full Text Available CONTEXT: Maturity-onset diabetes of the young (MODY is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset and a primary insulin secretion defect. Certain MODY gene sequence variants may be involved in polygenic forms of type 2 diabetes. OBJECTIVE: We assessed the contribution of MODY genes to the etiology of type 2 early-onset diabetes in 23 Mexican families, including five with apparently autosomal dominant inheritance. PATIENTS: Twenty-three unrelated Mexican families with early-onset type 2 diabetes previously screened for the presence of glucokinase mutations, were studied. DESIGN: We screened MODY genes for sequence variants by PCR-SSCP analysis and automated sequencing. We performed a functional analysis of the HNF-1alpha P379H recombinant protein in vitro in both HeLa and RINm5f beta-cell lines. MAIN OUTCOME MEASURES: MODY gene mutation screening and P379H mutant protein transactivation assay. RESULTS: No mutations were detected in the HNF-4alpha, IPF-1, NEUROD1 or HNF-1beta genes in any of the families studied. A new mutation (P379H of the HNF-1alpha gene was identified in one MODY family. RINm5f and HeLa cell transfection assays revealed decreased transactivation activity of the mutant protein on the human insulin promoter. CONCLUSIONS: All known MODY genes were screened for abnormalities in this cohort of early-onset diabetes families which included 5 MODY pedigrees. We identified a new HNF-1alpha MODY mutation (P379H and demonstrated that it reduces the transactivation potential of the mutant protein on the human insulin promoter. No other mutation was identified in this cohort indicating that abnormalities in MODY genes are generally not a common cause of early-onset diabetes and this includes MODY families in Mexico.

  16. No Association between Loss-of-Function Mutations in filaggrin and Diabetes, Cardiovascular Disease, and All-Cause Mortality

    Science.gov (United States)

    Husemoen, Lise Lotte N.; Skaaby, Tea; Jørgensen, Torben; Thyssen, Jacob P.; Meldgaard, Michael; Szecsi, Pal B.; Stender, Steen; Johansen, Jeanne Duus; Linneberg, Allan

    2013-01-01

    Background Common loss-of-function mutations in the filaggrin gene (FLG) are a major predisposing risk factor for atopic disease due to reduced epidermal filaggrin protein levels. We previously observed an association between these mutations and type 2 diabetes and hypothesized that an inherited impairment of skin barrier functions could facilitate low-grade inflammation and hence increase the risk of diabetes and cardiovascular disease. We examined the association between loss-of-function mutations in FLG and diabetes, stroke, ischemic heart disease (IHD), and all-cause mortality in the general population. Methods The R501X and 2282del4 loss-of function mutations in FLG were genotyped in four Danish study populations including a total of 13373 adults aged 15-77 years. Two of the studies also genotyped the R2447X mutation. By linkage to Danish national central registers we obtained information for all participants on dates of diagnoses of diabetes, stroke, and IHD, as well as all-cause mortality. Data were analyzed by Cox proportional hazard models and combined by fixed effect meta-analyses. Results In meta-analyses combining the results from the four individual studies, carriage of loss-of-function mutations in FLG was not associated with incident diabetes (hazard ratio (HR) (95% confidence intervals (CI)) = 0.95 (0.73, 1.23), stroke (HR (95% CI) = 1.27 (0.97, 1.65), ischemic heart disease (HR (95%CI) = 0.92 (0.71, 1.19), and all-cause mortality (HR (95%CI) = 1.02 (0.83, 1.25)). Similar results were obtained when including prevalent cases in logistic regression models. Conclusion Our results suggest that loss-of-function mutations in FLG are not associated with type 2 diabetes, cardiovascular disease, and all-cause mortality. However, larger studies with longer follow-up are needed to exclude any associations. PMID:24367652

  17. No association between loss-of-function mutations in filaggrin and diabetes, cardiovascular disease, and all-cause mortality.

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    Lise Lotte N Husemoen

    Full Text Available BACKGROUND: Common loss-of-function mutations in the filaggrin gene (FLG are a major predisposing risk factor for atopic disease due to reduced epidermal filaggrin protein levels. We previously observed an association between these mutations and type 2 diabetes and hypothesized that an inherited impairment of skin barrier functions could facilitate low-grade inflammation and hence increase the risk of diabetes and cardiovascular disease. We examined the association between loss-of-function mutations in FLG and diabetes, stroke, ischemic heart disease (IHD, and all-cause mortality in the general population. METHODS: The R501X and 2282del4 loss-of function mutations in FLG were genotyped in four Danish study populations including a total of 13373 adults aged 15-77 years. Two of the studies also genotyped the R2447X mutation. By linkage to Danish national central registers we obtained information for all participants on dates of diagnoses of diabetes, stroke, and IHD, as well as all-cause mortality. Data were analyzed by Cox proportional hazard models and combined by fixed effect meta-analyses. RESULTS: In meta-analyses combining the results from the four individual studies, carriage of loss-of-function mutations in FLG was not associated with incident diabetes (hazard ratio (HR (95% confidence intervals (CI = 0.95 (0.73, 1.23, stroke (HR (95% CI = 1.27 (0.97, 1.65, ischemic heart disease (HR (95%CI = 0.92 (0.71, 1.19, and all-cause mortality (HR (95%CI = 1.02 (0.83, 1.25. Similar results were obtained when including prevalent cases in logistic regression models. CONCLUSION: Our results suggest that loss-of-function mutations in FLG are not associated with type 2 diabetes, cardiovascular disease, and all-cause mortality. However, larger studies with longer follow-up are needed to exclude any associations.

  18. [Monogenic form of diabetes mellitus due to HNF4α mutation (MODY-1) - the first case in Hungary].

    Science.gov (United States)

    Jermendy, György; Balogh, István; Gaál, Zsolt

    2016-03-20

    The classification of diabetes mellitus in adolescents and young adults is often difficult. The diagnosis of the monogenic form of diabetes may have substantial influence on quality of life, prognosis and the choice of the appropriate treatment of affected patients. Among MODY (maturity-onset of diabetes in the young) MODY-1 is rarely detected, only 13 families were described in 2000, and 103 different mutations in 173 families were known in 2013 worldwide. The authors present the first Hungarian case of a monogenic form of diabetes due to HNF4α mutation (MODY-1). The diabetes of the index patient No. 1 (42-year-old woman with insulin treated diabetes) was diagnosed as gestational diabetes at age of 20 when she was treated with diet only. Later, insulin treatment has been initiated when marked hyperglycaemia was detected during an episode of acute pneumonia at age of 26. The diabetes of the index patient No. 2 (20-year-old daughter of the index patient No. 1, treated also with insulin) was diagnosed as type 2 diabetes at age of 13 and the patient was treated with diet only. Later the classification was modified to type 1 and insulin therapy was initiated at age of 14. The manifestation of diabetes, the familial occurrence and the low dose insulin requirement were suggestive for monogenic diabetes. Using molecular genetic method a mutation (c.869G>A, p.R290H) of HNF4α gene was found and MODY-1 was diagnosed in both cases. Insulin therapy was switched to treatment with low dose sulfanylurea and an excellent glycaemic control was achieved and sustained at follow-up of 1-year. No further positive cases were found during screening of other family members.

  19. Research progress of relationship between mutations of insulin gene and diabetes mellitus%胰岛素基因突变与糖尿病关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    李灿; 刘丽梅

    2013-01-01

    Insulin is the unique hypoglycemic hormone which is secreted by islet β-cells. Insulin gene mutations could result in insulinopathies, permanent neonatal diabetes mellitus ( PNDM), maturity onset diabetes of the young ( MODY) and auto-antibodies-negative type 1 diabetes mellitus. The research progress of relationship between mutations of insulin gene and diabetes mellitus is reviewed in this article.%胰岛素是由胰岛β细胞分泌的体内惟一的降糖激素.胰岛素基因突变可以导致异常胰岛素病、永久性新生儿糖尿病(PNDM)、青少年成人起病型糖尿病(MODY)以及部分自身抗体阴性的1型糖尿病.文章就胰岛素基因突变与糖尿病关系的研究进展进行综述.

  20. Rare types of diabetes mellitus.

    Science.gov (United States)

    Mihai, B; Mihai, Cătălina; Cijevschi-Prelipcean, Cristina; Lăcătuşu, Cristina

    2012-01-01

    Diabetes mellitus is a heterogenous disorder characterized by chronic hyperglycemia and induced by a large number of etiopathogenic conditions. Beside type 1 and type 2 diabetes, which account for almost 90% of all cases, practitioners may encounter patients with more infrequent forms of diabetes, as those induced by mutations of a single gene, atypical immune disorders or neonatal diabetes. Monogenic diabetes is represented by genetic disorders in the structure of the beta-cell (the MODY syndromes and the mutations of mitochondrial DNA) or in the insulin's action (type A insulin resistance syndrome, Rabson-Mendenhall syndrome, leprechaunism, lipodystrophies). The rare forms of immune diabetes are determined by antibodies against insulin or insulin receptor or appear as a component of the "stiff man syndrome". Neonatal diabetes is induced by mutations in genes that control beta-cell development and function and may have a transient or permanent nature. Knowledge of the uncommon forms of diabetes mellitus enables physicians to apply the optimal treatment, to estimate the evolution of the patient and to apply a complete family screening in order to diagnose all other blood relatives as soon as possible.

  1. Mutations in the AVPR2, AVP-NPII, and AQP2 genes in Turkish patients with diabetes insipidus.

    Science.gov (United States)

    Duzenli, Duygu; Saglar, Emel; Deniz, Ferhat; Azal, Omer; Erdem, Beril; Mergen, Hatice

    2012-12-01

    The aim of this study was to identify mutations in three different genes, the arginine-vasopressin-neurophysin II (AVP-NPII) gene, the arginine-vasopressin receptor 2 (AVPR2) gene, and the vasopressin-sensitive water channel aquaporin-2 (AQP2) gene in Turkish patients affected by central diabetes insipidus or nephrogenic diabetes insipidus. This study included 15 patients from unrelated families. Prospective clinical data were collected for all patients including the patients underwent a water deprivation-desmopressin test. The coding regions of the AVPR2, AQP2, and AVP-NPII genes were amplified by polymerase chain reaction and submitted to direct sequence analysis. Of the 15 patients with diabetes insipidus referred to Gulhane Military Medical Academy, Department of Endocrinology and Metabolism, eight patients have AVPR2 mutations, five patients have AQP2 mutations and two patients have AVP-NPII mutations. Of the patients, which have AVPR2 mutations, one is compound heterozygous for AVPR2 gene. Seven of these mutations are novel. Comparison of the clinical outcomes of these mutations may facilitate in understanding the functions of AVP-NPII, AQP2, and AVPR2 genes in future studies.

  2. Mutations in the VNTR of the carboxyl-ester lipase gene (CEL) are a rare cause of monogenic diabetes

    DEFF Research Database (Denmark)

    Torsvik, Janniche; Johansson, Stefan; Johansen, Anders;

    2009-01-01

    of the VNTR, and determined the VNTR-length of each allele. When blindly testing 56 members of the two families with known single-base deletions in the CEL VNTR, the method correctly assessed the mutation carriers. Screening of 241 probands from suspected maturity-onset diabetes of the young (MODY) families...... negative for mutations in known MODY genes (95 individuals from Denmark and 146 individuals from UK) revealed no deletions in the proximal repeats of the CEL VNTR. However, we found one Danish patient with a short, novel CEL allele containing only three VNTR repeats (normal range 7-23 in healthy controls......). This allele co-segregated with diabetes or impaired glucose tolerance in the patient's family as six of seven mutation carriers were affected. We also identified individuals who had three copies of a complete CEL VNTR. In conclusion, the CEL gene is highly polymorphic, but mutations in CEL are likely...

  3. HFE Gene Mutation Among Turkish Patients with Type 2 Diabetes Mellitus

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    Erdem Akbal

    2013-12-01

    Full Text Available Purpose: Hereditary haemochromatosis (HH is a genetic disease with autosomal recessive trait. Recent studies demonstrated the importance of C282Y gene mutation in the aetiology of HH. Free iron accumulating in pancreas deteriorates insulin secretion and synthesis which can lead to insulin resistance and the development of type 2 diabetes mellitus (T2DM in patients with HH. There has been no study determining the prevalence of haemochromatosis gene (HFE mutations and HH in diabetic patients in Turkey. We planned this study in order to investigate the C282Y and H63D mutation that cause HH in T2DM. Material and Method: In this study, we included185 patients with T2DM. Patients older than thirty-five years, not taking vitamin supplementation, iron preparates and/or oral contraceptives and those without any signs of active bleeding were included while patients with any infectious, systemic or immune disease were excluded from the study. Serum transferrin saturation (TS, ferritin, iron, and total iron binding capacity levels were measured after 12 hours of fasting. Results: Ten (5.4% cases with TS of more than 45% were detected at the first evaluation. The test was repeated in those cases and 6 patients with TS of more than 45% were left according to the second measurement. H63D and C282Y gene polymorphisms were not present in these patients. Discussion: We did not find any correlation between the existence of T2DM and HFE polymorphisms. We assume that screening for HH in T2DM in our population is not needed. Turk Jem 2013; 17: 89-91

  4. WFS1 mutations in Spanish patients with diabetes mellitus and deafness.

    Science.gov (United States)

    Domènech, Enric; Gómez-Zaera, Montse; Nunes, Virginia

    2002-07-01

    Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disorder characterised by early onset diabetes mellitus and progressive optic atrophy, as well as other clinical features such as deafness, diabetes insipida, renal tract abnormalities and diverse psychiatric illnesses. A gene responsible for WS was identified in 4p16.1 (WFS1). It encodes a putative 890 amino acid transmembrane protein expressed in a wide spectrum of tissues. Recently, a new locus for WS has been located on 4q22-24, providing additional evidence for the genetic heterogeneity of this syndrome. We have studied the presence of WFS1 variants in three groups of individuals: patients with diabetes mellitus, patients with deafness and patients with both conditions. A fourth group of healthy subjects was used as control. We have identified a total of 18 nucleotide changes in the WFS1 gene: three mutations and 15 polymorphisms. Six of these changes were previously undescribed. Four of the 15 polymorphisms studied among the patients group present statistical differences in the allelic and genotypic distribution when comparing affected vs control groups.

  5. A study of familial Mediterranean Fever (MEFV) gene mutations in Egyptian children with type 1 diabetes mellitus.

    Science.gov (United States)

    Anwar, Ghada Mohammad; Fouad, Hanan M; Abd El-Hamid, Amal; Mahmoud, Faten; Musa, Noha; Lotfi, Hala; Salah, Nermine

    2015-01-01

    An association of type 1 DM and familial Mediterranean fever (FMF) has been newly reported in the medical literature. The aim of the present work was to investigate frequency of MEFV gene mutations in Egyptian children with type 1 diabetes mellitus. Forty five children with type 1 DM were screened for Mediterranean Fever (MEFV) gene mutation. Forty one healthy control subjects were included. Identification of FMF gene mutation was done based on polymerase chain reaction (PCR) and reverse hybridization. The assay covers 12 mutations in the FMF gene: E148Q - P369S - F479L - M680I (G/C) - M680I (G/A) - I692del - M694V - M694I - K695R-V726A - A744S and R761H. Among the screened diabetics, the overall frequency of MEFV gene mutations was 42.2% and among the control group it was 34.1% with no significant difference. Fourteen out of 45 diabetic children (31.1%) were heterozygous (E148Q in 7 children, A744S in 3 children, V726A in 2 children, M680I (G/C) in 1 child and P369S in1 child), while 5 children (11.1%) were compound heterozygous (M694V/M694I in 2 children, E148Q/K695R mutations in 1 child, E148Q/M694I in 1 child and E148Q/V726A in 1 child). The control group showed heterozygous mutation in 34.1% of cases (E148Q mutation in 14.6%, V726A in 12.2%, M680I (G/C) in 4.9% and M694V in 2.4%). No significant difference in mutation frequency between diabetic and non-diabetic children. We have high carrier rate of MEFV gene mutations among Egyptian population probably due to high consanguinity. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations

    DEFF Research Database (Denmark)

    Pearson, Ewan R; Flechtner, Isabelle; Njølstad, Pål R

    2006-01-01

    insulin secretion only in the presence of sulfonylureas. CONCLUSIONS: Sulfonylurea therapy is safe in the short term for patients with diabetes caused by KCNJ11 mutations and is probably more effective than insulin therapy. This pharmacogenetic response to sulfonylureas may result from the closing...

  7. Mutation Analysis of AVPR2 and AQP2 Gene in Chinese Patients with Congenital Nephrogenic Diabetes Insipidus

    Institute of Scientific and Technical Information of China (English)

    WANG Ying; LI Hong-jun; YU Zhen-xiang; BAO Yong-li; WU Yin; YU Chun-lei; MENG Xiang-ying; LI Yu-xin

    2008-01-01

    To detect mutations of the aquaporin 2 gene(AQP2) and the arginine vasopressin V2 receptor gene(AVPR2)of Chinese congenital nephrogenic diabetes insipidus, and to establish the foundation for further studying the emergence mechanism of the disease and clinical diagnosis, all the exons and part of introns of AQP2 and AVPR2 genes were amplified with intronic primers, using genomic DNA extracted from three patients with congenital nephrogenic diabetes insipidus and two mothers as template, PCR product was ligated into a T-vector and then sequenced. The result was compared with the database sequence to identify the mutable sites via a BLAST search, the incidence of every mutation was analyzed, and the putative transcription factor binding sites that maybe disturbed were analyzed by MAPPER.Mutation g.1394A>G in exon 3 of AVPR2 was detected in all the subjects, g.861C>T(S167L) in exon 2 of AVPR2 and IVS1+3G>A in intron of AQP2 were detected, respectively, in two patients, and c.836A>C in 3' untranslated region of AQP2 was detected in two patients and one mother. Four mutations were identified, g.1394A>G of AVPR2 and c.836A>C of AQP2 have high incidence in patients with nephrogenic diabetes insipidus. Detection on the two sites may become auxiliary diagnosis index of congenital nephrogenic diabetes insipidus.

  8. The Pro115Gln Missense Mutation of Peroxisome Proliferator Activated Receptor γ (PPARγ Gene in Diabetes in the Pakistani Population

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    Sumbal

    2016-05-01

    Full Text Available Background Diabetes is an alarmingly increasing public health concern. According to a World Health Organization (WHO report, diabetes is highly prevalent in almost all regions of Pakistan, with an overall prevalence of 22.04% in urban and 17.15% in rural areas. In addition to lifestyle factors, genetics plays an important part in the progression to diabetes, of which peroxisome proliferator activated receptors (PPARs, a super-family of transcriptional regulators, are considered to be very critical. Objectives The aim of the current study was to investigate the prevalence of a missense mutation Pro115Gln in the PPARγ; gene in Pakistan and search for its effects on certain serum biochemical parameters. Materials and Methods A total of 1015 subjects (490 diabetics and 525 healthy controls were genotyped by PCR-RFLP and serum profiling was performed. Results We could not detect the mutation in the study subjects, but the anthropometric and biochemical parameters were significantly different between the cases and controls. Conclusions In conclusion, as this mutation is present in a highly conserved region and any change in this region would adversely affect the protein structure and function, so the prevalence of this mutation is very low.

  9. Designing Inhibitors against HOX domain mutations of PDX-1 and studying its association in Diabetes

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    Allam Appa Rao

    2012-03-01

    Full Text Available Type 1 diabetes mellitus was formally known as IDDM, type I, or juvenile onset diabetes. Type 1 DM can occur at any age. In this study,we analyzed the involvement of HOX domain of PDX-1 protein.The homeodomain transcription factor, pancreas duodenum homeobox (PDX-1, encoded by PDX-1 gene, which is a transcriptional activator of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide, and glucose transporter type 2 and essential for pancreas development, insulin production, and glucose homeostasis.[1,13]. HOX domain has a length of 63aa and control developmental patterns and cell differentiation in vertebrates by acting positive or negative regulators[4,9,16]. Different approached had been applied to identify the mutational hot spot region of HOX domain and calculate mutational frequency of the amino acids which resides in the hotspot region. Binding site of the domain had been identified and found that THR208, GLN246 ,VAL247, ASN253 involved in interaction with ligand. Potential Inhibitors had been screened on the basis of various criteria and bioactivity score had been calculated. Energy optimization was done by applying AMBER force field and steepest descent method. Docking was performed by CCDC GOLD, Molegro, HEX, and Argus lab to find the best potent inhibitor and increase the accuracy of the docking process. Sitagliptin showed satisfactory result on both docking and bioactivity analysis. It showed a GOLD fitness score of 49.8386 and had a moldock score of -122.919 with a ligand efficiency -4.33692. Compound had a bioactivity score of 0.56 for protease inhibitor. Sitagliptin showed good binding affinity to the target, which helps to work the pancreas in proper way and to secret insulin.

  10. Impact of fetal and neonatal environment on beta cell function and development of diabetes.

    Science.gov (United States)

    Nielsen, Jens H; Haase, Tobias N; Jaksch, Caroline; Nalla, Amarnadh; Søstrup, Birgitte; Nalla, Anjana A; Larsen, Louise; Rasmussen, Morten; Dalgaard, Louise T; Gaarn, Louise W; Thams, Peter; Kofod, Hans; Billestrup, Nils

    2014-11-01

    The global epidemic of diabetes is a serious threat against health and healthcare expenses. Although genetics is important it does not explain the dramatic increase in incidence, which must involve environmental factors. Two decades ago the concept of the thrifty phenotype was introduced, stating that the intrauterine environment during pregnancy has an impact on the gene expression that may persist until adulthood and cause metabolic diseases like obesity and type 2 diabetes. As the pancreatic beta cells are crucial in the regulation of metabolism this article will describe the influence of normal pregnancy on the beta cells in both the mother and the fetus and how various conditions like diabetes, obesity, overnutrition and undernutrition during and after pregnancy may influence the ability of the offspring to adapt to changes in insulin demand later in life. The influence of environmental factors including nutrients and gut microbiota on appetite regulation, mitochondrial activity and the immune system that may affect beta cell growth and function directly and indirectly is discussed. The possible role of epigenetic changes in the transgenerational transmission of the adverse programming may be the most threatening aspect with regard to the global diabetes epidemics. Finally, some suggestions for intervention are presented. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  11. Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC.

    Science.gov (United States)

    Rubio-Cabezas, Oscar; Puri, Vishwajeet; Murano, Incoronata; Saudek, Vladimir; Semple, Robert K; Dash, Satya; Hyden, Caroline S S; Bottomley, William; Vigouroux, Corinne; Magré, Jocelyne; Raymond-Barker, Philippa; Murgatroyd, Peter R; Chawla, Anil; Skepper, Jeremy N; Chatterjee, V Krishna; Suliman, Sara; Patch, Ann-Marie; Agarwal, Anil K; Garg, Abhimanyu; Barroso, Inês; Cinti, Saverio; Czech, Michael P; Argente, Jesús; O'Rahilly, Stephen; Savage, David B

    2009-08-01

    Lipodystrophic syndromes are characterized by adipose tissue deficiency. Although rare, they are of considerable interest as they, like obesity, typically lead to ectopic lipid accumulation, dyslipidaemia and insulin resistant diabetes. In this paper we describe a female patient with partial lipodystrophy (affecting limb, femorogluteal and subcutaneous abdominal fat), white adipocytes with multiloculated lipid droplets and insulin-resistant diabetes, who was found to be homozygous for a premature truncation mutation in the lipid droplet protein cell death-inducing Dffa-like effector C (CIDEC) (E186X). The truncation disrupts the highly conserved CIDE-C domain and the mutant protein is mistargeted and fails to increase the lipid droplet size in transfected cells. In mice, Cidec deficiency also reduces fat mass and induces the formation of white adipocytes with multilocular lipid droplets, but in contrast to our patient, Cidec null mice are protected against diet-induced obesity and insulin resistance. In addition to describing a novel autosomal recessive form of familial partial lipodystrophy, these observations also suggest that CIDEC is required for unilocular lipid droplet formation and optimal energy storage in human fat.

  12. Infantile onset diabetes mellitus in developing countries-India

    Institute of Scientific and Technical Information of China (English)

    Poovazhagi; Varadarajan

    2016-01-01

    Infantile onset diabetes mellitus(IODM) is an uncommon metabolic disorder in children. Infants with onset of diabetes mellitus(DM) at age less than one year are likely to have transient or permanent neonatal DM or rarely type 1 diabetes. Diabetes with onset below 6 mo is a heterogeneous disease caused by single gene mutations. Literature on IODM is scanty in India. Nearly 83% of IODM cases present with diabetic keto acidosis at the onset. Missed diagnosis was common in infants with diabetes(67%). Potassium channel mutation with sulphonylurea responsiveness is the common type in the non-syndromic IODM and Wolcott Rallison syndrome is the common type in syndromic diabetes. Developmental delay and seizures were the associated co-morbid states. Genetic diagnosis has made a phenomenal change in the management of IODM. Switching from subcutaneous insulin to oral hypoglycemic drugs is a major clinical breakthrough in the management of certain types of monogenic diabetes. Mortality in neonatal diabetes is 32.5% during follow-up from Indian studies. This article is a review of neonatal diabetes and available literature on IODM from India.

  13. Infantile onset diabetes mellitus in developing countries - India.

    Science.gov (United States)

    Varadarajan, Poovazhagi

    2016-03-25

    Infantile onset diabetes mellitus (IODM) is an uncommon metabolic disorder in children. Infants with onset of diabetes mellitus (DM) at age less than one year are likely to have transient or permanent neonatal DM or rarely type 1 diabetes. Diabetes with onset below 6 mo is a heterogeneous disease caused by single gene mutations. Literature on IODM is scanty in India. Nearly 83% of IODM cases present with diabetic keto acidosis at the onset. Missed diagnosis was common in infants with diabetes (67%). Potassium channel mutation with sulphonylurea responsiveness is the common type in the non-syndromic IODM and Wolcott Rallison syndrome is the common type in syndromic diabetes. Developmental delay and seizures were the associated co-morbid states. Genetic diagnosis has made a phenomenal change in the management of IODM. Switching from subcutaneous insulin to oral hypoglycemic drugs is a major clinical breakthrough in the management of certain types of monogenic diabetes. Mortality in neonatal diabetes is 32.5% during follow-up from Indian studies. This article is a review of neonatal diabetes and available literature on IODM from India.

  14. Clinical features of diabetes mellitus with the mitochondrial DNA 3243 (A-G) mutation in Japanese: maternal inheritance and mitochondria-related complications.

    Science.gov (United States)

    Suzuki, Susumu; Oka, Yoshitomo; Kadowaki, Takashi; Kanatsuka, Azuma; Kuzuya, Takeshi; Kobayashi, Masashi; Sanke, Tokio; Seino, Yutaka; Nanjo, Kishio

    2003-03-01

    Diabetes mellitus with the mitochondrial DNA 3243(A-G) mutation is reported to represent 0.5-2.8% of the general diabetic population. Since the characterization of diabetes with the mutation is still incomplete, we undertook a nation-wide case-finding study of genetically defined patients using questionnaires in Japan. One hundred and thirteen Japanese diabetic patients with the mutation were registered and analyzed. The patients had a high prevalence of maternal inheritance of diabetes and deafness, short and thin stature, and showed an early middle-aged onset of diabetes and deafness. Eighty-six percent of the patients required insulin therapy due to the progressive insulin secretory defect. Glucose intolerance of the mothers was associated with an early middle-aged onset of diabetes, reduction in the insulin secretory capacity, early requirement of insulin therapy, and increases in the daily insulin dose. The heteroplasmic concentrations of the 3243 mutation in leukocytes were low and declined with aging. The patients had advanced microvascular complications, and mitochondria-related complications such as cardiomyopathy, cardiac conductance disorders, neuromuscular symptoms, neuropsychiatric disturbance, and macular pattern dystrophy. Thus, this study has revealed that: (1) diabetes mellitus with the 3243 mutation is a subtype of diabetes mellitus with mitochondria-related complications; and (2) insulin secretory ability is more severely impaired in the patients whose mothers were glucose intolerance.

  15. Current understanding of KATP channels in neonatal diseases: focus on insulin secretion disorders

    Institute of Scientific and Technical Information of China (English)

    Yi QUAN; Andrew BARSZCZYK; Zhong-ping FENG; Hong-shuo SUN

    2011-01-01

    ATP-sensitive potassium (KATP) channels are cell metabolic sensors that couple cell metabolic status to electric activity, thus regulating many cellular functions. In pancreatic beta cells, KATP channels modulate insulin secretion in response to fluctuations in plasma glucose level, and play an important role in glucose homeostasis. Recent studies show that gain-of-function and loss-of-function mutations in KATP channel subunits cause neonatal diabetes mellitus and congenital hyperinsulinism respectively. These findings lead to significant changes in the diagnosis and treatment for neonatal insulin secretion disorders. This review describes the physiological and pathophysiological functions of KATP channels in glucose homeostasis, their specific roles in neonatal diabetes mellitus and congenital hyperinsulinism, as well as future perspectives of KATP channels in neonatal diseases.

  16. Impact of Neonatal Screening and Surveillance for the TP53 R337H Mutation on Early Detection of Childhood Adrenocortical Tumors

    Science.gov (United States)

    Custódio, Gislaine; Parise, Guilherme A.; Kiesel Filho, Nilton; Komechen, Heloisa; Sabbaga, Cesar C.; Rosati, Roberto; Grisa, Leila; Parise, Ivy Z.S.; Pianovski, Mara A.D.; Fiori, Carmem M.C.M.; Ledesma, Jorge A.; Barbosa, José Renato S.; Figueiredo, Francisco R.O.; Sade, Elis R.; Ibañez, Humberto; Arram, Sohaila B.I.; Stinghen, Sérvio T.; Mengarelli, Luciano R.; Figueiredo, Mirna M.O.; Carvalho, Danilo C.; Avilla, Sylvio G.A.; Woiski, Thiago D.; Poncio, Lisiane C.; Lima, Geneci F.R.; Pontarolo, Roberto; Lalli, Enzo; Zhou, Yinmei; Zambetti, Gerard P.; Ribeiro, Raul C.; Figueiredo, Bonald C.

    2013-01-01

    Purpose The incidence of pediatric adrenocortical tumors (ACTs) is remarkably high in southern Brazil, where more than 90% of patients carry the germline TP53 mutation R337H. We assessed the impact of early detection of this mutation and of surveillance of carriers. Patients and Methods Free newborn screening was offered at all hospitals in the state of Paraná. Parents of positive newborns were tested, and relatives in the carrier line were offered screening. Positive newborns and their relatives age < 15 years were offered surveillance (periodic clinical, laboratory, and ultrasound evaluations). ACTs detected by imaging were surgically resected. Results Of 180,000 newborns offered screening, 171,649 were screened, and 461 (0.27%) were carriers. As of April 2012, ACTs had been diagnosed in 11 of these carriers but in only two neonatally screened noncarriers (P < .001); six patient cases were identified among 228 carrier relatives age < 15 years (total, 19 ACTs). Surveillance participants included 347 (49.6%) of 699 carriers. Tumors were smaller in surveillance participants (P < .001) and more advanced in nonparticipants (four with stage III disease; two deaths). Neonatally screened carriers also had neuroblastoma (n = 1), glioblastoma multiforme (n = 1), choroid plexus carcinoma (n = 2), and Burkitt lymphoma (n = 1). Cancer histories and pedigrees were obtained for 353 families that included 1,704 identified carriers. ACTs were the most frequent cancer among carrier children (n = 48). Conclusion These findings establish the prevalence of the TP53 R337H mutation in Paraná state and the penetrance of ACTs among carriers. Importantly, screening and surveillance of heterozygous carriers are effective in detecting ACTs when readily curable. PMID:23733769

  17. Ligand binding and antigenic properties of a human neonatal Fc receptor with mutation of two unpaired cysteine residues

    DEFF Research Database (Denmark)

    Andersen, Jan T; Justesen, Sune; Fleckenstein, Burkhard

    2008-01-01

    The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I-related molecule that regulates the half-life of IgG and albumin. In addition, FcRn directs the transport of IgG across both mucosal epithelium and placenta and also enhances phagocytosis in neutrophils. This new knowle...

  18. A pilot study of mitochondrial DNA point mutation A3243G in a sample of Croatian patients having type 2 diabetes mellitus associated with maternal inheritance.

    Science.gov (United States)

    Martin-Kleiner, I; Pape-Medvidović, E; Pavlić-Renar, I; Metelko, Z; Kusec, R; Gabrilovac, J; Boranić, M

    2004-12-01

    In this work, patients having type 2 diabetes mellitus and diabetic mothers were tested for the presence of mitochondrial DNA point mutation A3243G. This mutation is associated with the MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), diabetes and deafness. Twenty-two diabetic persons were screened. DNA was isolated from peripheral blood lymphocytes and from swabs of oral mucosa. The mitochondrial DNA point mutation A3243G was detected using PCR-RFLP test. The mutation was detected in oral mucosal DNA of two patients (but not from lymphocyte DNA). One patient was a man with hearing and visual impairments and proteinuria; the other was a woman having proteinuria but no hearing impairment. The mutation was not detectable in oral mucosal DNA from the control persons: 20 diabetic patients having diabetic fathers and 22 healthy, nondiabetic volunteers. The incidence of mitochondrial DNA point mutation A3243G in this study of Croatian diabetic patients is in line with data in the literature.

  19. Impact of fetal and neonatal environment on beta cell function and development of diabetes

    DEFF Research Database (Denmark)

    Nielsen, Jens H; Haase, Tobias N; Jaksch, Caroline

    2014-01-01

    that the intrauterine environment during pregnancy has an impact on the gene expression that may persist until adulthood and cause metabolic diseases like obesity and type 2 diabetes. As the pancreatic beta cells are crucial in the regulation of metabolism this article will describe the influence of normal pregnancy...... nutrients and gut microbiota on appetite regulation, mitochondrial activity and the immune system that may affect beta cell growth and function directly and indirectly is discussed. The possible role of epigenetic changes in the transgenerational transmission of the adverse programming may be the most...

  20. Neonatal McCune-Albright syndrome with survival beyond two years.

    Science.gov (United States)

    Pierce, Melinda; Scottoline, Brian

    2016-11-01

    McCune-Albright syndrome (MAS) is a rare disease resulting from a somatic, mosaic mutation of GNAS1 encoding the Gs α subunit of the G-protein coupled membrane receptor responsible for multiple hormonal signaling cascades. We present a patient with neonatal MAS who initially presented with neonatal diabetes and concern for congenital cardiac disease, and subsequently was found to have significant ACTH-independent neonatal Cushing syndrome. Her course included multi-system organ involvement, although she initially did not have obvious findings consistent with the MAS classic triad of café-au-lait macules, fibrous dysplasia, or peripheral precocious puberty. After medical and surgical treatment, she remains the only reported survivor of neonatal MAS. This clinical report alerts clinicians to the possibility of this disease in neonates with non-classical endocrine and non-endocrine manifestations of MAS, and demonstrates that this very early presentation is potentially survivable. © 2016 Wiley Periodicals, Inc.

  1. Characterization of an aquaporin-2 water channel gene mutation causing partial nephrogenic diabetes insipidus in a Mexican family: evidence of increased frequency of the mutation in the town of origin.

    NARCIS (Netherlands)

    Boccalandro, C.; Mattia, F.P. de; Guo, D.C.; Xue, L.; Orlander, P.; King, T.M.; Gupta, P.; Deen, P.M.T.; Lavis, V.R.; Milewicz, D.M.

    2004-01-01

    A Mexican family with partial congenital nephrogenic diabetes insipidus (NDI) that resulted from a mutation in the aquaporin-2 water channel (AQP2) was characterized, and the source of this rare mutation was traced to the family's town of origin in Mexico. Affected individuals with profound polyuria

  2. Characterization of an aquaporin-2 water channel gene mutation causing partial nephrogenic diabetes insipidus in a Mexican family: evidence of increased frequency of the mutation in the town of origin.

    NARCIS (Netherlands)

    Boccalandro, C.; Mattia, F.P. de; Guo, D.C.; Xue, L.; Orlander, P.; King, T.M.; Gupta, P.; Deen, P.M.T.; Lavis, V.R.; Milewicz, D.M.

    2004-01-01

    A Mexican family with partial congenital nephrogenic diabetes insipidus (NDI) that resulted from a mutation in the aquaporin-2 water channel (AQP2) was characterized, and the source of this rare mutation was traced to the family's town of origin in Mexico. Affected individuals with profound polyuria

  3. Metabolic disorders and adipose tissue insulin responsiveness in neonatally STZ-induced diabetic rats are improved by long-term melatonin treatment.

    Science.gov (United States)

    de Oliveira, Ariclécio C; Andreotti, Sandra; Farias, Talita da S M; Torres-Leal, Francisco L; de Proença, André R G; Campaña, Amanda B; de Souza, Arnaldo H; Sertié, Rogério A L; Carpinelli, Angelo R; Cipolla-Neto, José; Lima, Fábio B

    2012-05-01

    Diabetes mellitus is a product of low insulin sensibility and pancreatic β-cell insufficiency. Rats with streptozotocin-induced diabetes during the neonatal period by the fifth day of age develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, polyuria, and polydipsia aggravated by insulin resistance in adulthood. In this study, we investigated whether the effect of long-term treatment with melatonin can improve insulin resistance and other metabolic disorders in these animals. At the fourth week of age, diabetic animals started an 8-wk treatment with melatonin (1 mg/kg body weight) in the drinking water at night. Animals were then killing, and the sc, epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed, and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Blood samples were collected for biochemical assays. Melatonin treatment reduced hyperglycemia, polydipsia, and polyphagia as well as improved insulin resistance as demonstrated by constant glucose disappearance rate and homeostasis model of assessment-insulin resistance. However, melatonin treatment was unable to recover body weight deficiency, fat mass, and adipocyte size of diabetic animals. Adiponectin and fructosamine levels were completely recovered by melatonin, whereas neither plasma insulin level nor insulin secretion capacity was improved in diabetic animals. Furthermore, melatonin caused a marked delay in the sexual development, leaving genital structures smaller than those of nontreated diabetic animals. Melatonin treatment improved the responsiveness of adipocytes to insulin in diabetic animals measured by tests of glucose uptake (sc, EP, and RP), glucose oxidation, and incorporation of glucose into lipids (EP and RP), an effect that seems partially related to an increased expression of insulin receptor substrate 1, acetyl-coenzyme A carboxylase and fatty acid

  4. Monogenic diabetes mellitus in Norway

    Directory of Open Access Journals (Sweden)

    Oddmund Søvika

    2013-06-01

    Full Text Available Here, we review data on monogenic diabetes mellitus in Norway based on the Norwegian MODY Registry at Haukeland University Hospital, Bergen. This registry comprises established or suspected cases of maturity-onset diabetes of the young (MODY referred to our laboratory for genetic testing. We also present data on neonatal diabetes, another group of monogenic diabetes. To date, we have genetically diagnosed nearly 500 MODY cases in Norway. Mutations in the HNF1A gene (MODY3 were detected in about 50% of families with clinical MODY. GCK-MODY (MODY2 was the second most prevalent type, but may be underreported. We have also found mutations in the monogenic genes ABCC8, CEL, HNF1B, HNF4A, INS, KCNJ11 and NEUROD1. Based on genetic screening in the Norwegian MODY Registry and HUNT2, we estimate the number of MODY cases in Norway to be at least 2500-5000. Founder effects may determine the geographical distribution of MODY mutations in Norway. The molecular genetic testing of MODY and neonatal diabetes is mandatory for correct diagnosis and prognosis as well as choice of therapy

  5. Glucokinase diabetes in 103 families from a country-based study in the Czech Republic: geographically restricted distribution of two prevalent GCK mutations

    DEFF Research Database (Denmark)

    Pruhova, Stepanka; Dusatkova, Petra; Sumnik, Zdenek;

    2010-01-01

    Glucokinase diabetes, also called GCK-MODY or maturity-onset diabetes of the young type 2 (MODY2), is caused by heterozygous mutations in the gene encoding glucokinase (GCK). Objective: The aim of study was to investigate the current prevalence of GCK mutations in a large cohort of Czech patients...... with typical clinical appearance of GCK-MODY. In addition, we reanalyzed the negative results obtained previously by screening using the denaturing high-performance liquid chromatography (dHPLC)....

  6. Polyuria and polydipsia in a young child: diagnostic considerations and identification of novel mutation causing familial neurohypophyseal diabetes insipidus.

    Science.gov (United States)

    Stephen, Matthew D; Fenwick, Raymond G; Brosnan, Patrick G

    2012-12-01

    A 3-year 5-month-old boy was seen for second opinion regarding polydipsia and polyuria. Previously, a diagnosis of primary polydipsia was made after normal urine concentration after overnight water deprivation testing. The boy's father, paternal grandfather, and paternal aunt had diabetes insipidus treated with desmopressin acetate. Based on this young boy's symptoms, ability to concentrate urine after informal overnight water deprivation, and family history of diabetes insipidus, we performed AVP gene mutation testing. Analysis of the AVP gene revealed a novel mutation G54E that changes a normal glycine to glutamic acid, caused by a guanine to adenine change at nucleotide g.1537 (exon 2) of the AVP gene. Commonly, patients with familial neurohypophyseal diabetes insipidus (FNHDI) present within the first 6 years of life with progressively worsening polyuria and compensatory polydipsia. Since these patients have progressive loss of arginine vasopressin (AVP), they may initially respond normally to water deprivation testing and have normal pituitary findings on brain MRI. Genetic testing may be helpful in these patients, as well as preemptively diagnosing those with a mutation, thereby avoiding unnecessary surveillance of those unaffected.

  7. A dominant negative heterozygous G87R mutation in the zinc transporter, ZnT-2 (SLC30A2), results in transient neonatal zinc deficiency.

    Science.gov (United States)

    Lasry, Inbal; Seo, Young Ah; Ityel, Hadas; Shalva, Nechama; Pode-Shakked, Ben; Glaser, Fabian; Berman, Bluma; Berezovsky, Igor; Goncearenco, Alexander; Klar, Aharon; Levy, Jacob; Anikster, Yair; Kelleher, Shannon L; Assaraf, Yehuda G

    2012-08-24

    Zinc is an essential mineral, and infants are particularly vulnerable to zinc deficiency as they require large amounts of zinc for their normal growth and development. We have recently described the first loss-of-function mutation (H54R) in the zinc transporter ZnT-2 (SLC30A2) in mothers with infants harboring transient neonatal zinc deficiency (TNZD). Here we identified and characterized a novel heterozygous G87R ZnT-2 mutation in two unrelated Ashkenazi Jewish mothers with infants displaying TNZD. Transient transfection of G87R ZnT-2 resulted in endoplasmic reticulum-Golgi retention, whereas the WT transporter properly localized to intracellular secretory vesicles in HC11 and MCF-7 cells. Consequently, G87R ZnT-2 showed decreased stability compared with WT ZnT-2 as revealed by Western blot analysis. Three-dimensional homology modeling based on the crystal structure of YiiP, a close zinc transporter homologue from Escherichia coli, revealed that the basic arginine residue of the mutant G87R points toward the membrane lipid core, suggesting misfolding and possible loss-of-function. Indeed, functional assays including vesicular zinc accumulation, zinc secretion, and cytoplasmic zinc pool assessment revealed markedly impaired zinc transport in G87R ZnT-2 transfectants. Moreover, co-transfection experiments with both mutant and WT transporters revealed a dominant negative effect of G87R ZnT-2 over the WT ZnT-2; this was associated with mislocalization, decreased stability, and loss of zinc transport activity of the WT ZnT-2 due to homodimerization observed upon immunoprecipitation experiments. These findings establish that inactivating ZnT-2 mutations are an underlying basis of TNZD and provide the first evidence for the dominant inheritance of heterozygous ZnT-2 mutations via negative dominance due to homodimer formation.

  8. Mutation of mtDNA ND1 Gene in 20 Type 2 Diabetes Mellitus Patients of Gorontalonese and Javanese Ethnicity

    Directory of Open Access Journals (Sweden)

    AMIEN RAMADHAN ISHAK

    2014-12-01

    Full Text Available Mitochondrial gene mutation plays a role in the development of type two diabetes mellitus (T2DM. A point mutation in the mitochondrial gene Nicotinamide adenine dinucleotide dehydrogenase 1 (mtDNA ND1 gene mainly reported as the most common mutation related to T2DM. However, several studies have identified another SNP (single-nucleotide polymorphisms in the RNA region of mtDNA from patients from specific ethnic populations in Indonesia. Building on those findings, this study aimed to use PCR and DNA sequencing technology to identify nucleotides in RNA and ND1 fragment from 20 Gorontalonese and 20 Javanese T2DM patients, that may trigger T2DM expression. The results showed successful amplification of RNA along 294 bp for all samples. From these samples, we found two types of point mutation in Javanese patients in the G3316A and T3200C points of the rRNA and ND1 gene. In samples taken from Gorontalonese patients, no mutation were found in the RNA or ND1 region. We conclude that T2DM was triggered differently in our two populations. While genetic mutation is implicated for the 20 Javanese patients, T2DM pathogenesis in the Gorontalonese patients must be traced to other genetic, environmental, or behavioral factors.

  9. A novel AVPR2 gene mutation of X-linked congenital nephrogenic diabetes insipidus in an Asian pedigree.

    Science.gov (United States)

    Guo, Wei-Hong; Li, Qiang; Wei, Hong-Yan; Lu, Hong-Yan; Qu, Hui-Qi; Zhu, Mei

    2016-10-01

    Polyuria and polydipsia are the characteristics of congenital nephrogenic diabetes insipidus (CNDI). Approximately 90% of all patients with CNDI have X-linked hereditary disease, which is due to a mutation of the arginine vasopressin receptor 2 ( AVPR2) gene. This case report describes a 54-year-old male with polyuria and polydipsia and several male members of his pedigree who had the same symptoms. The proband was diagnosed with diabetes insipidus using a water-deprivation and arginine vasopressin stimulation test. Genomic DNA from the patient and his family members was extracted and the AVPR2 gene was sequenced. A novel missense mutation of a cytosine to guanine transition at position 972 (c.972C > G) was found, which resulted in the substitution of isoleucine for methionine at amino acid position 324 (p.I324M) in the seventh transmembrane domain of the protein. The proband's mother and daughter were heterozygous for this mutation. The novel mutation of the AVPR2 gene further broadens the phenotypic spectrum of the AVPR2 gene.

  10. A novel Dock8 gene mutation confers diabetogenic susceptibility in the LEW.1AR1/Ztm-iddm rat, an animal model of human type 1 diabetes

    NARCIS (Netherlands)

    Arndt, Tanja; Wedekind, Dirk; Jörns, Anne; Tsiavaliaris, Georgios; Cuppen, Edwin; Hedrich, Hans-Jürgen; Lenzen, Sigurd

    2015-01-01

    AIMS/HYPOTHESIS: The LEW.1AR1-iddm rat, an animal model of human type 1 diabetes, arose through a spontaneous mutation within the inbred strain LEW.1AR1. A susceptibility locus (Iddm8) on rat chromosome 1 (RNO1) has been identified previously, which is accompanied by autoimmune diabetes and the addi

  11. Avaliação da Vitalidade Fetal em Gestantes Diabéticas: Análise dos Resultados Neonatais Fetal Surveillance in Pregnancies Complicated by Diabetes: Analysis of Neonatal Outcome

    Directory of Open Access Journals (Sweden)

    Roseli Mieko Yamamoto

    2000-10-01

    Full Text Available Objetivos: estudar os testes de avaliação da vitalidade fetal em gestantes diabéticas e relacionar com os resultados neonatais. Métodos: estudamos 387 gestantes diabéticas atendidas no Setor de Vitalidade Fetal. O último exame (cardiotocografia, perfil biofísico fetal, índice de líquido amniótico e dopplervelocimetria foi relacionado com os resultados neonatais. Resultados: a população foi de 46 gestantes diabéticas tipo I (12%, 45 tipo II (12% e 296 gestacionais (76%. Entre as do tipo I, a cardiotocografia suspeita ou alterada correlacionou-se com Apgar de 1º minuto alterado (50 e 75%; pPurpose: to study the fetal well-being assessment in pregnancies complicated by diabetes, and to analyze the neonatal results. Methods: we studied 387 pregnant women with diabetes at the Fetal Surveillance Unit. The last examination (cardiotocography, fetal biophysical profile, amniotic fluid index and dopplervelocimetry was correlated with the neonatal outcome. Results: the studied population included 46 (12% type I diabetes, 45 (12% type II and 296 (76% gestational diabetes. Type I diabetes with abnormal or suspected cardiotocography was related to abnormal 1st minute Apgar (50 and 75%, p<0.05 and to the need for neonatal intensive care unit (50 and 75%, p<0.05. The abnormal biophysical profile in type II diabetic pregnancy was related to the need for neonatal intensive care (67%, p<0.05, and abnormal umbilical artery Doppler study was related to abnormal 1st minute Apgar (67%, p<0.05. Gestational diabetes with abnormal cardiotocography presented 36% abnormal 1st minute Apgar (p<0.05, 18% abnormal 5th minute Apgar (p<0.01 and 18% neonatal death (p<0.01. Abnormal amniotic fluid index was related to abnormal 5th minute Apgar (p<0.05 and need for neonatal intensive care unit (p<0.05. Gestational diabetes with abnormal umbilical artery Doppler was related (p<0.05 to: abnormal 1st and 5th minute Apgar, respectively, 25 and 8%, Need for neonatal

  12. Insulin gene mutations resulting in early-onset diabetes: marked differences in clinical presentation, metabolic status, and pathogenic effect through endoplasmic reticulum retention

    DEFF Research Database (Denmark)

    Meur, Gargi; Simon, Albane; Harun, Nasret

    2009-01-01

    the molecular mechanisms involved. RESEARCH DESIGN AND METHODS: The INS gene was sequenced in 16 French probands with unexplained MODY, 95 patients with nonautoimmune early-onset diabetes (diagnosed at ... quantitated by real-time PCR. RESULTS: A novel coding mutation, L30M, potentially affecting insulin multimerization, was identified in five diabetic individuals (diabetes onset 17-36 years) in a single family. L30M preproinsulin-GFP fluorescence largely associated with the endoplasmic reticulum (ER) in MIN6...

  13. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene.

    Directory of Open Access Journals (Sweden)

    Ewan R Pearson

    2007-04-01

    Full Text Available BACKGROUND: Macrosomia is associated with considerable neonatal and maternal morbidity. Factors that predict macrosomia are poorly understood. The increased rate of macrosomia in the offspring of pregnant women with diabetes and in congenital hyperinsulinaemia is mediated by increased foetal insulin secretion. We assessed the in utero and neonatal role of two key regulators of pancreatic insulin secretion by studying birthweight and the incidence of neonatal hypoglycaemia in patients with heterozygous mutations in the maturity-onset diabetes of the young (MODY genes HNF4A (encoding HNF-4alpha and HNF1A/TCF1 (encoding HNF-1alpha, and the effect of pancreatic deletion of Hnf4a on foetal and neonatal insulin secretion in mice. METHODS AND FINDINGS: We examined birthweight and hypoglycaemia in 108 patients from families with diabetes due to HNF4A mutations, and 134 patients from families with HNF1A mutations. Birthweight was increased by a median of 790 g in HNF4A-mutation carriers compared to non-mutation family members (p < 0.001; 56% (30/54 of HNF4A-mutation carriers were macrosomic compared with 13% (7/54 of non-mutation family members (p < 0.001. Transient hypoglycaemia was reported in 8/54 infants with heterozygous HNF4A mutations, but was reported in none of 54 non-mutation carriers (p = 0.003. There was documented hyperinsulinaemia in three cases. Birthweight and prevalence of neonatal hypoglycaemia were not increased in HNF1A-mutation carriers. Mice with pancreatic beta-cell deletion of Hnf4a had hyperinsulinaemia in utero and hyperinsulinaemic hypoglycaemia at birth. CONCLUSIONS: HNF4A mutations are associated with a considerable increase in birthweight and macrosomia, and are a novel cause of neonatal hypoglycaemia. This study establishes a key role for HNF4A in determining foetal birthweight, and uncovers an unanticipated feature of the natural history of HNF4A-deficient diabetes, with hyperinsulinaemia at birth evolving to decreased

  14. A novel SLC12A1 gene mutation associated with hyperparathyroidism, hypercalcemia, nephrogenic diabetes insipidus, and nephrocalcinosis in four patients.

    Science.gov (United States)

    Wongsaengsak, Sariya; Vidmar, Alaina P; Addala, Ananta; Kamil, Elaine S; Sequeira, Paola; Fass, Benjamin; Pitukcheewanont, Pisit

    2017-04-01

    Solute Carrier Family 12 member 1 (SLC12A1) gene encodes the sodium-potassium-chloride co-transporter (NKCC2) at the apical membrane of the thick ascending loop of Henle (TAL). Bartter's syndrome (BS) type I is a rare, autosomal recessive, renal tubular disorder associated with mutation of the SLC12A1 gene. Presenting features include: hypokalemic metabolic alkalosis, hypercalciuria and nephrocalcinosis. The many allelic variants reported present with a spectrum of phenotypes, biochemical abnormalities and clinical severities. However, to date, only two reports have described hyperparathyroidism and hypercalcemia in patients with SLC12A1 gene mutations. We describe 4 patients with 4 novel mutation variants in the SLC12A1 gene (c.735C>G, c.1137del, c.2498-2499del, and c.1833delT) presenting with variable degrees of hyperparathyroidism, hypercalcemia, hypokalemic metabolic alkalosis, nephrocalcinosis, and nephrogenic diabetes insipidus. The link between calcium and parathyroid hormone abnormalities in patients with SLC12A1 mutations is unclear; the cases described suggest an association between primary hyperparathyroidism and loss of function mutation of SLC12A1, which may result in an aberrant threshold of the calcium sensing receptor at the level of the kidney.

  15. Reassessment of the putative role of BLK-p.A71T loss-of-function mutation in MODY and type 2 diabetes

    DEFF Research Database (Denmark)

    Bonnefond, A; Yengo, L; Philippe, J;

    2013-01-01

    MODY is believed to be caused by at least 13 different genes. Five rare mutations at the BLK locus, including only one non-synonymous p.A71T variant, were reported to segregate with diabetes in three MODY families. The p.A71T mutation was shown to abolish the enhancing effect of BLK on insulin co...... content and secretion from pancreatic beta cell lines. Here, we reassessed the contribution of BLK to MODY and tested the effect of BLK-p.A71T on type 2 diabetes risk and variations in related traits.......MODY is believed to be caused by at least 13 different genes. Five rare mutations at the BLK locus, including only one non-synonymous p.A71T variant, were reported to segregate with diabetes in three MODY families. The p.A71T mutation was shown to abolish the enhancing effect of BLK on insulin...

  16. Identification of four novel mutations in the HNF-1A gene in Chinese early-onset and/or multiplex diabetes pedigrees

    Institute of Scientific and Technical Information of China (English)

    YANG Zhen; WU Song-hua; ZHENG Tai-shan; LU Hui-juan; XIANG Kun-san

    2006-01-01

    Background Mutations in the hepatocyte nuclear factor-1A gene cause the type 3 form of maturity-onset diabetes of the young (MODY3). This study was undertaken to determine mutations and sequence variations of the HNF-1A gene in Chinese with familial early-onset and/or multiplex diabetes mellitus.Methods We screened all ten exons of the HNF- 1A gene, including exon/intron junctions, by direct sequencing in 272 unrelated Chinese, including 80 healthy controls and 192 probands of early-onset and/or multiplex diabetes pedigrees.Results In addition to one silent mutation of c.864 G >C [p. G288G] in exon4 at codon 288, which had been reported previously, a total of four novel mutations including two missense mutations (c.245C>T [p.T82M] and c.390 G > T [p. Q130H]) and one frameshift mutation P353fsdelACGGGCCTGGAGC and one silent mutation c.759 G > T [p. G253G] were identified. Moreover, eleven substitutions were identified in 192 probands. Of these,three variants (-8 G>A, -128 T>G and IVS2+21 G>A) were not observed in 80 healthy controls and one of them (-8 G>A) was not reported previously and the two promoter variants co-segregated with diabetes. The genotype and allele frequencies of the other eight variants in the diabetic patients were not significantly different from those in the healthy controls. No significant relationships were observed between the eight variants of the HNF-1A gene and clinical variables (plasma glucose, insulin, C-peptide and fasting lipid profile).Conclusion The prevalence of structural mutations in the HNF-1A gene responsible for familial early-onset and/or multiplex diabetes appears to be rare among Chinese patients.

  17. Mutations in the coding regions of the hepatocyte nuclear factor 4 alpha in Iranian families with maturity onset diabetes of the young

    Directory of Open Access Journals (Sweden)

    Tavakolafshari Jalil

    2009-12-01

    Full Text Available Abstract Hepatocyte nuclear factor 4α (HNF4α is a nuclear receptor involved in glucose homeostasis and is required for normal β cell function. Mutations in the HNF4α gene are associated with maturity onset diabetes of the young type 1 (MODY1. The aim of the present study was to determine the prevalence and nature of mutations in HNF4α gene in Iranian patients with a clinical diagnosis of MODY and their family members. Twelve families including 30 patients with clinically MODY diagnosis and 21 members of their family were examined using PCR-RFLP method and in case of mutation confirmed by sequencing techniques. Fifty age and sex matched subjects with normal fasting blood sugar (FBS and Glucose tolerance test (GTT were constituted the control group and investigated in the similar pattern. Single mutation of V255M in the HNF4α gene was detected. This known mutation was found in 8 of 30 patients and 3 of 21 individuals in relatives. Fifty healthy control subjects did not show any mutation. Here, it is indicated that the prevalence of HNF4α mutation among Iranian patients with clinical MODY is considerable. This mutation was present in 26.6% of our patients, but nothing was found in control group. In the family members, 3 subjects with the age of ≤25 years old carried this mutation. Therefore, holding this mutation in this range of age could be a predisposing factor for developing diabetes in future.

  18. Antidiabetic and antihypertensive effect of Virgin Argan Oil in model of neonatal streptozotocin-induced diabetic and l-nitroarginine methylester (l-NAME) hypertensive rats.

    Science.gov (United States)

    Bellahcen, Said; Hakkou, Zineb; Ziyyat, Abderrahim; Legssyer, Abdelkhaleq; Mekhfi, Hassane; Aziz, Mohammed; Bnouham, Mohamed

    2013-07-06

    The goal of this study was to examine the effect of Virgin Argan Oil (VAO) obtained from the fruit of Argania spinosa in a model of type 2 diabetes and hypertensive rats. Neonatal diabetes was induced by a single i.p. injection of streptozotocin (90 mg/kg) 2 days after birth. To induce NO-deficient hypertension, the adult diabetic animals were treated with l-nitroarginine methylester (l-NAME) (30 mg/kg/day) given orally for 21 days. Following treatment with VAO (21 days), the hyperglycemia decreased to 1.3 ± 0.07 g/l compared with 1.92 ± 0.09 g/l (p < 0.01) in the untreated diabetic-hypertensive rats. The simultaneous administration of VAO with l-NAME prevented the increase in blood pressure during the 3 weeks of treatment. Blood pressure remained constant at 131 ± 1 mm Hg after 21 days - vs 157 ± 0.64 mm Hg in untreated animals (p < 0.001). The treatment with VAO to diabetic-hypertensive rats caused a significant increase of hepatic glycogen levels (13.3 ± 1.8 vs 6.34 ± 0.75 mg/g tissue in untreated diabetic-hypertensive control group; p < 0.01). In conclusion, the overall findings indicate that VAO possesses antidiabetic and antihypertensive activity in n-stz/l-NAME rats. This effect may be related to its high content of tocopherols, phenolic compounds, and unsaturated fatty acids.

  19. Identification and analysis of novel R308K mutation in glucokinase of type 2 diabetic patient and its kinetic correlation.

    Science.gov (United States)

    Yellapu, Nanda Kumar; Valasani, Koteswara Rao; Pasupuleti, Santhosh Kumar; Gopal, Sowjenya; Potukuchi Venkata Gurunadha Krishna, Sarma; Matcha, Bhaskar

    2014-01-01

    Glucokinase (GK) plays a critical role in glucose homeostasis and the mutations in GK gene result in pathogenic complications known as Maturity Onset Diabetes of the Young 2, an autosomal dominant form of diabetic condition. In the present study, GK was purified from human liver tissue and the pure enzyme showed single band in SDS-PAGE with a molecular weight of 50 kDa. The kinetics of pure GK showed enzyme activity of 0.423±0.02 µM glucose-6-phosphate (G6P)/mL/Min and Km value of 6.66±0.02 µM. These values were compared in the liver biopsy of a clinically proven type 2 diabetic patient, where GK kinetics showed decreased enzyme activity of 0.16±0.025 µM G6P/mL/Min and increased Km of 23±0.9 µM, indicating the hyperglycemic condition in the patient. The genetic analysis of 10th exon of GK gene from this patient showed a R308K mutation. To substantiate these results, comparative molecular dynamics and docking studies were carried out where a higher docking score (-10.218 kcal/mol) was observed in the mutated GK than wild-type GK structure (-12.593 kcal/mol) indicating affinity variations for glucose. During the simulation process, glucose was expelled out from the mutant conformation but not from wild-type GK, making glucose unavailable for phosphorylation. Therefore, these results conclusively explain hyperglycemic condition in this patient. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  20. 格列本脲治疗新生儿糖尿病2例报道及文献分析%Follow-up Analysis of 2 Cases of Neonatal Diabetes Mellitus Treated with Glibenclamide

    Institute of Scientific and Technical Information of China (English)

    刘芳; 卫海燕; 陈永兴

    2012-01-01

    目的:总结新生儿糖尿病的临床特点,为临床提供诊疗经验.方法:对郑州市儿童医院内分泌科2010年2月~5月诊治的2例新生儿糖尿病患儿的临床资料进行分析、总结,并复习相关文献.结果:2例新生儿糖尿病患儿病初给予胰岛素治疗效果不佳,改为格列本脲后血糖控制良好,1例患儿治疗5个月停药,1例患儿持续应用小剂量格列本脲维持血糖控制良好.结论:新生儿糖尿病当应用胰岛素治疗效果不佳时,可能为KCNJ11基因突变所致,若无条件对新生儿糖尿病患儿进行基因检测,可试验性应用格列本脲治疗.%Objective: To provide experiences of diagnosis and treatment for clinicians through summarizing the clinical characteristics of neonatal diabetes mellitus. Methods; Two cases in department of endocrinology of Zhengzhou Children' s Hospital were recruited from Feb. 2010 to May 2010. Clinical data of them were analyzed and summarized. Related documents were also studied. Results: Because of the poor results of insulin treatment, two cases were switched to glibenclamide therapy and serum glucose was well controlled. One case has been withdrawal after 5 months; another continued to take low-dose glibenclamide and serum glucose was well controlled. Conclusions: It could be caused by the mutation of gene KCNJ11 when insulin treatment for neonatal diabetes mellitus was not very effective. Experimental glibenclamide treatment could be adopted when gene detection could not be performed.

  1. The AQP2 mutation V71M causes nephrogenic diabetes insipidus in humans but does not impair the function of a bacterial homolog.

    Science.gov (United States)

    Klein, Noreen; Kümmerer, Nadine; Hobernik, Dominika; Schneider, Dirk

    2015-01-01

    Several point mutations have been identified in human aquaporins, but their effects on the function of the respective aquaporins are mostly enigmatic. We analyzed the impact of the aquaporin 2 mutation V71M, which causes nephrogenic diabetes insipidus in humans, on aquaporin structure and activity, using the bacterial aquaglyceroporin GlpF as a model. Importantly, the sequence and structure around the V71M mutation is highly conserved between aquaporin 2 and GlpF. The V71M mutation neither impairs substrate flux nor oligomerization of the aquaglyceroporin. Therefore, the human aquaporin 2 mutant V71M is most likely active, but cellular trafficking is probably impaired.

  2. A novel splice site mutation of the arginine vasopressin-neurophysin II gene identified in a kindred with autosomal dominant familial neurohypophyseal diabetes insipidus.

    Science.gov (United States)

    Tae, Hyun-Jung; Baek, Ki-Hyun; Shim, Sun-Mi; Yoo, Soon-Jib; Kang, Moo-Il; Cha, Bong-Yun; Lee, Kwang-Woo; Son, Ho-Young; Kang, Sung-Koo

    2005-01-01

    Autosomal dominant familial neurohypophyseal diabetes insipidus is an inherited deficiency of arginine vasopressin (AVP), and this is caused by mutations in the AVP-neurophysin II (AVP-NP II) gene. Most of these mutations have been located in the signal peptide or in the NP II moiety. In the present study, we have analyzed the AVP-NP II gene in a Korean family. Clinical and genetic studies were performed on three members of the family, and on a normal healthy unrelated individual. The diagnosis of neurohypophyseal diabetes insipidus was done by performing a fluid deprivation test and a vasopressin challenge. For genetic analysis, the genomic DNA was extracted and the AVP-NP II gene was amplified by polymerase chain reaction (PCR). Clinical assessment of the affected individuals confirmed the diagnosis of neurohypophyseal diabetes insipidus. Genetic analysis of the AVP-NP II gene revealed a novel deletion mutation of a single nucleotide (guanine) within the splice acceptor site of intron 2 (IVS2 +1 delG). The affected individuals were heterozygous for this mutation. We also demonstrated through RT-PCR analysis of the mutant gene that this mutation resulted in the retention of intron 2 during pre-mRNA splicing. We concluded that a novel splicing mutation in the AVP-NP II gene causes neurohypophyseal diabetes insipidus in this family.

  3. A novel mutation MT-COIII m.9267G>C and MT-COI m.5913G>A mutation in mitochondrial genes in a Tunisian family with maternally inherited diabetes and deafness (MIDD) associated with severe nephropathy.

    Science.gov (United States)

    Tabebi, Mouna; Mkaouar-Rebai, Emna; Mnif, Mouna; Kallabi, Fakhri; Ben Mahmoud, Afif; Ben Saad, Wafa; Charfi, Nadia; Keskes-Ammar, Leila; Kamoun, Hassen; Abid, Mohamed; Fakhfakh, Faiza

    2015-04-10

    Mitochondrial diabetes (MD) is a heterogeneous disorder characterized by a chronic hyperglycemia, maternal transmission and its association with a bilateral hearing impairment. Several studies reported mutations in mitochondrial genes as potentially pathogenic for diabetes, since mitochondrial oxidative phosphorylation plays an important role in glucose-stimulated insulin secretion from beta cells. In the present report, we studied a Tunisian family with mitochondrial diabetes (MD) and deafness associated with nephropathy. The mutational analysis screening revealed the presence of a novel heteroplasmic mutation m.9276G>C in the mitochondrial COIII gene, detected in mtDNA extracted from leukocytes of a mother and her two daughters indicating that this mutation is maternally transmitted and suggest its implication in the observed phenotype. Bioinformatic tools showed that m.9267G>C mutation (p.A21P) is « deleterious » and it can modify the function and the stability of the MT-COIII protein by affecting the assembly of mitochondrial COX subunits and the translocation of protons then reducing the activity of the respective OXPHOS complexes of ATP synthesis. The nonsynonymous mutation (p.A21P) has not been reported before, it is the first mutation described in the COXIII gene which is related to insulin dependent mitochondrial diabetes and deafness and could be specific to the Tunisian population. The m.9267G>C mutation was present with a nonsynonymous inherited mitochondrial homoplasmic variation MT-COI m.5913 G>A (D4N) responsible of high blood pressure, a clinical feature detected in all explored patients.

  4. Ethnic-specific splicing mutation of the carnitine-acylcarnitine translocase gene in a Chinese neonate presenting with sudden unexpected death

    Institute of Scientific and Technical Information of China (English)

    林青云; 赖志刚; 周镇邦; 汤瑞芳; 袁月冰; 麦婉芳; 陈恩和

    2003-01-01

    Carnitine-acylcarnitine translocase (CACT) deficiency (OMIM 212138) is an autosomal recessive disease caused by mutations of the SLC25A20 gene [solute carrier family 25 (carnitine/acylcarnitine translocase), member 20]. The gene has an open reading frame of 903 bp,1 mapped to chromosome 3p21.31 by in situ hybridization,2 and encodes a protein having three repeated homologous domains, each about 100 amino acids in length-a characteristic feature of mitochondrial transport proteins.3,4 CACT is essential in long-chain fatty acid oxidation because CACT is located in the inner side of the inner mitochondrial membrane, shuttling long-chain acylcarnitines in the intermembranous space against carnitine in the mitochondrial matrix. The first patient with CACT deficiency reported in the United States,5 and the first patient reported in the United Kingdom6 are both of mixed ethnicity with one of the parents being Chinese. Intriguingly, there is no single case of CACT deficiency reported in Chinese populations, suggesting that this disease may be underdiagnosed in Chinese populations. In this study, we have confirmed that CACT deficiency can be a cause of sudden neonatal death in Chinese.

  5. Identification and functional characterisation of novel glucokinase mutations causing maturity-onset diabetes of the young in Slovakia.

    Directory of Open Access Journals (Sweden)

    Lucia Valentínová

    Full Text Available Heterozygous glucokinase (GCK mutations cause a subtype of maturity-onset diabetes of the young (GCK-MODY. Over 600 GCK mutations have been reported of which ∼65% are missense. In many cases co-segregation has not been established and despite the importance of functional studies in ascribing pathogenicity for missense variants these have only been performed for C, c.1113-1114delGC were novel. Parental DNA was available for 22 probands (covering 14/22 mutations and co-segregation established in all cases. Bioinformatic analysis predicted all missense mutations to be damaging. Nine (I110N, V200A, N204D, G223S, G258R, F419S, V244G, L315H, I436N mutations were functionally evaluated. Basic kinetic analysis explained pathogenicity for 7 mutants which showed reduced glucokinase activity with relative activity indices (RAI between 0.6 to <0.001 compared to wild-type GCK (1.0. For the remaining 2 mutants additional molecular mechanisms were investigated. Differences in glucokinase regulatory protein (GKRP -mediated-inhibition of GCK were observed for both L315H & I436N when compared to wild type (IC(50 14.6±0.1 mM & 20.3±1.6 mM vs.13.3±0.1 mM respectively [p<0.03]. Protein instability as assessed by thermal lability studies demonstrated that both L315H and I436N show marked thermal instability compared to wild-type GCK (RAI at 55°C 8.8±0.8% & 3.1±0.4% vs. 42.5±3.9% respectively [p<0.001]. The minimum prevalence of GCK-MODY amongst Slovakian patients with diabetes was 0.03%. In conclusion, we have identified 22 GCK mutations in 36 Slovakian probands and demonstrate that combining family, bioinformatic and functional studies can aid the interpretation of variants identified by molecular diagnostic screening.

  6. A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2.

    Science.gov (United States)

    Hinrichs, Gitte R; Hansen, Louise H; Nielsen, Maria R; Fagerberg, Christina; Dieperink, Hans; Rittig, Søren; Jensen, Boye L

    2016-04-01

    Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome of inappropriate antidiuresis or congenital X-linked nephrogenic diabetes insipidus. We present a novel mutation in codon 137 within AVPR2 with substitution of glycine for arginine in male dizygotic twins. Nephrogenic diabetes insipidus was demonstrated by water deprivation test and resistance to vasopressin administration. While a similar urine exosome release rate was shown between probands and controls by western blotting for the marker ALIX, there was a selective decrease in exosome aquaporin-2 versus aquaporin-1 protein in probands compared to controls.

  7. Novel deletion and a new missense mutation (Glu 217 Lys) at the catalytic site in two adenosine deaminase alleles of a patient with neonatal onset adenosine deaminase severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Hirschhorn, R.; Nicknam, M.N.; Eng, F.; Yang, D.R.; Borkowsky, W. (New York Univ. Medical School of Medicine, NY (United States))

    1992-11-01

    Mutations at the adenosine deaminase (ADA) locus result in a spectrum of disorders, encompassing a fulminant neonatal onset severe combined immunodeficiency (SCID) and childhood onset immunodeficiency, as well as apparently normal immune function. The extent of accumulation of the toxic metabolite, deoxyATP, correlates directly with severity of disease. The authors have now determined the mutations on both alleles of a child with fulminant, neonatal onset ADA SCID and accumulation of extremely high concentrations of deoxyATP. The genotype was consistent with the severely affected phenotype. One allele carried a large deletion that arose by non-homologous recombination and included the first five exons and promoter region. The second allele carried a missense mutation (G[sup 649]A) resulting in replacement of Glu[sup 217], an amino acid involved in the catalytic site, by Lys and predicting a major alteration in charge. Expression of the mutant cDNA on Cos cells confirmed that the mutation abolished enzyme activity. The authors have previously reported that a missense mutation at the preceding codon is similarly associated with neonatal onset ADA SCID and accumulation of extremely high deoxyATP. These findings suggest that genotype-phenotype correlations may be apparent for ADA SCID, despite the role that random variation in exposure to environmental pathogens may play in the initial phenotype. Such genotype-phenotype correlations may be important to consider in evaluating results of ongoing trials of [open quotes]gene[close quotes] and enzyme replacement therapy. 50 refs., 5 figs., 2 tabs.

  8. A three-step programmed method for the identification of causative gene mutations of maturity onset diabetes of the young (MODY).

    Science.gov (United States)

    Li, Qian; Cao, Xi; Qiu, Hai-Yan; Lu, Jing; Gao, Rui; Liu, Chao; Yuan, Ming-Xia; Yang, Guang-Ran; Yang, Jin-Kui

    2016-08-22

    To establish a three-step programmed method to find gene mutations related to maturity onset diabetes of the young (MODY). Target region capture and next-generation sequencing (NGS) were performed using customized oligonucleotide probes designed to capture suspected genes for MODY in 11 probands with clinically diagnosed MODY. The suspected associations of certain genes with MODY were then confirmed by Sanger sequencing in the probands and their family members. Finally, to validate variants of one of the genes of interest (glucokinase, GCK) as pathogenic mutations, protein function editing by the variant genes was assessed. In the target region capture and NGS phase, a total of nine variants of seven genes (GCK, WFS1, SLC19A2, SH2B1, SERPINB4, RFX6, and GATA6) were identified in eight probands. Two heterozygous GCK mutations located on the same allele (p.Leu77Arg and p.Val101Met) were identified in a MODY family. Sanger sequencing was used to confirm the variants identified by NGS to be present in probands and their diabetic family members, but not in non-diabetic family members. Finally, enzyme kinetic and thermal stability analyses revealed that the p.Leu77Arg mutation or the p.Leu77Arg mutation in combination with the p.Val101Met mutation inactivates GCK function and stability, while mutation of p.Val101Met alone does not. The p.Leu77Arg but not p.Val101Met GCK mutation is therefore considered a pathogenic mutation associated with MODY. Genetic screening coupled with gene-editing protein function testing is an effective and reliable method by which causative gene mutations of MODY can be identified.

  9. Clinical and molecular analysis of a Chinese family with autosomal dominant neurohypophyseal diabetes insipidus associated with a novel missense mutation in the vasopressin-neurophysin II gene.

    Science.gov (United States)

    Luo, Yongfeng; Wang, Binbin; Qiu, Yu; Zhang, Chuan; Jin, Chengluo; Zhao, Yakun; Zhu, Qingguo; Ma, Xu

    2012-08-01

    The objective of this study is to identify the genetic defects in a Chinese family with autosomal dominant familial neurohypophyseal diabetes insipidus. Complete physical examination, fluid deprivation, and DDAVP tests were performed in three affected and three healthy members of the family. Genomic DNA was extracted from leukocytes of venous blood of these individuals for polymerase chain reaction amplification and direct sequencing of all three coding exons of arginine vasopressin-neurophysin II (AVP-NPII) gene. Seven members of this family were suspected to have symptomatic vasopressin-deficient diabetes insipidus. The water deprivation test in all the patients confirmed the diagnosis of vasopressin-deficient diabetes insipidus, with the pedigree demonstrating an autosomal dominant inheritance. Direct sequence analysis revealed a novel mutation (c.193T>A) and a synonymous mutation (c.192C>A) in the AVP-NPII gene. The missense mutation resulted in the substitution of cysteine by serine at a highly conserved codon 65 of exon 2 of the AVP-NPII gene in all affected individuals, but not in unaffected members. We concluded that a novel missense mutation in the AVP-NPII gene caused neurohypophyseal diabetes insipidus in this family, due to impaired neurophysin function as a carrier protein for AVP. The Cys65 is essential for NPII in the formation of a salt bridge with AVP. Presence of this mutation suggests that the portion of the neurophysin peptide encoded by this sequence is important for the normal expression of vasopressin.

  10. Maternal and Neonatal Circulating Markers of Metabolic and Cardiovascular Risk in the Metformin in Gestational Diabetes (MiG) Trial

    OpenAIRE

    2013-01-01

    OBJECTIVE This study was designed to compare glucose, lipids, and C-reactive protein (CRP) in women with gestational diabetes mellitus treated with metformin or insulin and in cord plasma of their offspring and to examine how these markers relate to infant size at birth. RESEARCH DESIGN AND METHODS Women with gestational diabetes mellitus were randomly assigned to metformin or insulin in the Metformin in Gestational Diabetes trial. Fasting maternal plasma glucose, lipids, and CRP were measure...

  11. GCK gene mutations are a common cause of childhood‐onset MODY (maturity‐onset diabetes of the young) in Turkey

    OpenAIRE

    Haliloglu, Belma; Hysenaj, Gerald; Atay, Zeynep; Guran, Tulay; Abalı, Saygın; Turan, Serap; Bereket, Abdullah; Ellard, Sian

    2016-01-01

    Summary Objective Inactivating heterozygous mutations in the GCK gene are a common cause of MODY and result in mild fasting hyperglycaemia, which does not require treatment. We aimed to identify the frequency, clinical and molecular features of GCK mutations in a Turkish paediatric cohort. Design and Patients Fifty‐four unrelated probands were selected based on the following criteria: age of diagnosis ≤17 years, family history of diabetes in at least two generations, anti‐GAD/ICA negative, BM...

  12. Metformin treatment of diabetes mellitus increases the risk for pancreatitis in patients bearing the CFTR-mutation S573C.

    Science.gov (United States)

    Kongsuphol, Patthara; Cassidy, Diane; Romeiras, Francisco; Schreiber, Rainer; Mehta, Anil; Kunzelmann, Karl

    2010-01-01

    Metformin use in diabetes can cause acidosis and might be linked to pancreatitis. Here, we mechanistically focus on this relationship via a point mutation in the cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7). CFTR is an ATP-hydrolyzing, cAMP/PKA-activated anion channel regulating pancreatic bicarbonate/chloride secretion across duct-facing apical membranes in epithelia. CFTR has two nucleotide binding domains (NBD1/2) which clamp two ATP molecules across their opposed, inverted interfacial surfaces which generates anion-conductance after ATP hydrolysis. Notably, CFTR mutations not causal for classical cystic fibrosis segregate with unexplained pancreatitis and one of these lies in NBD1 near its ATP-clamp (S573C; close to the Walker B aspartate D572). We recently showed that after raising [cAMP], wt-CFTR chloride-conductance, when expressed in Xenopus oocytes, remains elevated despite the presence of metformin. Yet here, we find that S573C-CFTR manifests a metformin-inhibitable whole cell chloride-conductance after cAMP elevation. In the absence of metformin, cAMP-activated S573C-CFTR also displays a reduced anion-conductance relative to wt-CFTR. Furthermore, intra-oocyte acidification inhibited wt-CFTR and abolished S573C-CFTR conductance. We conclude that defective S573C-CFTR remains both poorly conducting and inhibited by metformin and intracellular acidosis. This might explain the propensity to pancreatitis with this rare CF mutation.

  13. Prevalence and clinical characterization of Japanese diabetes mellitus with an A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA{sup Leu (UUR)} gene

    Energy Technology Data Exchange (ETDEWEB)

    Odawara, Masato; Sasaki, Kayoko; Yamashita, Kamejiro [Univ. of Tsukuba (Japan)

    1995-04-01

    An A-to-G mutation at nucleotide position 3243 of the mitochondrial genome has been associated with insulin-dependent diabetes mellitus (IDDM) and with noninsulin-dependent diabetes mellitus (NIDDM) with deafness. We investigated the prevalence of this mutation in Japanese patients with IDDM, NIDDM, and impaired glucose tolerance (IGT) and in nondiabetic control individuals, and we identified it in 3 of 300 patients with NIDDM or IGT (1.0%). None of these individuals had significant sensorineural hearing loss. None of the 94 IDDM or the 115 nondiabetic control subjects was positive for this mutation. Oral glucose tolerance test revealed that a 57-yr-old male with this mutation was rather hyperinsulinemic in the fasting state. The insulin secretion in this patient decreased with age; he did not complain of any hearing disorder, although audiometry revealed a slight elevation of hearing threshold at high frequencies. In conclusion, we found that a mitochondrial gene mutation at nucleotide position 3243 was present in about 1% of NIDDM patients including those patients with IGT. The subtype of diabetes mellitus with this mutation may have a clinical profile similar to that found in patients with NIDDM commonly seen in outpatient clinics. 25 refs., 2 figs., 1 tab.

  14. Complex phenotype linked to a mutation in exon 11 of the lamin A/C gene: Hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes.

    Science.gov (United States)

    Francisco, Ana Rita G; Santos Gonçalves, Inês; Veiga, Fátima; Mendes Pedro, Mónica; Pinto, Fausto J; Brito, Dulce

    2017-09-01

    The lamin A/C (LMNA) gene encodes lamins A and C, which have an important role in nuclear cohesion and chromatin organization. Mutations in this gene usually lead to the so-called laminopathies, the primary cardiac manifestations of which are dilated cardiomyopathy and intracardiac conduction defects. Some mutations, associated with lipodystrophy but not cardiomyopathy, have been linked to metabolic abnormalities such as diabetes and severe dyslipidemia. Herein we describe a new phenotype associated with a mutation in exon 11 of the LMNA gene: hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes. A 64-year-old woman with hypertrophic cardiomyopathy and a point mutation in exon 11 of the LMNA gene (c.1718C>T, Ser573Leu) presented with severe symptomatic ventricular hypertrophy and left ventricular outflow tract obstruction. She underwent septal alcohol ablation, followed by Morrow myectomy. The patient was also diagnosed with severe dyslipidemia, diabetes and obesity, and fulfilled diagnostic criteria for metabolic syndrome. No other characteristics of LMNA mutation-related phenotypes were identified. The development of type III atrioventricular block with no apparent cause, and mildly depressed systolic function, prompted referral for cardiac resynchronization therapy. In conclusion, the association between LMNA mutations and different phenotypes is complex and not fully understood, and can present with a broad spectrum of severity. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. The 1:3 Matched Case-Control Study of Genetic Mutations of Gestational Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    Ying Sun; Jian-hua Wang; Xiu-ying Qi

    2005-01-01

    @@ Gestational diabetes mellitus (GDM) is defined as a glucose intolerance of varying degree with onset of first recognition during pregnancy. Although glucose tolerance of GDM patients usually return to normal after delivery, 30%-50%of women with a previous history of GDM subsequently develop diabetes within a decade of the original diagnosis.The pathogenesis of GDM remains unclear. A number of candidate genes that influence carbohydrate metabolism,such as glucokinase (GCK), insulin receptor (INSR), and phosphoglucomutase, have been investigated.

  16. High risk of neonatal complications in children of mothers with gestational diabetes mellitus in their first pregnancy

    DEFF Research Database (Denmark)

    Wielandt, Hanne; Schønemann-Rigel, Helena; Blunck, Charlotte H.;

    2015-01-01

    intensive care unit. Conclusion: The present study supports the notion of high-risk pregnancy among GDM patients. Compared with nulliparous in general, the offspring were more likely to be delivered by emergency CS. Despite the prophylactic pro­ced­ures, one in six had neonatal hypoglycaemia....

  17. Homozygosity for a severe novel medium-chain acyl-CoA dehydrogenase (MCAD) mutation IVS3-1G > C that leads to introduction of a premature termination codon by complete missplicing of the MCAD mRNA and is associated with phenotypic diversity ranging from sudden neonatal death to asymptomatic

    DEFF Research Database (Denmark)

    Korman, Stanley H; Gutman, Alisa; Brooks, Rivka

    2004-01-01

    and the first reported splice mutation in the MCAD gene that has been functionally characterized. The association of homozygosity for a null mutation with lethal neonatal presentation in the index patient and presumably the previous infant suggested a genotype/phenotype correlation. However, a 6-year...

  18. Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin.

    Science.gov (United States)

    Russo, G T; Giandalia, A; Romeo, E L; Scarcella, C; Gambadoro, N; Zingale, R; Forte, F; Perdichizzi, G; Alibrandi, A; Cucinotta, D

    2016-03-01

    Hyperhomocysteinemia and vitamin B12 deficiency may be involved in the development of diabetic peripheral neuropathy (DPN). Metformin therapy may reduce vitamin B12 plasma levels, thus contributing to DPN. The purposes of this cross-sectional study were to assess (1) the potential associations of DPN with serum levels of homocysteine (tHcy), B-vitamins, and/or the common methylenetetrahydrofolate reductase (MTHFR) C677T mutation; (2) the influence of chronic treatment with metformin on tHcy and B-vitamins concentrations and, finally, (3) to evaluate whether, by this influence, metformin is a risk factor for DPN in a group of type 2 diabetic outpatients. Our data showed that fasting tHcy, folate, and vitamin B12 levels and the MTHFR C677T genotype distribution were comparable between subjects with (n = 79, 30 %) and without DPN (n = 184, 70 %). Metformin-treated subjects (n = 124, 47 %) showed significantly lower levels of vitamin B12 (P vitamin B12 level reduction, but not with DPN.

  19. Diabetes (db/db mutation-induced endometrial epithelial lipoapoptosis: Ultrastructural and cytochemical analysis of reproductive tract atrophy

    Directory of Open Access Journals (Sweden)

    Garris David R

    2005-04-01

    Full Text Available Abstract Background The diabetes (db/db mutation in C57BL/KsJ mice promotes a progressive cytolipidemia within the endometrial epithelial (EE layer of the female reproductive tract which results in premature cellular and organ atrophy. The current studies focus on the ultrastructural and cytochemical changes which promote nuclear apoptosis and cytostructural disruption following the expression of endometrial hypercytolipidemia which promotes diabetes-associated organoinvolution and manifest infertility. Methods Control (normal:+/+ and diabetes (db/db genotype groups were prepared for high resolution light microscopic analysis of cytolipidemia and nuclear apoptosis (TUNEL-labeled 3'-DNA fragmentation indices and compared to the transmission electron (TEM microscopic analysis of endometrial tissue samples collected from 8–16 week-old groups. Results Compared to controls, db/db mutation expression induced a dramatic increase in EE cytolipid vacuole volume and density within the epithelial endometrial layer. TEM analysis revealed that cytolipid vacuole accumulations initially aggregated at the baso-polar regions of UEE cells in response to the systemic hyperglycemic/hypertriglyceridemic conditions which characterized the (db/db groups. Progressive cytoplasmic movement of the lipid pools into perinuclear compartments of affected EE cells induced nuclear isolation from organelles that were displaced towards peripheral cytoplasmic compartments. Cytochemical analysis of lipid vacuole accumulations indicated attraction towards, and incorporation within, the nuclear envelope of hyperlipidemic cells. Co-localization of nuclear apoptotic 3'-DNA fragments within identified hyperlipidemic EE cells was coincident with the cytochemical and ultrastructural identification of lipid penetration through the nuclear envelope in db/db mutants. Conclusion These results are the first cytochemical indication that the metabolic disturbances in db/db mutants which

  20. Increased Proportion of Hematopoietic Stem and Progenitor Cell Population in Cord Blood of Neonates Born to Mothers with Gestational Diabetes Mellitus

    Science.gov (United States)

    Hadarits, Orsolya; Zóka, András; Barna, Gábor; Al-Aissa, Zahra; Rosta, Klára; Rigó, János; Kautzky-Willer, Alexandra; Somogyi, Anikó

    2016-01-01

    We assessed the hematopoietic stem and progenitor cell (HSPC) population in the cord blood of neonates born to mothers with gestational diabetes mellitus (GDM) in a hypothesis generating pilot study, due to that, neonatal polycythemia may be the consequence of GDM pregnancy. Forty-five pregnant women with GDM (last trimester mean HbA1C = 33.9 mmol/mol) and 42 (nondiabetic) control pregnant women were enrolled after their routine 75 g oral glucose tolerance test (OGTT) between the 24th and 28th gestational week (with expected differences in their mean routine clinical characteristics: plasma glucose at OGTT: 0′ = 5.07 vs. 4.62 mM, 120′ = 8.9 vs. 5.76 mM, age = 35.07 vs. 31.66 years, prepregnancy body mass index = 27.9 vs. 23.9 kg/m2, GDM vs. control, respectively) on a voluntary basis after signing the informed consent. EDTA-treated cord blood samples were analyzed by flow cytometry and the software Kaluza1.2 using CD45 and CD34-specific fluorescent antibodies to identify the HSPC population (CD34+ cells within the CD45dim blast gate). The proportion of CD34+CD45dim HSPCs among the nucleated cells was significantly (P < 0.05, statistical power = 60.8%) higher in the cord blood samples of neonates born to mothers with GDM (median 0.38%) compared to neonates born to nondiabetic mothers (median 0.32%) and according to treatment types (P < 0.05) median: control 0.32%, GDM-diet only 0.37%, GDM-on insulin 0.45%; control versus GDM on insulin (P < 0.05). The increased proportion of circulating CD34+CD45dim cells in the cord blood may possibly be related to altered fetal stem cell mobilization in GDM pregnancy, yet these results should be interpreted only as preliminary due to the small sample sizes. PMID:26494027

  1. Scanning and analysis of the KATP channel mutations in 12 cases of infancy onset type 1 diabetes mellitus%婴儿期起病的1型糖尿病患儿12例ATP敏感性钾通道基因突变分析

    Institute of Scientific and Technical Information of China (English)

    任力; 杨文利; 闫洁; 吴玉筠; 桑艳梅; 朱逞; 倪桂臣

    2016-01-01

    Objective To screen the mutation of KATP channel mutations in Chinese pedigrees with infantile onset type 1 diabetes mellitus (T1DM) and neonatal diabetes mellitus.Methods A cohort of 12 children of infant onset T1DM and neonatal diabetes mellitus admitted into Beijing Children's Hospital between March 2004 and June 2013 were selected.PCR amplification and direct sequencing were used to analyze the 39 exons of ABCC8 gene and one exon of KCNJ11.And the mutational sites of the parents of the probands was sequenced in order to identify the inheritance.Results Analysis revealed ABCC8 mutation in 25% (3/12 cases) of the patients,a case of transient neonatal diabetes (TNDM),a case of permanent neonatal diabetes mellitus (PNDM) and a case of infant onset T1DM.All positive patients showed a known heterozygosis mutation in the ABCC8 gene(R1182Q,c.3545G > A,D209E,c.627C > G,E208K c.622G > A).The residue R1182Q,which was located at a position involved in joining transmembrane domain 2 to nucleotide binding domain 2,the mutations E208K and D209E were located in the intracellular region that links the transmembrane domain with the gatekeeper module.All the three mutations were located throughout the cytoplasm part of SUR1 protein.The TNDM successfully transferred from insulin to oral sulfonylureas therapy.Conclusions There is a complex genetic pathogenesis in neonatal and infant-onset diabetes.The KATP channel activating mutations is one of the main causes of neonatal diabetes mellitus and may cause T1DM in infants in China.Oral Glibenclamide therapy seems highly effective for some patients with the KATP channel activating mutations.%目的 了解ATP敏感性钾通道(KATP)基因突变致中国婴儿1型糖尿病(T1DM)及新生儿糖尿病的发病情况及致病机制.方法 选取北京儿童医院2004年3月至2013年6月住院的婴儿T1DM及新生儿糖尿病患儿12例为研究对象,应用PCR扩增和DNA直接测序技术对患儿KCNJ11

  2. Clinical and molecular evidence of abnormal processing and trafficking of the vasopressin preprohormone in a large kindred with familial neurohypophyseal diabetes insipidus due to a signal peptide mutation

    DEFF Research Database (Denmark)

    Siggaard, C; Rittig, S; Corydon, T J

    1999-01-01

    The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease characterized by postnatal onset of polyuria and a deficient neurosecretion of the antidiuretic hormone, arginine vasopressin (AVP). Since 1991, adFNDI has been linked to 31 different mutations ...

  3. Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: Different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation

    Energy Technology Data Exchange (ETDEWEB)

    Hanna, M.G.; Nelson, I.; Sweeney, M.G.; Cooper, J.M.; Watkins, P.J.; Morgan-Hughes, J.A.; Harding, A.E. [Kings College Hospital, London (United Kingdom)

    1995-05-01

    We report the clinical, biochemical, and molecular genetic findings in a family with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA glutamic acid mutation at position 14709. The proband and his sister presented with congenital myopathy and mental retardation and subsequently developed cerebellar ataxia. Other family members had either adult-onset diabetes mellitus with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies. Biochemical studies of muscle mitochondria showed reduced complex I and IV activities. The mtDNA mutation was heteroplasmic in blood and muscle in all matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures containing high proportions of mutant mtDNA exhibited impaired mitochondrial translation. These observations indicate that mtDNA tRNA point mutations should be considered in the differential diagnosis of congenital myopathy. In addition they illustrate the diversity of phenotypes associated with this mutation in the same family and further highlight the association between mtDNA mutations and diabetes mellitus. 43 refs., 4 figs., 1 tab.

  4. Mitchell-Riley Syndrome: A Novel Mutation in RFX6 Gene

    Directory of Open Access Journals (Sweden)

    Marta Zegre Amorim

    2015-01-01

    Full Text Available A novel RFX6 homozygous missense mutation was identified in an infant with Mitchell-Riley syndrome. The most common features of Mitchell-Riley syndrome were present, including severe neonatal diabetes associated with annular pancreas, intestinal malrotation, gallbladder agenesis, cholestatic disease, chronic diarrhea, and severe intrauterine growth restriction. Perijejunal tissue similar to pancreatic tissue was found in the submucosa, a finding that has not been previously reported in this syndrome. This case associating RFX6 mutation with structural and functional pancreatic abnormalities reinforces the RFX6 gene role in pancreas development and β-cell function, adding information to the existent mutation databases.

  5. A novel -192c/g mutation in the proximal P2 promoter of the hepatocyte nuclear factor-4 alpha gene (HNF4A) associates with late-onset diabetes

    DEFF Research Database (Denmark)

    Ek, Jakob; Hansen, Sara P; Lajer, Maria;

    2006-01-01

    of the P2 promoter and the associated exon 1D of HNF4A for variations associated with diabetes in 114 patients with type 2 diabetes, 72 MODYX probands, and 85 women with previous gestational diabetes mellitus. A -192c/g mutation was found in five patients. We screened 1,587 diabetic subjects and 4......,812 glucose-tolerant subjects for the -192c/g mutation and identified 5 diabetic and 1 glucose-tolerant mutation carriers (P=0.004). Examination of the families showed that carriers of the -192c/g mutation had a significantly impaired glucose-stimulated insulin release and lower levels of serum total...

  6. A novel mutation MT-COIII m.9267G>C and MT-COI m.5913G>A mutation in mitochondrial genes in a Tunisian family with maternally inherited diabetes and deafness (MIDD) associated with sever nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Tabebi, Mouna, E-mail: mouna.biologiste@yahoo.com [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Mkaouar-Rebai, Emna [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Mnif, Mouna [Service d' endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Kallabi, Fakhri; Ben Mahmoud, Afif [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Ben Saad, Wafa; Charfi, Nadia [Service d' endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Keskes-Ammar, Leila; Kamoun, Hassen [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Abid, Mohamed [Service d' endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Fakhfakh, Faiza, E-mail: faiza.fakhfakh@gmail.com [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia)

    2015-04-10

    Mitochondrial diabetes (MD) is a heterogeneous disorder characterized by a chronic hyperglycemia, maternal transmission and its association with a bilateral hearing impairment. Several studies reported mutations in mitochondrial genes as potentially pathogenic for diabetes, since mitochondrial oxidative phosphorylation plays an important role in glucose-stimulated insulin secretion from beta cells. In the present report, we studied a Tunisian family with mitochondrial diabetes (MD) and deafness associated with nephropathy. The mutational analysis screening revealed the presence of a novel heteroplasmic mutation m.9276G>C in the mitochondrial COIII gene, detected in mtDNA extracted from leukocytes of a mother and her two daughters indicating that this mutation is maternally transmitted and suggest its implication in the observed phenotype. Bioinformatic tools showed that m.9267G>C mutation (p.A21P) is « deleterious » and it can modify the function and the stability of the MT-COIII protein by affecting the assembly of mitochondrial COX subunits and the translocation of protons then reducing the activity of the respective OXPHOS complexes of ATP synthesis. The nonsynonymous mutation (p.A21P) has not been reported before, it is the first mutation described in the COXIII gene which is related to insulin dependent mitochondrial diabetes and deafness and could be specific to the Tunisian population. The m.9267G>C mutation was present with a nonsynonymous inherited mitochondrial homoplasmic variation MT-COI m.5913 G>A (D4N) responsible of high blood pressure, a clinical feature detected in all explored patients. - Highlights: • MT-COX3 m.9267G>C (p.A21P), heteroplasmic substitution, is not reported in any database. • m.9267G>C can be responsible of the MIDD associated with nephropaty. • This substitution can modify the function and the stability of the MT-CO3 protein. • This substitution can modify MT-CO3 structure (2D and 3D). • MT-COX3 m.9267G>C is associated

  7. Neonatally-induced diabetes: lipid profile outcomes and oxidative stress status in adult rats Diabete induzido no período neonatal: repercussões no perfil lipídico e avaliação dos marcadores de estresse oxidativo na vida adulta de ratas

    Directory of Open Access Journals (Sweden)

    Yuri Karen Sinzato

    2009-01-01

    Full Text Available BACKGROUND: Experimental models are developed for the purpose of enhancing the understanding of the pathophysiological mechanisms involved in diabetes. Experimental findings lead to the development of treatment strategies to maintain metabolic conditions as close to normal as possible. There are several reports about streptozotocin induced mild diabetes to reproduce type 2 diabetes. However, studies about the interaction among glucose levels, lipid profile, and oxidative stress in these animals remain insufficient. Therefore, this study evaluated these parameters in blood samples from adult Wistar rats treated neonatally with streptozotocin. METHODS: Female newborn Wistar rats received streptozotocin (70 mg/kg, i.p. on the 5th day of life (n5-STZ. Glycemia was measured in the 3rd and 4th month of life. At the end of the 4th month, blood samples were collected and processed for lipid profile and oxidative stress measurements. RESULTS: Glycemia of n5-STZ rats were significantly higher compared to those of control rats (p0.05 in the n5-STZ animals when compared to control group. However n5-STZ animals showed a significant decreased HDL-cholesterol rate (pINTRODUÇÃO: Modelos experimentais são desenvolvidos com propósito de ampliar o entendimento dos mecanismos fisiopatológicos envolvidos no diabete. Os achados experimentais levam ao desenvolvimento de tratamentos alternativos para a manutenção das condições metabólicas normais. Existem vários estudos sobre o diabete induzido por streptozotocin mimetizando o quadro clínico do DM2. No entanto, a interação entre os níveis de glicose, perfil lipídico e estresse oxidativo nestes animais são escassos. Portanto, o objetivo do trabalho foi avaliar estes parâmetros em ratas Wistar adultas com diabete induzido com streptozotocin no período neonatal. MÉTODOS: Fêmeas recém-nascidas receberam streptozotocin (70mg/Kg, ip no 5º dia de vida (n5-STZ. A glicemia foi medida no terceiro e quarto

  8. Analysis of large sample screening for mutational sites at common deafness-related gene in neonates%新生儿常见致聋基因突变位点的大样本筛查分析

    Institute of Scientific and Technical Information of China (English)

    孙雪晶; 席作明; 张静; 刘保彦; 黄鑫; 周林; 赵青

    2016-01-01

    Objective To investigate the distribution of mutational sites of common deafness-related susceptibility genes in neonates so as to lay a foundation for clinical interventions.Methods A total of 11121 cases of neonates were screened for mutational sites of deafness-related susceptibility genes by using real-time fluorescence quantitative polymerasechain reaction technology.Screened sites were six mutational sites at three common deafness-related genes in China.Those genes were GJB2 (c.235 del C, c.299-300 del AT), mtDNA 12S rRNA (c.1494 C>T, c.1555 A>C) and SLC26A4 (c.2168 A>G, c.IVS7-2 A>G).Gene sequencing and hearing diagnosis were performed for individuals with mutant genes.Results Among 11121 neonates, 517 cases were deafness-related mutant gene carriers, including 39 cases of homozygous mutations, 469 cases of heterozygous mutations, 2 cases of single-gene compound heterozygous mutations and 7 cases of double-gene compound heterozygous mutations.The positive rate was 4.65%.Among 517 cases of genetic mutations, 286 cases of GJB2 mutations (including 2 cases of compound heterozygous mutations of c.235 del C and c.299-300 del AT), 189 cases of mtDNA 12S rRNA gene mutations, 35 cases of SLC26A4 gene mutations and 7 cases of double-gene compound heterozygous mutations were included.The positive rate of deafness-related genetic mutations in females neonates was higher than that in males (χ2 =8.653, PG of gene SLC26A4.However, the mutation rate is extremely low at the mutation site c.1494C>T of mtDNA 12S rRNA, indicating that it is not a hot-spot deafness-related gene in this area.In addition, there is significant difference in positive rate of mutation between female and male neonates.The preceding results have provided important evidences for directing the screening of deafness-related genes in this area.%目的 探讨新生儿常见聋病易感基因突变位点分布情况,为临床干预奠定基础.方法 采用实时荧光聚合酶链反应(PCR)技术对11121

  9. Impacto do diabetes gestacional nos desfechos neonatais: uma coorte retrospectiva = Impact of gestational diabetes on neonatal outcomes: a retrospective cohort study

    OpenAIRE

    Amaral,Augusto Radünz do

    2015-01-01

    Objetivos: Avaliar os desfechos neonatais em gestantes diagnosticadas com diabetes mellitus gestacional (DMG) Métodos: Coorte retrospectiva com 522 puérperas, sendo 255 pacientes com diagnóstico de DMG pelos critérios da International Association of the Diabetes and Pregnancy Study Groups (IADPSG) e 267 pacientes sem DMG, tendo sido este último grupo selecionado por sorteio. Foram avaliadas associações entre DMG e a ocorrência de desfechos neonatais adversos, entre os quais prematuridade, ...

  10. Decreased concentrations of the lipoprotein lipase inhibitor angiopoietin-like protein 4 and increased serum triacylglycerol are associated with increased neonatal fat mass in pregnant women with gestational diabetes mellitus.

    Science.gov (United States)

    Ortega-Senovilla, Henar; Schaefer-Graf, Ute; Meitzner, Katrin; Abou-Dakn, Michael; Herrera, Emilio

    2013-08-01

    Angiopoietin-like protein 4 (ANGPTL4) is an extracellular inhibitor of lipoprotein lipase (LPL) activity. No studies have been done in pregnancy in which hypertriglyceridemia and tissue-specific changes in LPL activity are present. The objective of the study was to determine the relationship between neonatal fat mass (FM) and concentrations of ANGPTL4 and triacylglycerols (TAG) in maternal and cord serum of pregnant women with gestational diabetes mellitus (GDM) compared with controls. Maternal blood samples (control, n = 90, and GDM, n= 80) and umbilical cord blood were drawn before and after vaginal delivery, respectively. Control and GDM subjects were grouped separately into 3 subgroups, according to neonatal FM: 0-25th percentiles, 25th-75th percentiles, and 75th-100th percentiles. Glucose, insulin, TAG, nonesterified fatty acids (NEFAs), and ANGPTL4 were determined in maternal and neonatal serum. Age and pregestational body mass index did not differ between GDM and control women in any subgroups. Maternal serum of GDM pregnant women who delivered the newborn with the highest FM showed the highest concentrations of TAG and NEFAs and lowest concentration of ANGPTL4, despite glucose and insulin concentrations being independent of changes in neonatal FM. However, cord serum of neonates of GDM patients with the highest FM showed higher concentrations of insulin and lower concentrations of TAG than those with lower neonatal FM but no significant differences in NEFAs or ANGPTL4 concentrations. In well-controlled GDM pregnancies, decreased maternal ANGPTL4 concentrations and a gradient of TAG toward the fetus are related with higher neonatal FM. However, in GDM fetuses with the highest FM, the potential effect of ANGPTL4 inhibiting adipose tissue LPL activity could be overcome by their hyperinsulinemia.

  11. Acción de la estreptozotocina en un modelo experimental de inducción neonatal de la diabetes

    Directory of Open Access Journals (Sweden)

    Leticia Bequer

    2016-06-01

    Conclusiones. La inyección subcutánea de una dosis de 100 mg/kg de estreptozotocina en el segundo día después del nacimiento logró mayor efectividad en la inducción de diabetes moderada en ratas Wistar adultas.

  12. Associations of Body Mass Index (Maternal BMI) and Gestationel Diabetes Mellitus with Neonatal and Maternal Pregnancy Outcomes in a Multicentre European Database (Diabetes and Pregnancy Vitamin D and Lifestyle Intervention for Gestational Diabetes Mellitus Prevention)

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth Reinhardt

    2012-01-01

    section, macrosomia and neonatal morbidities. Results. Comparison of databases identified reporting differences between countries due to the inclusion of true population based samples or pregnancies from specialised tertiary centres, resulting in higher prevalences of GDM for some countries. The analysis...

  13. A novel missense mutation in the signal peptide of the human POMC gene: a possible additional link between early-onset type 2 diabetes and obesity.

    Science.gov (United States)

    Mencarelli, Monica; Zulian, Alessandra; Cancello, Raffaella; Alberti, Luisella; Gilardini, Luisa; Di Blasio, Anna Maria; Invitti, Cecilia

    2012-12-01

    Rare mutations in several genes have a critical role in the control of homeostatic mechanisms such as food-intake, energy balance and glucose metabolism. In this study, we performed a mutational screening in a 58-year-old woman presenting early-onset type 2 diabetes and central obesity. The entire coding regions of MC4R, MC3R, HNF1A, GCK and POMC (pro-opiomelanocortin) genes were analyzed by direct sequencing. A new missense mutation was identified within the POMC gene signal peptide sequence, resulting in a heterozygous substitution of an arginine for a glycine at codon 15 (p.A15G) that was excluded in 300 healthy normal weight controls. The mutation segregated in the family and was associated with overweight, type 2 diabetes, hypertension and coronary heart disease in the carriers. Functional studies demonstrated that POMC protein was not detectable in β-TC3 cells transfected with A15G-POMC vector as well as in their culture media, despite POMC mRNA levels were comparable for amount and stability to those of wild-type-transfected cells. In silico RNA folding prediction indicated that the mutation gives rise to a different RNA secondary structure, suggesting that it might affect translation and protein synthesis. To the best of our knowledge, this is the first report addressing the functional consequences of a mutation in the signal peptide of POMC. These findings further support the hypothesis that POMC-derived peptides might have a role in the control of peripheral glucose metabolism and suggest that disruption of central POMC secretion might represent an additional link between type 2 diabetes and obesity.

  14. A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2

    DEFF Research Database (Denmark)

    Hinrichs, Gitte R; Hansen, Louise H; Nielsen, Maria R

    2016-01-01

    Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome of inappropr...... administration. While a similar urine exosome release rate was shown between probands and controls by western blotting for the marker ALIX, there was a selective decrease in exosome aquaporin-2 versus aquaporin-1 protein in probands compared to controls....

  15. A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2

    DEFF Research Database (Denmark)

    Hinrichs, Gitte R; Hansen, Louise H; Nielsen, Maria R

    2016-01-01

    Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome of inappropr...... administration. While a similar urine exosome release rate was shown between probands and controls by western blotting for the marker ALIX, there was a selective decrease in exosome aquaporin-2 versus aquaporin-1 protein in probands compared to controls....

  16. Diabetes

    OpenAIRE

    Smith, Paul

    2003-01-01

    Derbyshire general practitioner Stuart Bootle has had diabetes for 20 years. He speaks to Paul Smith, who has type 1 diabetes himself, about the trials and tribulations of being on the receiving end of NHS care

  17. A novel mitochondrial DNA deletion in a patient with Pearson syndrome and neonatal diabetes mellitus provides insight into disease etiology, severity and progression.

    Science.gov (United States)

    Chen, Xin-Yu; Zhao, Si-Yu; Wang, Yan; Wang, Dong; Dong, Chang-Hu; Yang, Ying; Wang, Zhi-Hua; Wu, Yuan-Ming

    2016-07-01

    Pearson syndrome (PS) is a rare, mitochondrial DNA (mtDNA) deletion disorder mainly affecting hematopoietic system and exocrine pancreas in early infancy, which is characterized by multi-organ involvement, variable manifestations and poor prognosis. Since the clinical complexity and uncertain outcome of PS, the ability to early diagnose and anticipate disease progression is of great clinical importance. We described a patient with severe anemia and hyperglycinemia at birth was diagnosed with neonatal diabetes mellitus, and later with PS. Genetic testing revealed that a novel mtDNA deletion existed in various non-invasive tissues from the patient. The disease course was monitored by mtDNA deletion heteroplasmy and mtDNA/nucleus DNA genome ratio in different tissues and at different time points, showing a potential genotype-phenotype correlation. Our findings suggest that for patient suspected for PS, it may be therapeutically important to first perform detailed mtDNA analysis on non-invasive tissues at the initial diagnosis and during disease progression.

  18. Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Ying Yang

    2016-01-01

    Full Text Available Maturity-onset diabetes of the young (MODY is characterized by the onset of diabetes before the age of 25 years, positive family history, high genetic predisposition, monogenic mutations, and an autosomal dominant mode of inheritance. Here, we aimed to investigate the mutations and to characterize the phenotypes of a Han Chinese family with early-onset maternally inherited type 2 diabetes. Detailed clinical assessments and genetic screening for mutations in the HNF4α, GCK, HNF-1α, IPF-1, HNF1β, and NEUROD1 genes were carried out in this family. One HNF4A mutation (p.T130I and two HNF1A polymorphisms (p.I27L and p.S487N were identified. Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulated HNF4A expression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes. We demonstrated that mutation p.T130I in HNF4A was pathogenic as were the predicted polymorphisms p.I27L and p.S487N in HNF1A by genetic and functional analysis. Our results show that mutations in HNF4A and HNF1A genes might account for this early-onset inherited type 2 diabetes.

  19. Segregation patterns of a novel mutation in the mitochondrial tRNA glutamic acid gene associated with myopathy and diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Hao, H.; Moraes, C.T. [Univ. of Miami, FL (United States); Bonilla, E.; Manfredi, G.; DiMauro, S. [Columbia Univ., NY (United States)

    1995-05-01

    We have identified a novel mtDNA mutation in a 29-year-old man with myopathy and diabetes mellitus. This T{r_arrow}C transition at mtDNA position 14709 alters an evolutionarily conserved nucleotide in the region specifying for the anticodon loop of the mitochondrial tRNA{sup Glu}. The nt-14709 mutation was heteroplasmic but present at very high levels in the patient`s muscle, white blood cells (WBCs), and hair follicles; lower proportions of mutated mtDNA were observed in WBCs and hair follicles of all examined maternal relatives. In the patient`s muscle, abnormal fibers showed mitochondrial proliferation, severe focal defects in cytochrome c oxidase activity, and absence of cross-reacting material for mitochondrially synthesized polypeptides. These fibers had higher levels of mutated mtDNA than did surrounding {open_quotes}normal{close_quotes} fibers. Although the percentage of mutated mtDNA in WBCs from family members were distributed around the percentage observed in the mothers, the pattern was different in hair follicles, where the mutated population tended to increase in subsequent generations. PCR/RFLP analysis of single hair showed that the intercellular variations in the percentage of mutated mtDNA differed among family members, with younger generations having a more homogeneous distribution of mutated mtDNA in different hair follicles. These results suggests that the intercellular distribution of the mutated and wild-type mtDNA populations may drift toward homogeneity in subsequent generations. 43 refs., 4 figs., 1 tab.

  20. Epigenetics in neonatal diseases

    Institute of Scientific and Technical Information of China (English)

    XU Xue-feng; DU Li-zhong

    2010-01-01

    Objective To review the role of epigenetic regulation in neonatal diseases and better understand Barker's "fetal origins of adult disease hypothesis".Data sources The data cited in this review were mainly obtained from the articles published in Medline/PubMed between January 1953 and December 2009.Study selection Articles associated with epigenetics and neonatal diseases were selected.Results There is a wealth of epidemiological evidence that lower birth weight is strongly correlated with an increased risk of adult diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular disease. This phenomenon of fetal origins of adult disease is strongly associated with fetal insults to epigenetic modifications of genes. A potential role of epigenetic modifications in congenital disorders, transient neonatal diabetes mellitus (TNDM), intrauterine growth retardation (IUGR), and persistent pulmonary hypertension of the newborn (PPHN) have been studied.Conclusions Acknowledgment of the role of these epigenetic modifications in neonatal diseases would be conducive to better understanding the pathogenesis of these diseases, and provide new insight for improved treatment and prevention of later adult diseases.

  1. Clinical and molecular characterization of a novel INS mutation identified in patients with MODY phenotype.

    Science.gov (United States)

    Piccini, Barbara; Artuso, Rosangela; Lenzi, Lorenzo; Guasti, Monica; Braccesi, Giulia; Barni, Federica; Casalini, Emilio; Giglio, Sabrina; Toni, Sonia

    2016-11-01

    Correct diagnosis of Maturity-Onset Diabetes of the Young (MODY) is based on genetic tests requiring an appropriate subject selection by clinicians. Mutations in the insulin (INS) gene rarely occur in patients with MODY. This study is aimed at determining the genetic background and clinical phenotype in patients with suspected MODY. 34 patients with suspected MODY, negative for mutations in the GCK, HNF1α, HNF4α, HNF1β and PDX1 genes, were screened by next generation sequencing (NGS). A heterozygous INS mutation was identified in 4 members of the same family. First genetic tests performed identified two heterozygous silent nucleotide substitutions in MODY3/HNF1α gene. An ineffective attempt to suspend insulin therapy, administering repaglinide and sulphonylureas, was made. DNA was re-sequenced by NGS investigating a set of 102 genes. Genes implicated in the pathway of pancreatic β-cells, candidate genes for type 2 diabetes mellitus and genes causative of diabetes in mice were selected. A novel heterozygous variant in human preproinsulin INS gene (c.125T > C) was found in the affected family members. The new INS mutation broadens the spectrum of possible INS phenotypes. Screening for INS mutations is warranted not only in neonatal diabetes but also in MODYx patients and in selected patients with type 1 diabetes mellitus negative for autoantibodies. Subjects with complex diseases without a specific phenotype should be studied by NGS because Sanger sequencing is ineffective and time consuming in detecting rare variants.

  2. A novel mutation m.8561C>G in MT-ATP6/8 causing a mitochondrial syndrome with ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotropic hypogonadism.

    Science.gov (United States)

    Kytövuori, Laura; Lipponen, Joonas; Rusanen, Harri; Komulainen, Tuomas; Martikainen, Mika H; Majamaa, Kari

    2016-11-01

    Defects in the respiratory chain or mitochondrial ATP synthase (complex V) result in mitochondrial dysfunction that is an important cause of inherited neurological disease. Two of the subunits of complex V are encoded by MT-ATP6 and MT-ATP8 in the mitochondrial genome. Pathogenic mutations in MT-ATP6 are associated with the Leigh syndrome, the syndrome of neuropathy, ataxia, and retinitis pigmentosa (NARP), as well as with non-classical phenotypes, while MT-ATP8 is less frequently mutated in patients with mitochondrial disease. We investigated two adult siblings presenting with features of cerebellar ataxia, peripheral neuropathy, diabetes mellitus, sensorineural hearing impairment, and hypergonadotropic hypogonadism. As the phenotype was suggestive of mitochondrial disease, mitochondrial DNA was sequenced and a novel heteroplasmic mutation m.8561C>G in the overlapping region of the MT-ATP6 and MT-ATP8 was found. The mutation changed amino acids in both subunits. Mutation heteroplasmy correlated with the disease phenotype in five family members. An additional assembly intermediate of complex V and increased amount of subcomplex F1 were observed in myoblasts of the two patients, but the total amount of complex V was unaffected. Furthermore, intracellular ATP concentration was lower in patient myoblasts indicating defective energy production. We suggest that the m.8561C>G mutation in MT-ATP6/8 is pathogenic, leads biochemically to impaired assembly and decreased ATP production of complex V, and results clinically in a phenotype with the core features of cerebellar ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotropic hypogonadism.

  3. Expression of a dominant negative PKA mutation in the kidney elicits a diabetes insipidus phenotype.

    Science.gov (United States)

    Gilbert, Merle L; Yang, Linghai; Su, Thomas; McKnight, G Stanley

    2015-03-15

    PKA plays a critical role in water excretion through regulation of the production and action of the antidiuretic hormone arginine vasopressin (AVP). The AVP prohormone is produced in the hypothalamus, where its transcription is regulated by cAMP. Once released into the circulation, AVP stimulates antidiuresis through activation of vasopressin 2 receptors in renal principal cells. Vasopressin 2 receptor activation increases cAMP and activates PKA, which, in turn, phosphorylates aquaporin (AQP)2, triggering apical membrane accumulation, increased collecting duct permeability, and water reabsorption. We used single-minded homolog 1 (Sim1)-Cre recombinase-mediated expression of a dominant negative PKA regulatory subunit (RIαB) to disrupt kinase activity in vivo and assess the role of PKA in fluid homeostasis. RIαB expression gave rise to marked polydipsia and polyuria; however, neither hypothalamic Avp mRNA expression nor urinary AVP levels were attenuated, indicating a primary physiological effect on the kidney. RIαB mice displayed a marked deficit in urinary concentrating ability and greatly reduced levels of AQP2 and phospho-AQP2. Dehydration induced Aqp2 mRNA in the kidney of both control and RIαB-expressing mice, but AQP2 protein levels were still reduced in RIαB-expressing mutants, and mice were unable to fully concentrate their urine and conserve water. We conclude that partial PKA inhibition in the kidney leads to posttranslational effects that reduce AQP2 protein levels and interfere with apical membrane localization. These findings demonstrate a distinct physiological role for PKA signaling in both short- and long-term regulation of AQP2 and characterize a novel mouse model of diabetes insipidus.

  4. Heteroplasmy Level of the Mitochondrial tRNALeu(UUR) A3243G Mutation in a Chinese Family Is Positively Associated with Earlier Age-of-onset and Increasing Severity of Diabetes

    Institute of Scientific and Technical Information of China (English)

    Shi Zhang; An-li Tong; Yun Zhang; Min Nie; Yu-xiu Li; Heng Wang

    2009-01-01

    Objective To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. Methods Genomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations. Results Family members on the maternal side all harbored the tRNALeu(UUR) A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980 (P = 0.02). Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found. Conclusions The main cause of diabetes in this pedigree is the tRNALeu(UUR) A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNALeu(UUR) A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.

  5. Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes.

    Science.gov (United States)

    Yang, Yisheng; Chan, Lawrence

    2016-06-01

    To date, more than 30 genes have been linked to monogenic diabetes. Candidate gene and genome-wide association studies have identified > 50 susceptibility loci for common type 1 diabetes (T1D) and approximately 100 susceptibility loci for type 2 diabetes (T2D). About 1-5% of all cases of diabetes result from single-gene mutations and are called monogenic diabetes. Here, we review the pathophysiological basis of the role of monogenic diabetes genes that have also been found to be associated with common T1D and/or T2D. Variants of approximately one-third of monogenic diabetes genes are associated with T2D, but not T1D. Two of the T2D-associated monogenic diabetes genes-potassium inward-rectifying channel, subfamily J, member 11 (KCNJ11), which controls glucose-stimulated insulin secretion in the β-cell; and peroxisome proliferator-activated receptor γ (PPARG), which impacts multiple tissue targets in relation to inflammation and insulin sensitivity-have been developed as major antidiabetic drug targets. Another monogenic diabetes gene, the preproinsulin gene (INS), is unique in that INS mutations can cause hyperinsulinemia, hyperproinsulinemia, neonatal diabetes mellitus, one type of maturity-onset diabetes of the young (MODY10), and autoantibody-negative T1D. Dominant heterozygous INS mutations are the second most common cause of permanent neonatal diabetes. Moreover, INS gene variants are strongly associated with common T1D (type 1a), but inconsistently with T2D. Variants of the monogenic diabetes gene Gli-similar 3 (GLIS3) are associated with both T1D and T2D. GLIS3 is a key transcription factor in insulin production and β-cell differentiation during embryonic development, which perturbation forms the basis of monogenic diabetes as well as its association with T1D. GLIS3 is also required for compensatory β-cell proliferation in adults; impairment of this function predisposes to T2D. Thus, monogenic forms of diabetes are invaluable "human models" that have

  6. Neonatal anemia.

    Science.gov (United States)

    Aher, Sanjay; Malwatkar, Kedar; Kadam, Sandeep

    2008-08-01

    Neonatal anemia and the need for red blood cell (RBC) transfusions are very common in neonatal intensive care units. Neonatal anemia can be due to blood loss, decreased RBC production, or increased destruction of erythrocytes. Physiologic anemia of the newborn and anemia of prematurity are the two most common causes of anemia in neonates. Phlebotomy losses result in much of the anemia seen in extremely low birthweight infants (ELBW). Accepting a lower threshold level for transfusion in ELBW infants can prevent these infants being exposed to multiple donors.

  7. Diabetes.

    Science.gov (United States)

    Lomberk, Gwen

    2009-01-01

    Pancreatologists have often divided research of the pancreas based upon the origin of the function or disease, namely the endocrine or exocrine pancreas. In fact, as a result, many of our meetings and conferences have followed separate paths. Interestingly, among patients with chronic pancreatitis and pancreatic cancer, both disorders of the exocrine pancreas, diabetes is common. However, the clinical features of the diabetes associated with these two differ. Peripheral insulin resistance and hyperinsulinemia are the predominant diabetic traits in pancreatic cancer, while reduced islet cell mass and impaired insulin secretion are observed more often in chronic pancreatitis. The causal relationship between diabetes and pancreatic cancer remains an intriguing but unanswered question. Since diabetes often precedes pancreatic cancer, it is regarded as a potential risk factor for malignancy. On the other hand, there remains the possibility that pancreatic cancer secretes diabetogenic factors. Regardless of how the science ultimately illuminates this issue, there is increasing interest in utilizing screening for diabetes to aid early detection of pancreatic tumor lesions. Therefore, in this issue of Pancreatology and the Web, we explore the topic of diabetes to keep us alert to this very important association, even if we study diseases of the exocrine pancreas.

  8. Diabetes

    DEFF Research Database (Denmark)

    Damm, Peter; Mathiesen, Elisabeth R

    2015-01-01

    For >30 years, insulin has been the drug of choice for the medical treatment of gestational diabetes mellitus. However, the use of oral hypoglycaemic agents has increased during the past 1–2 decades, so a recent comparison of treatment with glibenclamide, metformin or insulin in women with gestat......For >30 years, insulin has been the drug of choice for the medical treatment of gestational diabetes mellitus. However, the use of oral hypoglycaemic agents has increased during the past 1–2 decades, so a recent comparison of treatment with glibenclamide, metformin or insulin in women...... with gestational diabetes mellitus is highly relevant....

  9. Diabetes

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — These datasets provide de-identified insurance data for diabetes. The data is provided by three managed care organizations in Allegheny County (Gateway Health Plan,...

  10. 线粒体基因突变与糖尿病的相关性研究进展%Study on Mitochondrial Gene Mutation Associated with Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    王鉴; 顾鸣敏

    2012-01-01

    Mutations in mitochondrail DNA (mtDNA) can lead to various genetic diseases, including diabetes mellitus. The most common mutation associated with mtDNA mutation is tRNALeu (UUR)] 3243 A→G. This article describes the links between mtDNA and diabetes mellitus, and makes an introduction of clinical characteristics and pathogenesis of diabetes mellitus, summarizes several mu-tational genetic loci associated with diabetes mellitus, and mainly introduces mutational sites m.3243A→G.3310C→T, 16189T→C associated with pathophysiology of maternally inherited diabetes. The authors believe that the study of genetic loci mutations provides new insights of diabetic pathogenesis and offers new directions for treatment of diabetes mellitus.%线粒体DNA(mtDNA)突变可引起多种遗传性疾病,其中包括糖尿病.与mtDNA突变相关的糖尿病中最常见的变异是tRNALeu(UUR)] 3243 A→G.文章描述了mtDNA线粒体突变与糖尿病的相关性,介绍了线粒体糖尿病的临床特点和发病机制,概括了线粒体糖尿病相关变异基因位点,重点介绍了m.3243A→G、3310C→T、16189T→C基因突变与线粒体糖尿病病理生理的联系.文章认为mtDNA突变位点的研究为糖尿病的发生机制提供新的视角,也为糖尿病的治疗提供了新方向.

  11. An emerging, recognizable facial phenotype in association with mutations in GLI-similar 3 (GLIS3).

    Science.gov (United States)

    Dimitri, Paul; De Franco, Elisa; Habeb, Abdelhadi M; Gurbuz, Fatih; Moussa, Khairya; Taha, Doris; Wales, Jerry K H; Hogue, Jacob; Slavotinek, Anne; Shetty, Ambika; Balasubramanian, Meena

    2016-07-01

    Neonatal diabetes and hypothyroidism (NDH) syndrome was first described in 2003 in a consanguineous Saudi Arabian family where two out of four siblings were reported to have presented with proportionate IUGR, neonatal non-autoimmune diabetes mellitus, severe congenital hypothyroidism, cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterized by enlarged kidneys and multiple small cysts with deficient cortico-medullary junction differentiation and normal kidney function. There was minor facial dysmorphism (depressed nasal bridge, large anterior fontanelle, long philtrum) reported but no facial photographs were published. Mutations in the transcription factor GLI-similar 3 (GLIS3) gene in the original family and two other families were subsequently reported in 2006. All affected individuals had neonatal diabetes, congenital hypothyroidism but glaucoma and liver and kidney involvement were less consistent features. Detailed descriptions of the facial dysmorphism have not been reported previously. In this report, we describe the common facial dysmorphism consisting of bilateral low-set ears, depressed nasal bridge with overhanging columella, elongated, upslanted palpebral fissures, persistent long philtrum with a thin vermilion border of the upper lip in a cohort of seven patients with GLIS3 mutations and report the emergence of a distinct, probably recognizable facial gestalt in this group which evolves with age. © 2016 Wiley Periodicals, Inc.

  12. Mutations in exons 10 and 11 of human glucokinase result in conformational variations in the active site of the structure contributing to poor substrate binding - explains hyperglycemia in type 2 diabetic patients.

    Science.gov (United States)

    Yellapu, Nandakumar; Mahto, Manoj Kumar; Valasani, Koteswara Rao; Sarma, P V G K; Matcha, Bhaskar

    2015-01-01

    Mutations in the glucokinase (GK) gene play a critical role in the establishment of type 2 diabetes. In our earlier study, R308K mutation in GK in a clinically proven type 2 diabetic patient showed, structural and functional variations that contributed immensely to the hyperglycemic condition. In the extension of this work, a cohort of 30 patients with established type 2 diabetic condition were chosen and the exons 10 and 11 of GK were PCR-amplified and sequenced. The sequence alignment showed A379S, D400Y, E300A, E395A, E395G, H380N, I348N, L301M, M298I, M381G, M402R, R308K, R394P, R397S, and S398R mutations in 12 different patients. The structural analysis of these mutated GKs, showed a variable number of β-α-β units, hairpins, β-bulges, strands, helices, helix-helix interactions, β-turns, and γ-turns along with the RMSD variations when compared to wild-type GK. Molecular modeling studies revealed that the substrate showed variable binding orientations and could not fit into the active site of these mutated structures; moreover, it was expelled out of the conformations. Therefore, these structural variations in GK due to mutations could be one of the strongest reasons for the hyperglycemic levels in these type 2 diabetic patients.

  13. Altered promoter recycling rates contribute to dominant-negative activity of human peroxisome proliferator-activated receptor-gamma mutations associated with diabetes.

    Science.gov (United States)

    Li, Gang; Leff, Todd

    2007-04-01

    The transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma) plays an important role in regulating lipid and glucose metabolism and improves insulin sensitivity in diabetic patients when activated by thiazolidinedione drugs. Several loss-of-function mutations in PPARgamma have been identified that cause lipodystrophy and diabetes in humans. Because affected individuals are heterozygotes and have one normal PPARgamma allele, it is of interest to know whether these mutations act in a dominant-negative fashion to inhibit the activity of the wild-type (WT) receptor. Here we compare the molecular phenotypes of two previously identified PPARgamma mutations: P467L, reported to be dominant negative; and F388L, reported to be devoid of dominant-negative activity. We developed a competitive chromatin immunoprecipitation assay to measure the relative ability of mutant PPARgamma to compete with WT receptor for binding to a PPAR regulatory element (PPRE)-containing promoter. By determining the ratio of mutant and WT receptors bound to a PPRE over time, we estimated the relative promoter turnover rate of each receptor. This assay demonstrated that PPARgamma bearing the P467L had a reduced promoter turnover rate compared with the F388L receptor, and over time out-competed the WT receptor for promoter binding sites. We propose that the P467L receptor is dominant negative because in a cell containing both WT and mutant receptors, the majority of the PPAR-regulated promoters will be occupied by the transcriptionally defective mutant receptor. In contrast, the F388L mutation lacks dominant-negative activity because its more rapid promoter turnover rate prevented it from out-competing the WT receptor for promoter binding sites.

  14. Tirosinemia neonatal Neonatal tyrosinemia

    Directory of Open Access Journals (Sweden)

    Rafael J. Manotas Cabarcas

    1995-04-01

    Full Text Available Mediante la técnica de Udenfriend y Cooper, se midieron los niveles de tirosina en la sangre del cordón de 26 prematuros y 31 niños de término, con el fin de comparar las concentraciones según la edad gestacional y detectar la presencia de la tirosinemia neonatal. Se encontró un caso de esta entidad en un niño de 31 semanas de edad gestacional, lo cual correspondió al 3.8% de los prematuros y al 1.8% del grupo total. La concentración de tirosina en el paciente fue de 53 JJ.M. El promedio de las concentraciones en los prematuros menores de 32 semanas fue de 16.8 :t 6.3 JJ.M; el de los niños entre 33 y 36 semanas fue de 19.3 :t 7.6 JJ.M y el de los niños de término, de 17.2 :t 9.4 JJ.M. Las pruebas estadísticas no mostraron tendencias ni diferencias significativas entre estas concentraciones. El promedio ponderado para el grupo total fue 17.7 :t 7.3 JJ.M. Se recomienda establecer programas de tamizaje para detectar este problema porque puede presentar repercusiones neurológicas posteriores.

    By means of the Udenfriend-Cooper technique, levels of tyrosine were measured in the cord blood of 26 preterm and 31 term Infants; the objective was to compare tyrosine concentrations according to gestational age and to detect the presence of neonatal tyrosinemia. A case of this disease was found In an Infant with 31 weeks of gestational age; this case represented 3.8% of preterm Infants and 1.8% of the total group. Average tyrosine concentration according to age was as follows: 16.8: ± 6.3  µM in Infants under 32 weeks of gestational age; 19.3: ±: 7.6 µM In those between 33 and 36 weeks and 17.2 : ±: 9.4 µM In the term Infants

  15. Neonatal trauma

    Energy Technology Data Exchange (ETDEWEB)

    Sorantin, Erich [Division of Pediatric Radiology, Department of Radiology, Medical University Graz, Auenbruggerplatz 9, A8036 Graz (Austria)]. E-mail: erich.sorantin@meduni-graz.at; Brader, Peter [Division of Pediatric Radiology, Department of Radiology, Medical University Graz, Auenbruggerplatz 9, A8036 Graz (Austria); Thimary, Felix [Division of Pediatric Radiology, Department of Radiology, Medical University Graz, Auenbruggerplatz 9, A8036 Graz (Austria)

    2006-11-15

    A variety of traumatic lesions can occur during the neonatal period. Some of those lesions are clearly birth injuries due to delivery and others are caused by necessary procedures during intensive care in critically ill neonates. As usual patient history must be known and knowledge about the typical complications is necessary in order to select the appropriate imaging modality and thus enabling correct interpretation of those investigations by the radiologist. The purpose of this article is to present typical neonatal injuries, describe the underlying pathomechanisms and aetiology as well as the imaging findings.

  16. Neonatal muscular manifestations in mitochondrial disorders.

    Science.gov (United States)

    Tulinius, Már; Oldfors, Anders

    2011-08-01

    During the last decade rapid development has occurred in defining nuclear gene mutations causing mitochondrial disease. Some of these newly defined gene mutations cause neonatal or early infantile onset of disease, often associated with severe progressive encephalomyopathy combined with other multi-organ involvement such as cardiomyopathy or hepatopathy and with early death. Findings suggesting myopathy in neonates are hypotonia, muscle weakness and wasting, and arthrogryposis. We aim to describe the clinical findings of patients with mitochondrial disease presenting with muscular manifestations in the neonatal period or in early infancy and in whom the genetic defect has been characterized. The majority of patients with neonatal onset of mitochondrial disease have mutations in nuclear genes causing dysfunction of the mitochondrial respiratory chain, leading to defective oxidative phosphorylation.

  17. 妊娠期糖尿病母亲新生儿早期并发症的临床观察%Clinical observation on early complications of neonates born by women with gestational diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    秦义倩; 刘莉; 周信英; 何国芳

    2013-01-01

    目的:探讨母亲妊娠期糖尿病对早期新生儿的影响.方法:对50例糖尿病母亲婴儿的临床资料进行回顾性分析,并与健康孕妇的新生儿进行对比.结果:糖尿病母亲婴儿低血糖、高胆红素血症、窒息、出生体重异常的发病率均明显高于对照组(P<0.05).结论:母亲妊娠期糖尿病为新生儿高危因素,新生儿低血糖、高胆红素血症、窒息、出生体重异常的发病率不低,值得临床关注.%Objective: To explore the effect of maternal gestational diabetes mellitus (GDM) on early neonates. Methods: The clinical data of 50 infants born by GDM women were analyzed retrospectively, then the results were compared with clinical data of 50 neonates with healthy women. Results: The incidences of hypoglycemia, hyperbilirubinemia, asphyxia, and abnormal birth weight of infants born by GDM women were statistically significantly higher than those in control group (P <0. 05) . Conclusion: Maternal GDM is one of high risk factors of neonates, the incidences of neonatal hypoglycemia, hyperbilirubinemia, asphyxia, and abnormal birth weight are high, which need more clinical attention.

  18. Neonatal onset autosomal dominant polycystic kidney disease (ADPKD) in a patient homozygous for a PKD2 missense mutation due to uniparental disomy.

    NARCIS (Netherlands)

    Losekoot, M.; Ruivenkamp, C.A.; Tholens, A.P.; Grimbergen, J.E.; Vijfhuizen, L.; Vermeer, S.; Dijkman, H.B.P.M.; Cornelissen, E.A.M.; Bongers, M.H.F.; Peters, D.J.

    2012-01-01

    Autosomal dominant polycystic kidney disease (ADPKD), due to a heterozygous mutation in PKD1 or PKD2, is usually an adult onset disease. Renal cystic disease is generally milder in PKD2 patients than in PKD1 patients. Recently, several PKD1 patients with a severe renal cystic phenotype due to a seco

  19. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia

    NARCIS (Netherlands)

    Hardies, Katia; de Kovel, Carolien G F; Weckhuysen, Sarah; Asselbergh, Bob; Geuens, Thomas; Deconinck, Tine; Azmi, Abdelkrim; May, Patrick; Brilstra, Eva; Becker, Felicitas; Barisic, Nina; Craiu, Dana; Braun, Kees P J; Lal, Dennis; Thiele, Holger; Schubert, Julian; Weber, Yvonne; van 't Slot, Ruben; Nürnberg, Peter; Balling, Rudi; Timmerman, Vincent; Lerche, Holger; Maudsley, Stuart; Helbig, Ingo; Suls, Arvid; Koeleman, Bobby P C; De Jonghe, Peter

    2015-01-01

    The epileptic encephalopathies are a clinically and aetiologically heterogeneous subgroup of epilepsy syndromes. Most epileptic encephalopathies have a genetic cause and patients are often found to carry a heterozygous de novo mutation in one of the genes associated with the disease entity. Occasion

  20. Generation of a human induced pluripotent stem cell (iPSC line from a patient with family history of diabetes carrying a C18R mutation in the PDX1 gene

    Directory of Open Access Journals (Sweden)

    Xianming Wang

    2016-09-01

    Full Text Available Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor PDX1 leads to pancreatic agenesis, whereas certain heterozygous point mutations are associated with Maturity-Onset Diabetes of the Young 4 (MODY4 and Type 2 Diabetes Mellitus (T2DM. To understand the pathomechanism of MODY4 and T2DM, we have generated iPSCs from a woman with a C18R heterozygous mutation in the transactivation domain of PDX1. The resulting PDX1 C18R iPSCs generated by episomal reprogramming are integration-free, have a normal karyotype and are pluripotent in vitro and in vivo. Taken together, this iPSC line will be useful to study diabetes pathomechanisms.

  1. Genome sequence of a diabetes-prone rodent reveals a mutation hotspot around the ParaHox gene cluster

    DEFF Research Database (Denmark)

    Hargreaves, Adam D.; Zhou, Long; Christensen, Josef

    2017-01-01

    Pdx1 has been grossly affected by GC-biased mutation, leading to the highest divergence observed for this gene across the Bilateria. In addition to genomic insights into restricted caloric intake in a desert species, the discovery of a localized chromosomal region subject to elevated mutation suggests...

  2. Neonatal Jaundice

    DEFF Research Database (Denmark)

    Maimburg, Rikke Damkjær; Væth, Michael; Schendel, Diana

    2008-01-01

    .7]). No associations were found between infantile autism and low Apgar scores, acidosis or hypoglycaemia. Our findings suggest that hyperbilirubinaemia and neurological abnormalities in the neonatal period are important factors to consider when studying causes of infantile autism....

  3. Neonatal Death

    Science.gov (United States)

    ... a premature baby include pneumonia (a lung infection), sepsis (a blood infection) and meningitis (an infection in the fluid around the brain and spinal cord). What birth defects most often cause neonatal death? The most common birth defects that cause ...

  4. 护理干预在新生儿糖尿病合并肺炎中的应用%Application of Nursing Intervention in Neonatal Diabetes Complicated with Pneumonia

    Institute of Scientific and Technical Information of China (English)

    王进文

    2016-01-01

    Objective To explore the application effect of nursing intervention in neonatal diabetes complicated with pneu-monia. Methods Selected 2013 January 2015 December diabetes complicated with pneumonia 166 cases, were randomly di-vided into control group (routine nursing) and observation group (intervention) 83 cases in each, were compared between the two groups hospitalization time and the satisfaction of the parents. Results The length of stay in the observation group was (5.6±2.1)d, the family satisfaction was 98.8%, and the control group was (9.3±2.5)d, and the family satisfaction was 78.3%(P<0.05). Conclusion Application effect of nursing intervention on neonatal diabetes complicated with pneumonia.%目的:探讨护理干预在新生儿糖尿病合并肺炎中的应用效果。方法选取2013年1月-2015年12月收治的糖尿病合并肺炎患儿166例,随机分成对照组(常规护理)和观察组(护理干预)各83例,比较两组住院时间和患儿家属满意度。结果观察组住院时间为(5.6±2.1)d,患儿家属满意度为98.8%,对照组住院时间为(9.3±2.5)d,患儿家属满意度为78.3%(P<0.05)。结论护理干预在新生儿糖尿病合并肺炎中的应用效果满意。

  5. The Effect of Comprehensive Nursing on Neonatal Diabetes with Diarrhea%综合护理对新生儿糖尿病合并腹泻的效果分析

    Institute of Scientific and Technical Information of China (English)

    王进文

    2016-01-01

    Objective To explore the effect of comprehensive nursing on neonatal diabetes with diarrhea. Methods Decem-ber December 2013 to 2015 in Changchun children's hospital out-patient - diagnosis, who were hospitalized in the Depart-ment of diabetic diarrhea with 186 cases of children with selected, were randomly divided into control group (routine nurs-ing) and observation group (Comprehensive Nursing) 93 cases, compared with the treatment effect and the satisfaction of the parents. Results The efficiency of the observation group was 98.9%, the family satisfaction was 100%, the control group was 80.6%, the family satisfaction was 75.3% (P<0.05). Conclusion The effect of comprehensive nursing on neonatal diabetes with diarrhea.%目的:探讨综合护理对新生儿糖尿病合并腹泻的效果。方法选取2013年12月—2015年12月长春市儿童医院门诊-分诊科收治的糖尿病合并腹泻患儿186例,随机分成对照组(常规护理)和观察组(综合护理)各93例,比较治疗效果和患儿家属满意度。结果观察组有效率为98.9%,患儿家属满意度为100%,对照组有效率为80.6%,患儿家属满意度为75.3%(P<0.05)。结论综合护理对新生儿糖尿病合并腹泻的效果满意。

  6. A family with a novel termination mutation in hepatic nuclear factor 1α in maturity-onset diabetes of the young type 3 which is unresponsive to sulphonylurea therapy.

    Science.gov (United States)

    Demol, S; Lebenthal, Y; Bar-Meisels, M; Phillip, M; Gat-Yablonski, G; Gozlan, Y

    2014-01-01

    Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus. To identify the genetic basis in a family with 3 generations of diabetes and to assess the concordance between the genotype and phenotype. A molecular analysis was performed on genomic DNA using polymerase chain reaction, denaturing gradient gel electrophoresis, and sequencing. A mixed-meal tolerance test (MMTT) was performed with/without glibenclamide. Abdominal ultrasonography was performed on all family members with diabetes due to the location of the mutation. A novel c.618G>A, p.W206X termination mutation was identified in the hepatic nuclear factor 1α (HNF1α) gene. The mutation was identified in the proband and 8 of the 14 family members tested. An MMTT stimulus (±2.5 and 5 mg glibenclamide) produced a similar glucose profile and C-peptide graph in both the obese proband and her nonobese mother, showing no effect of the glibenclamide. No evidence of liver adenomas was found in the abdominal ultrasonography. We described a novel c.618G>A, p.W206X mutation in HNF1α associated with MODY 3 but not with hepatocellular adenoma. In contradistinction to most MODY 3 mutations, treatment with sulphonylurea was found to be a clinically ineffective alternative to insulin therapy.

  7. Observation on Neurological Behaviour Development of Neonates with Diabetic Mother in Pragnancy.%妊娠糖尿病母亲所生新生儿神经行为发育观察

    Institute of Scientific and Technical Information of China (English)

    吴育群; 宋燕燕; 邹红梅; 李智华; 赵吉吉

    2001-01-01

    【Objective】 To understand the effect of pregnancy disbetes on neurological behaviour development of neonate for finding out abnormality and exactly intervening. 【Methods】 20 items of Neonatal Behavioral Neurological Assessment(NBNA) was tested in 46 neonates with diabetic mother in pregnancy from January 1995 to December 2000. 【Results】 26.1% of subjects had total NBNA score≤35 at 7th day after birth. There was significant difference in passive muscular tonicity(P<0.05) and great significant difference in active muscular tonicity(P<0.01) of 5 main items of NBNA. There was great significant difference in EEG(P<0.01). 【Conclusions】 We should pay attention to the effect of pregnancy diabetes on neonates. NBNA and EEG could help us find out patients with mild brain damage earlier.This had great significance for bearing and rearing better children.%【目的】为了解妊娠糖尿病对围产新生儿神经行为发育的影响,及早发现问题,以便有针对性地进行干预。【方法】我们于1995年1月~2000年12月对46例妊娠糖尿病母亲所生的新生儿进行了20项神经行为测定(NBNA)。【结果】检测组中有26.1%生后7天NBNA总分≤35分,在NBNA五大项目比较中,被动肌张力有显著性差异(P<0.05),主动肌张力及脑电图检查有非常显著性差异(P<0.01)。【结论】对妊娠糖尿病母亲所生高危新生儿,应重视对新生儿神经行为发育的影响,通过NBNA测定和EEG的检查,能早期发现轻微脑损伤的婴儿,对优生优育有重要意义。

  8. Neonatal neurosonography

    Energy Technology Data Exchange (ETDEWEB)

    Riccabona, Michael, E-mail: michael.riccabona@klinikum-graz.at

    2014-09-15

    Paediatric and particularly neonatal neurosonography still remains a mainstay of imaging the neonatal brain. It can be performed at the bedside without any need for sedation or specific monitoring. There are a number of neurologic conditions that significantly influence morbidity and mortality in neonates and infants related to the brain and the spinal cord; most of them can be addressed by ultrasonography (US). However, with the introduction of first CT and then MRI, neonatal neurosonography is increasingly considered just a basic first line technique that offers only orienting information and does not deliver much relevant information. This is partially caused by inferior US performance – either by restricted availability of modern equipment or by lack of specialized expertise in performing and reading neurosonographic scans. This essay tries to highlight the value and potential of US in the neonatal brain and briefly touching also on the spinal cord imaging. The common pathologies and their US appearance as well as typical indication and applications of neurosonography are listed. The review aims at encouraging paediatric radiologists to reorient there imaging algorithms and skills towards the potential of modern neurosonography, particularly in the view of efficacy, considering growing economic pressure, and the low invasiveness as well as the good availability of US that can easily be repeated any time at the bedside.

  9. Neonatal pain.

    Science.gov (United States)

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback.

  10. Gene-environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure.

    Directory of Open Access Journals (Sweden)

    Hans Bisgaard

    2008-06-01

    Full Text Available BACKGROUND: Loss-of-function variants in the gene encoding filaggrin (FLG are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites in relation to the development of eczema. METHODS AND FINDINGS: We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379, FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27-4.00, p = 0.005, with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79-32.60, p < 0.0001; dog exposure was moderately protective (HR 0.49, 95% CI 0.24-1.01, p = 0.05, but not related to FLG genotype. In Manchester (n = 503 an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13-3.36, p = 0.02. In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35-10.81, p = 0.01, with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16-2.20, p = 0.43. Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation. CONCLUSIONS: We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4 and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially

  11. Ictericia Neonatal

    OpenAIRE

    Blanco de la Fuente, María Isabel

    2014-01-01

    El motivo que ha llevado a la realización de este trabajo fin de grado sobre el tema de la ICTERICIA NEONATAL se debe a la elevada frecuencia de su aparición en la población. Un porcentaje elevado de RN la padecen al nacer siendo, en la mayor parte de los casos, un proceso fisiológico resuelto con facilidad debido a una inmadurez del sistema hepático y a una hiperproducción de bilirrubina. La ictericia neonatal es la pigmentación de color amarillo de la piel y mucosas en ...

  12. Neonatal levels of adiponectin, interleukin-10 and interleukin-12 are associated with the risk of developing type 1 diabetes in childhood and adolescence: A nationwide Danish case-control study.

    Science.gov (United States)

    Thorsen, Steffen U; Pipper, Christian B; Eising, Stefanie; Skogstrand, Kristin; Hougaard, David M; Svensson, Jannet; Pociot, Flemming

    2017-01-01

    An in-depth understanding of the early phase of type 1 diabetes (T1D) pathogenesis is important for targeting primary prevention. We examined if 14 preselected mediators of immune responses differed in neonates that later developed T1D compared to control neonates. The study is a case-control study with a 1:2 matching. The individuals were born between 1981 through 2002. Cases were validated using the National Patient Register and the Danish Childhood Diabetes Register. Interleukin(IL)-1β, IL-4, IL-6, IL-8, IL-10, IL-12p70, interferon gamma, tumor necrosis factor alpha, transforming growth factor beta 1 (active form), leptin, adiponectin, c-reactive protein, mannose-binding lectin and soluble triggering receptor expressed on myeloid cells-1 were measured by using a flowmetric Luminex xMAP® technology. We tested two models both including a number of possible confounders. In the first model (model 1) we also adjusted for HLA-DQB1 genotype. A total of 1930 groups of assay-matched cases and controls (4746 individuals) were included in the statistical analyses. Adiponectin was negatively associated with later risk of T1D in both models (relative change (RC), model 1: 0.95, P=0.046 and model 2: 0.95, P=0.006). IL-10 and IL-12 were both positively associated with T1D risk in the model 2 (RC, 1.19, P=0.006 and 1.07, P=0.02, respectively)-these results were borderline significant in model 1, but showed the same direction as the results from model 2. Our results indicate that specific immunological signatures are already present at time of birth in children developing T1D before the age of 18years. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Neonatal oral administration of DiaPep277, combined with hydrolysed casein diet, protects against Type 1 diabetes in BB-DP rats. An experimental study

    NARCIS (Netherlands)

    Brugman, S; Klatter, FA; Visser, J; Bos, NA; Elias, D; Rozing, J

    Aims/hypothesis. Environmental factors such as diet and bacterial antigens play an important role in the onset of Type 1 diabetes. Different self-antigens are suggested to play a role in the development of diabetes. Antibodies against the 60-kDa heat shock protein 60, which have a high homology to

  14. Neonatal oral administration of DiaPep277, combined with hydrolysed casein diet, protects against Type 1 diabetes in BB-DP rats. An experimental study

    NARCIS (Netherlands)

    Brugman, S; Klatter, FA; Visser, J; Bos, NA; Elias, D; Rozing, J

    2004-01-01

    Aims/hypothesis. Environmental factors such as diet and bacterial antigens play an important role in the onset of Type 1 diabetes. Different self-antigens are suggested to play a role in the development of diabetes. Antibodies against the 60-kDa heat shock protein 60, which have a high homology to b

  15. Neonatal hematology.

    Science.gov (United States)

    Diaz-Miron, Jose; Miller, Jacob; Vogel, Adam M

    2013-11-01

    Neonatal hematology is a complex and dynamic process in the pediatric population. Surgeons frequently encounter hematologic issues regarding hemostasis, inflammation, and wound healing. This publication provides a surgeon-directed review of hematopoiesis in the newborn, as well as an overview of the current understanding of their hemostatic profile under normal and pathologic conditions. © 2013 Published by Elsevier Inc.

  16. Neonatal Kraniefraktur

    DEFF Research Database (Denmark)

    Johannesen, Katrine Marie Harries; Stantchev, Hristo

    2015-01-01

    During the latest decades the incidence of birth traumas has decreased significantly. Even so the traumas still contribute to an increased mortality and morbidity. We present a case of spontaneous neonatal skull fracture following a normal vaginal delivery. Abnormal facial structure was seen...

  17. Mutation analysis of suppressor of cytokine signalling 3, a candidate gene in Type 1 diabetes and insulin sensitivity

    DEFF Research Database (Denmark)

    Gylvin, T; Nolsøe, R; Hansen, T;

    2004-01-01

    Beta cell loss in Type 1 and Type 2 diabetes mellitus may result from apoptosis and necrosis induced by inflammatory mediators. The suppressor of cytokine signalling (SOCS)-3 is a natural inhibitor of cytokine signalling and also influences insulin signalling. SOCS3 could therefore be a candidate...

  18. Pyridoxal phosphate-dependent neonatal epileptic encephalopathy.

    Science.gov (United States)

    Bagci, S; Zschocke, J; Hoffmann, G F; Bast, T; Klepper, J; Müller, A; Heep, A; Bartmann, P; Franz, A R

    2008-03-01

    Pyridox(am)ine-5'-phosphate oxidase converts pyridoxine phosphate and pyridoxamine phosphate to pyridoxal phosphate, a cofactor in many metabolic reactions, including neurotransmitter synthesis. A family with a mutation in the pyridox(am)ine-5'-phosphate oxidase gene presenting with neonatal seizures unresponsive to pyridoxine and anticonvulsant treatment but responsive to pyridoxal phosphate is described. Pyridoxal phosphate should be considered in neonatal epileptic encephalopathy unresponsive to pyridoxine.

  19. Pyridoxal phosphate-dependent neonatal epileptic encephalopathy

    OpenAIRE

    2009-01-01

    Pyridox(am)ine-5′-phosphate oxidase converts pyridoxine phosphate and pyridoxamine phosphate to pyridoxal phosphate, a cofactor in many metabolic reactions, including neurotransmitter synthesis. A family with a mutation in the pyridox(am)ine-5′-phosphate oxidase gene presenting with neonatal seizures unresponsive to pyridoxine and anticonvulsant treatment but responsive to pyridoxal phosphate is described. Pyridoxal phosphate should be considered in neonatal epileptic encephalopathy unrespons...

  20. Precision diabetes: learning from monogenic diabetes.

    Science.gov (United States)

    Hattersley, Andrew T; Patel, Kashyap A

    2017-05-01

    The precision medicine approach of tailoring treatment to the individual characteristics of each patient or subgroup has been a great success in monogenic diabetes subtypes, MODY and neonatal diabetes. This review examines what has led to the success of a precision medicine approach in monogenic diabetes (precision diabetes) and outlines possible implications for type 2 diabetes. For monogenic diabetes, the molecular genetics can define discrete aetiological subtypes that have profound implications on diabetes treatment and can predict future development of associated clinical features, allowing early preventative or supportive treatment. In contrast, type 2 diabetes has overlapping polygenic susceptibility and underlying aetiologies, making it difficult to define discrete clinical subtypes with a dramatic implication for treatment. The implementation of precision medicine in neonatal diabetes was simple and rapid as it was based on single clinical criteria (diagnosed precision diabetes approach in type 2 diabetes will require simple, quick, easily accessible stratification that is based on a combination of routine clinical data, rather than relying on newer technologies. Analysing existing clinical data from routine clinical practice and trials may provide early success for precision medicine in type 2 diabetes.

  1. A possible association between a dysfunctional skin barrier (filaggrin null-mutation status) and diabetes: a cross-sectional study

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Linneberg, Allan; Carlsen, Berit C;

    2011-01-01

    Background Filaggrin proteins are located in the skin and prevent epidermal water loss and impede the entry of micro-organisms, allergens and chemicals. Filaggrin null mutations are strongly associated with ichthyosis vulgaris and atopic dermatitis. Objective The authors aimed to investigate...

  2. Diabetes mellitus caused by mutations in human insulin: analysis of impaired receptor binding of insulins Wakayama, Los Angeles and Chicago using pharmacoinformatics.

    Science.gov (United States)

    Islam, Md Ataul; Bhayye, Sagar; Adeniyi, Adebayo A; Soliman, Mahmoud E S; Pillay, Tahir S

    2017-03-01

    Several naturally occuring mutations in the human insulin gene are associated with diabetes mellitus. The three known mutant molecules, Wakayama, Los Angeles and Chicago were evaluated using molecular docking and molecular dynamics (MD) to analyse mechanisms of deprived binding affinity for insulin receptor (IR). Insulin Wakayama, is a variant in which valine at position A3 is substituted by leucine, while in insulin Los Angeles and Chicago, phenylalanine at positions B24 and B25 is replaced by serine and leucine, respectively. These mutations show radical changes in binding affinity for IR. The ZDOCK server was used for molecular docking, while AMBER 14 was used for the MD study. The published crystal structure of IR bound to natural insulin was also used for MD. The binding interactions and MD trajectories clearly explained the critical factors for deprived binding to the IR. The surface area around position A3 was increased when valine was substituted by leucine, while at positions B24 and B25 aromatic amino acid phenylalanine replaced by non-aromatic serine and leucine might be responsible for fewer binding interactions at the binding site of IR that leads to instability of the complex. In the MD simulation, the normal mode analysis, rmsd trajectories and prediction of fluctuation indicated instability of complexes with mutant insulin in order of insulin native insulin insulin Chicago insulin Los Angeles insulin Wakayama molecules which corresponds to the biological evidence of the differing affinities of the mutant insulins for the IR.

  3. Neonatal infectious diseases: evaluation of neonatal sepsis.

    Science.gov (United States)

    Camacho-Gonzalez, Andres; Spearman, Paul W; Stoll, Barbara J

    2013-04-01

    Neonatal sepsis remains a feared cause of morbidity and mortality in the neonatal period. Maternal, neonatal, and environmental factors are associated with risk of infection, and a combination of prevention strategies, judicious neonatal evaluation, and early initiation of therapy are required to prevent adverse outcomes. This article reviews recent trends in epidemiology and provides an update on risk factors, diagnostic methods, and management of neonatal sepsis. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Effects of streptozotocin-induced type 1 maternal diabetes on PI3K/AKT signaling pathway in the hippocampus of rat neonates.

    Science.gov (United States)

    Hami, Javad; Kerachian, Mohammad-Amin; Karimi, Razieh; Haghir, Hossein; Sadr-Nabavi, Ariane

    2016-01-01

    Diabetes in pregnancy impairs hippocampus development in offspring, leading to behavioral problems and learning deficits. Phosphatidylinositol 3-kinase/protein kinase B (PKB/Akt) signaling pathway plays a pivotal role in the regulation of neuronal proliferation, survival and death. The present study was designed to examine the effects of maternal diabetes on PKB/Akt expression and phosphorylation in the developing rat hippocampus. Wistar female rats were maintained diabetic from a week before pregnancy through parturition and male offspring was killed at first postnatal day (P1). The hippocampal expression and phosphorylation level of PKB/Akt, one of the key molecules in PI3K/AKT signaling pathway, was evaluated using real-time polymerase chain reaction (PCR) and western blot analysis. We found a significant bilateral downregulation of AKT1 gene expression in the hippocampus of pups born to diabetic mothers (p diabetic and insulin-treated groups compared with control (p diabetic group. These results represent that diabetes during pregnancy strongly influences the regulation of PKB/AKT in the developing rat hippocampus. Furthermore, although the control of glycemia by insulin administration is not sufficient to prevent the alterations in PKB/Akt expression, it modulates the phosphorylation process, thus ultimately resulting in a situation comparable to that found in the normal condition.

  5. Resultados gestacionais e neonatais em mulheres com rastreamento positivo para diabetes mellitus e teste oral de tolerância à glicose - 100g normal Gestational and neonatal outcomes in women with positive screening for diabetes mellitus and 100g oral glucose challenge test normal

    Directory of Open Access Journals (Sweden)

    Patricia Moretti Rehder

    2011-02-01

    Full Text Available OBJETIVO: avaliar a frequência de resultados gestacionais e neonatais desfavoráveis em mulheres com rastreamento positivo e diagnóstico negativo para diabetes mellitus gestacional. MÉTODOS: trata-se de um estudo de corte transversal, retrospectivo e descritivo realizado entre 2000 e 2009. Foram incluídas no estudo 409 gestantes com rastreamento positivo para diabetes mellitus. As variáveis estudadas foram: maternas (idade, índice de massa corpórea, antecedente de cesárea, macrossomia ou diabetes mellitus em gestação anterior, antecedente pessoal e familiar de diabetes mellitus e hipertensão arterial crônica e neonatais (poli-hidrâmnio, idade gestacional por ocasião do parto, prematuridade, cesárea, recém-nascido (RN grande para idade gestacional (GIG, macrossomia, índice de Apgar, síndrome do desconforto respiratório, hipoglicemia e hiperbilirrubinemia. Inicialmente foi realizada análise descrita uni e multivariada para a ocorrência de fatores de risco e desfechos neonatais. Foram descritas as prevalências e respectivos intervalos de confiança a 95%. RESULTADOS: em 255 (62,3% das gestantes a via de parto foi cesárea. Quanto aos resultados perinatais, 14,2% dos RN foram classificados como prematuros e 19,3% dos RN como GIG. Os fatores de risco correlacionados com RN GIG foram sobrepeso ou obesidade, idade materna e antecedente de macrossomia em gestação anterior. CONCLUSÕES: na população com fatores de risco positivos ou glicemia de jejum alterada na primeira consulta do pré-natal, mesmo com curva glicêmica normal observa-se taxa de RN GIG elevada assim como índice de cesárea acima dos valores habitualmente presentes nas populações consideradas de baixo risco. As grávidas com tais características constituem um grupo diferenciado.PURPOSE: to determine the prevalence of adverse gestational and neonatal outcomes in women with a positive screening and negative diagnosis for gestational diabetes mellitus (GDM

  6. Effects of different treatment opportunities of patients with gestational diabetes mellitus on maternal and neonatal outcomes%妊娠期糖尿病患者不同治疗时机对母婴预后的影响

    Institute of Scientific and Technical Information of China (English)

    郑智; 吕杰强

    2015-01-01

    Objective: To explore the effects on maternal and infant outcomes of different treatment op-portunities of patients with gestational diabetes mellitus and provide references for clinical treatments.Methods:From August 2013 to August 2014, 276 cases of patients with gestational diabetes mellitus in Wenzhou People’s Hospital were analyzed retrospectively. Patients diagnosed and treated before 32 pregnancy weeks were set as group A, while the rest patients conifrmed and treated at 32 pregnancy weeks and later were enrolled into group B. The patients’ pregnancy outcomes were compared between two groups.Results: The occurrences of patients’ and perinatals’ complications in group A were much lower than group B (P<0.05); the neonatal body masses and gestational ages in group A were signiifcantly better than those in group B, the differences are statistically signiif-cant (P<0.05).Conclusion: For patients with gestational diabetics mellitus, maternal and neonatal outcomes are related to the treatment opportunities, and detection before 32 pregnancy weeks and standardized treatment can effectively control and reduce the occurrences of adverse maternal and infant pregnancy outcomes.%目的:研究妊娠期糖尿病患者不同治疗时机对母婴预后的影响,为临床治疗提供参考和借鉴。方法:回顾性分析2013年8月至2014年8月来温州市人民医院就诊的276例妊娠期糖尿病患者,将在孕32周前确诊并予以治疗的患者设为A组,孕32周及以后确诊并予以治疗的患者设为B组,比较2组患者的妊娠结局。结果:A组患者并发症的发生率、A组围生儿的并发症发生率明显低于B组(P<0.05);A组新生儿的体质量和胎龄明显优于B组,差异均有统计学意义(P<0.05)。结论:妊娠期糖尿病患者的治疗时机关系着母婴的预后,32周之前发现并规范治疗能有效控制并降低母婴不良妊娠结局的发生。

  7. Neonatal Kraniefraktur

    DEFF Research Database (Denmark)

    Johannesen, Katrine Marie Harries; Stantchev, Hristo

    2015-01-01

    During the latest decades the incidence of birth traumas has decreased significantly. Even so the traumas still contribute to an increased mortality and morbidity. We present a case of spontaneous neonatal skull fracture following a normal vaginal delivery. Abnormal facial structure was seen......, and the fracture was identified with an MRI. The fractures healed without neurosurgical intervention. Case reports show that even in uncomplicated vaginal deliveries skull fractures can be seen and should be suspected in children with facial abnormalities....

  8. Novel GATA6 mutations in patients with pancreatic agenesis and congenital heart malformations.

    Directory of Open Access Journals (Sweden)

    Christina S Chao

    Full Text Available Patients with pancreatic agenesis are born without a pancreas, causing permanent neonatal diabetes and pancreatic enzyme insufficiency. These patients require insulin and enzyme replacement therapy to survive, grow, and maintain normal blood glucose levels. Pancreatic agenesis is an uncommon condition but high-throughput sequencing methods provide a rare opportunity to identify critical genes that are necessary for human pancreas development. Here we present the clinical history, evaluation, and the genetic and molecular analysis from two patients with pancreatic agenesis. Both patients were born with intrauterine growth restriction, minor heart defects and neonatal diabetes. In both cases, pancreatic agenesis was confirmed by imaging studies. The patients are clinically stable with pancreatic enzymes and insulin therapy. In order identify the etiology for their disease, we performed whole exome sequencing on both patients. For each proband we identified a de novo heterozygous mutation in the GATA6 gene. GATA6 is a homeobox containing transcription factor involved in both early development of the pancreas and heart. In vitro functional analysis of one of the variants revealed that the mutation creates a premature stop codon in the coding sequence resulting in the production of a truncated protein with loss of activity. These results show how genetic mutations in GATA6 may lead to functional inactivity and pancreatic agenesis in humans.

  9. Mutations in PTF1A cause pancreatic and cerebellar agenesis

    NARCIS (Netherlands)

    Sellick, GS; Barker, KT; Stolte-Dijkstra, [No Value; Fleischmann, C; Coleman, RJ; Garrett, C; Gloyn, AL; Edghill, EL; Hattersley, AT; Wellauer, PK; Goodwin, G; Houlston, RS

    2004-01-01

    Individuals with permanent neonatal diabetes mellitus usually present within the first three months of life and require insulin treatment(1,2). We recently identified a locus on chromosome 10p13-p12.1 involved in permanent neonatal diabetes mellitus associated with pancreatic and cerebellar agenesis

  10. Neonatal Listeriosis

    Directory of Open Access Journals (Sweden)

    Shih-Yu Chen

    2007-01-01

    Full Text Available In Western developed countries, Listeria monocytogenes is not an uncommon pathogen in neonates. However, neonatal listeriosis has rarely been reported in Taiwan. We describe two cases collected from a single medical institute between 1990 and 2005. Case 1 was a male premature baby weighing 1558 g with a gestational age of 31 weeks whose mother had fever with chills 3 days prior to delivery. Generalized maculopapular rash was found after delivery and subtle seizure developed. Both blood and cerebrospinal fluid culture collected on the 1st day yielded L. monocytogenes. In addition, he had ventriculitis complicated with hydrocephalus. Neurologic development was normal over 1 year of follow-up after ventriculoperitoneal shunt operation. Case 2 was a 28-weeks' gestation male premature baby weighing 1180 g. Endotracheal intubation and ventilator support were provided after delivery due to respiratory distress. Blood culture yielded L. monocyto-genes. Cerebrospinal fluid showed pleocytosis but the culture was negative. Brain ultrasonography showed ventriculitis. Sudden deterioration with cyanosis and bradycardia developed on the 8th day and he died on the same day. Neonatal listeriosis is uncommon in Taiwan, but has significant mortality and morbidity. Early diagnosis of perinatal infection relies on high index of suspicion in perinatal health care professionals. [J Formos Med Assoc 2007;106(2:161-164

  11. First 2 cases with thiamine-responsive megaloblastic anemia in the Czech Republic, a rare form of monogenic diabetes mellitus: a novel mutation in the thiamine transporter SLC19A2 gene-intron 1 mutation c.204+2T>G.

    Science.gov (United States)

    Pomahačová, Renata; Zamboryová, Jana; Sýkora, Josef; Paterová, Petra; Fiklík, Karel; Votava, Tomáš; Černá, Zdeňka; Jehlička, Petr; Lád, Václav; Šubrt, Ivan; Dort, Jiří; Dortová, Eva

    2016-12-22

    Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by mutations in the SLC19A2 gene. To date at least 43 mutations have been reported for the gene encoding a plasma membrane thiamine transporter protein (THTR-1). TRMA has been reported in less than 80 cases worldwide. Here, we illustrate 2 female patients with TRMA first diagnosed in the Czech Republic and in central Europe being confirmed by sequencing of the THTR-1 gene SLC19A2. Both subjects are compound heterozygotes with 3 different mutations in the SLC19A2 gene. In case 2, the SLC19A2 intron 1 mutation c.204+2T>G has never been reported before. TRMA subjects are at risk of diabetic ketoacidosis during intercurrent disease and arrythmias. Thiamine supplementation has prevented hematological disorders over a few years in both pediatric subjects, and improved glycaemic control of diabetes mellitus. Patient 1 was suffering from hearing loss and rod-cone dystrophy at the time of diagnosis, however, she was unresponsive to thiamine substitution. Our patient 2 developed the hearing loss despite the early thiamine substitution, however no visual disorder had developed. The novel mutation described here extends the list of SLC19A2 mutations causing TRMA. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Neonatal pulmonary artery thrombosis

    Directory of Open Access Journals (Sweden)

    Mangesh Jadhav

    2012-01-01

    Full Text Available Pulmonary artery thrombosis in neonates is a rare entity. We describe two neonates with this diagnosis; their presentation, evaluation, and management. These cases highlight the importance of this differential diagnosis when evaluating the cyanotic neonate.

  13. Neonatal circumcision.

    Science.gov (United States)

    Lerman, S E; Liao, J C

    2001-12-01

    The merits of neonatal circumcision continue to be debated hotly. Some argue that circumcision is a "uniquely American medical enigma." Most of the world's male population remains uncircumcised; however, most boys born in the United States continue to undergo neonatal circumcision. Review of existing literature supports that most children who are uncircumcised do well from a medical standpoint and, thus, the question of whether US health care practitioners are subjecting neonates to an unnecessary surgical procedure remains. The medical benefits of circumcision are multiple, but most are small. The clearest medical benefit of circumcision is the relative reduction in the risk for a UTI, especially in early infancy. Although this risk [figure: see text] is real, the absolute numbers are small (risk ranges from 1 in 100 to 1 in 1000), and one investigator has estimated that it may take approximately 80 neonatal circumcisions to prevent one UTI. In the case of a patient with known urologic abnormalities that predispose to UTI, neonatal circumcision has a clearer role in terms of medical benefit to the patient. Most of the other medical benefits of circumcision probably can be realized without circumcision as long as access to clean water and proper penile hygiene are achieved. Proper penile hygiene should all but eliminate the risk for foreskin-related medical problems that will require circumcision. Moreover, proper hygiene and access to clean water has been shown to reduce the rate of development of squamous cell carcinoma of the penis in the uncircumcised population. Proper techniques on the care of the foreskin are illustrated in the American Academy of Pediatrics pamphlet titled "How to care for the uncircumcised penis." Regarding the relationship between STDs and circumcision, patient education and the practice of low-risk sexual behavior make a far greater impact than does routine circumcision in hopes of reducing the spread of HIV and other STDs. Nevertheless

  14. The expanding clinical phenotype of the tRNA{sup Leu(UUR)} A{r_arrow}G mutation at np 3243 of mitochondrial DNA: Diabetic embryopathy associated with mitochondrial cytopathy

    Energy Technology Data Exchange (ETDEWEB)

    Feigenbaum, A.; Chitayat, D.; Robinson, B.; MacGregor, D.; Myint, T. [Univ. of Toronto, Ontario (Canada)] [and others

    1996-04-24

    We describe a family which demonstrates and expands the extreme clinical variability now known to be associated with the A{r_arrow}G transition at nucleotide position 3243 of the mitochondrial DNA. The propositus presented at birth with clinical manifestations consistent with diabetic embryopathy including anal atresia, caudal dysgenesis, and multicystic dysplastic kidneys. His co-twin was normal at birth, but at 3 months of life, presented with intractable seizures later associated with developmental delay. The twins` mother developed diabetes mellitus type I at the age of 20 years and gastrointestinal problems at 22 years. Since age 19 years, the maternal aunt has had recurrent strokes, seizures, mental deterioration and deafness, later diagnosed as MELAS syndrome due to the tRNA{sup Leu(UUR)} A{r_arrow}G mutation. A maternal uncle had diabetes mellitus type I, deafness, and normal intellect, and died at 35 years after recurrent strokes. This pedigree expands the known clinical phenotype associated with tRNA{sup Leu(UUR)} A{r_arrow}G mutation and raises the possibility that, in some cases, diabetic embryopathy may be due to a mitochondrial cytopathy that affects both the mother`s pancreas (and results in diabetes mellitus and the metabolic dysfunction associated with it) and the embryonic/fetal and placental tissues which make the embryo more vulnerable to this insult. 33 refs., 1 tab.

  15. Mutations in PCBD1 Cause Hypomagnesemia and Renal Magnesium Wasting

    NARCIS (Netherlands)

    Ferre, S.; Baaij, J.H.F. de; Ferreira, P.; Germann, R.; Klerk, J.B. De; Lavrijsen, M.; Zeeland, F. van; Venselaar, H.; Kluijtmans, L.A.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2014-01-01

    Mutations in PCBD1 are causative for transient neonatal hyperphenylalaninemia and primapterinuria (HPABH4D). Until now, HPABH4D has been regarded as a transient and benign neonatal syndrome without complications in adulthood. In our study of three adult patients with homozygous mutations in the PCBD

  16. Peripartum management of diabetes

    OpenAIRE

    Pramila Kalra; Manjunath Anakal

    2013-01-01

    The peripartum control of diabetes is very important for the well-being of the newborn as higher incidence of neonatal hypoglycemia is seen if maternal hyperglycemia happens during this period. Type of diabetes (type 1, type 2 or gestational diabetes) also has an effect on the glucose concentration during intrapartum period. During the latent phase of labor, the metabolic demands are stable but during active labor there is increased metabolic demand and decreased insulin requirement. After de...

  17. AB096. Pharmaco-genetic guided personalized medicine: discovery of a maturity onset diabetes of the young (MODY2) novel mutation [S441W in glucose kinase (GCK) gene] by next generation sequencing (NGS)

    Science.gov (United States)

    Clara, Tan Si Hua; Fen, Ang Su; Jessie, Fong Choi Wan; Ester, Yeoh Chai Kheng; Subramaniam, Tavintharan; Fang, Sum Chee; Chi, Lim Su

    2015-01-01

    Background and objective Monogenic diabetes or maturity onset diabetes of the young (MODY) is characterized by young-onset (G, p.Ser441Trp) in the GCK gene, which was confirmed by bi-directional Sanger’s sequencing. The mutation is predicted to be functionally deleterious using multiple bioinformatics tools (e.g., SIFT and PolyPhen-2). In accordance with clinical practice guideline, insulin replacement was successfully discontinued with no deterioration of glycemic control. Conclusions The successful treatment-conversion based on genotype exemplifies how pharmaco-genetics can improve disease-stratify to inform diagnosis and treatment. This can translate into improved clinical outcome and quality of life.

  18. Clinical significance of large-scale screening of A1555G mutation of mitochondria DNA for neonates%线粒体DNA A1555G突变在新生儿大规模筛查的临床意义

    Institute of Scientific and Technical Information of China (English)

    蔡筠; 罗彩群; 谢建生; 吴维青; 耿茜; 徐志勇; 郝颖; 徐晓昕

    2011-01-01

    目的 探讨在新生儿中进行线粒体DNA(mitochondria DNA,mtDNA)A1555G突变基因大规模筛查在预防药物性耳聋的必要性.方法 随机取2008年在深圳市出生的1000名新生儿的血滤纸标本,用Chelex-100树脂提取DNA,PCR扩增,变性高效液相色谱法(denaturing hig-performance liquid chromatography,DHPLC)进行mtDNA A1555G突变基因筛查,计算出阳性突变频率.结果 1000名新生儿血滤纸样本中,共检测出2例样本存在mtDNA A1555G突变,突变率为0.2%.结论 mtDNA A1555G突变在新生儿中出现的频率较高,对其进行mtDNA A1555G突变大规模筛查发现氨基甙类抗生素敏感个体,能有效地对新生儿及其家族高危人群进行合理性指导用药,从而更好地预防药物性耳聋.%Objective To explore the necessity of large-scale screening of mitochondria DNA (mtDNA) A1555G mutation for prevention of aminoglycoside antibiotic induced deafness in newborns.Methods One thousand blood filter samples were collected from neonates born in July 2008 in Shenzhen.DNA was extracted with Chelex-100 Resin and amplified by PCR. The mtDNA A1555G mutation was determined by denaturing high-performance liquid chromatography (DHPLC) for PCR products. The positive frequency was calculated. Results The mitochondrial DNA A1555G mutation was detected in 2 cases of 1000 neonates. The frequency of mutation was 0. 2%. Conclusion There is a high frequency of mtDNAA1555G mutation in neonates, the large-scale screening of mtDNAA1555G mutation in newborns might detect the individuals sensitive to aminoglycoside antibiotic, which is helpful to guide a rational medication for newborns and the maternal relatives at high-risk. Furthermore, it might be useful to prevent aminoglycoside antibiotic induced deafness.

  19. Genomet og diabetes

    DEFF Research Database (Denmark)

    Allin, Kristine Højgaard; Hansen, Torben; Pedersen, Oluf Borbye

    2014-01-01

    In terms of their genetic architecture monogenic diabetes and type 2 diabetes represent two extremes. Whereas each subtype of monogenic diabetes is caused by one penetrant, rare mutation in a single gene, the genetic susceptibility to type 2 diabetes can be attributed to many low-penetrant variants...... across the genome. At present, only 10% of the genetic susceptibility to type 2 diabetes can be explained by the hitherto identified 90 genomic loci. Here we briefly review the genetics of monogenic diabetes and type 2 diabetes and outline future directions of research within this field....

  20. study between visfatin and gestational diabetes and neonatal weight%内脂素与妊娠期糖尿病及新生儿体重相关性研究

    Institute of Scientific and Technical Information of China (English)

    田海霞; 姚保芬

    2012-01-01

    目的 通过对糖尿病和非糖尿病孕妇血清、胎盘内脂素mRNA表达的检测,探讨内脂素与妊娠期糖尿病及新生儿体重之间的关系.方法 选择2008年1月至2012年1月在定州市妇幼保健院妇产科住院的孕妇,根据妊娠期血糖值将130名研究对象分为糖尿病组和非糖尿病组.采用酶联免疫法检测血清内脂素,采用逆转录聚合酶链反应检测血清及胎盘内脂素mRNA的表达水平,并进行分析.结果 ①糖尿病组和非糖尿病组低密度脂蛋白、空腹血糖、胰岛素抵抗指数差异有统计学意义(t值分别为2.59、3.06、2.71,均P<0.05);②糖尿病组和非糖尿病组胎盘内脂素mRNA表达水平差异有统计学意义(t=2.35,P<0.05);③胎盘内脂素mRNA表达与低密度脂蛋白负相关(r=-0.34,P<0.05),与胰岛素抵抗指数、空腹血糖正相关(r值分别为0.43、0.46,均P<0.05);④新生儿体重与胎盘内脂素mRNA表达水平正相关(r=0.37,P<0.05).结论 胎盘内脂素表达增高促进胎儿的生长发育,新生儿体重与胎盘内脂素的表达正相关.%Objective To detect the correlation between visfatin and gestational diabetes and neonatal weight by exploring the expression of serum and placental visfatin mRNA in diabetic and non-diabetic pregnant women. Methods 130 subjects were from patients hospitalized in department of obstetrics and gynecology of Maternal and Child Health Hospital of Dingzhou from January 2008 to January 2012. According to blood glucose level during pregnancy, the subjects were divided into diabetic group and non-diabetic group. The serum visfatin was detected by ELISA method and the visfatin mRNA expression of serum and placenta were measured by RT-PCR method. The data was analyzed. Results The differences in low-density lipoprotein ( LDL ), fasting glucose and insulin resistance index between diabetic group and non-diabetic group were statistically significant ( t value was 2.59, 3.06 and 2.71 respectively, all P

  1. Gestational Diabetes Screening During Pregnancy

    Directory of Open Access Journals (Sweden)

    Cihan Cetin

    2015-09-01

    Full Text Available Gestational diabetes is a type of diabetes that is diagnosed during pregnancy in patients who do not have pregestational diabetes. Unless diagnosed and treated on time, it may cause various maternal, fetal and neonatal complications like macrosomia, polyhydramniosis, preterm labor, in utero ex fetus, infections, neonatal metabolic complications. The diagnosis of gestational diabetes stands on single-step or two-step screening/diagnosis strategies. These screening and diagnosis tests should be well known by physicians who are taking care of pregnants. [Archives Medical Review Journal 2015; 24(3.000: 348-354

  2. The interactive role of type 2 diabetes mellitus and E-selectin S128R mutation on susceptibility to coronary heart disease

    Directory of Open Access Journals (Sweden)

    Mohamed Gamal H

    2007-06-01

    Full Text Available Abstract Background The role of gene-environment interactions as risk factors for coronary heart disease (CAD remains largely undefined. Such interactions may involve gene mutations and disease conditions such as type 2 diabetes mellitus (DM2 predisposing individuals to acquiring the disease. Methods In the present study, we assessed the possible interactive effect of DM2 and E-selectin S128R polymorphism with respect to its predisposing individuals to CAD, using as a study model a population of 1,112 patients and 427 angiographed controls of Saudi origin. E-selectin genotyping was accomplished by polymerase chain reaction (PCR amplification followed by PstI restriction enzyme digestion. Results The results show that DM2 is an independent risk factor for CAD. In the absence of DM2, the presence of the R mutant allele alone is not significantly associated with CAD (p = 0.431, OR 1.28. In contrast, in the presence of DM2 and the S allele, the likelihood of an individual acquiring CAD is significant (odds ratio = 5.44; p = Conclusion Our findings indicate therefore that the risk of acquiring CAD in patients with DM2 increases significantly in the presence of the 128R mutant allele of the E-selectin gene.

  3. Long-term replacement of a mutated nonfunctional CNS gene: reversal of hypothalamic diabetes insipidus using an EIAV-based lentiviral vector expressing arginine vasopressin.

    Science.gov (United States)

    Bienemann, Alison S; Martin-Rendon, Enca; Cosgrave, Anna S; Glover, Colin P J; Wong, Liang-Fong; Kingsman, Susan M; Mitrophanous, Kyriacos A; Mazarakis, Nicholas D; Uney, James B

    2003-05-01

    Due to the complexity of brain function and the difficulty in monitoring alterations in neuronal gene expression, the potential of lentiviral gene therapy vectors to treat disorders of the CNS has been difficult to fully assess. In this study, we have assessed the utility of a third-generation equine infectious anemia virus (EIAV) in the Brattleboro rat model of diabetes insipidus, in which a mutation in the arginine vasopressin (AVP) gene results in the production of nonfunctional mutant AVP precursor protein. Importantly, by using this model it is possible to monitor the success of the gene therapy treatment by noninvasive assays. Injection of an EIAV-CMV-AVP vector into the supraoptic nuclei of the hypothalamus resulted in expression of functional AVP peptide in magnocellular neurons. This was accompanied by a 100% recovery in water homeostasis as assessed by daily water intake, urine production, and urine osmolality lasting for a 1-year measurement period. These data show that a single gene defect leading to a neurological disorder can be corrected with a lentiviral-based strategy. This study highlights the potential of using viral gene therapy for the long-term treatment of disorders of the CNS.

  4. Cardiac function in offspring of women with diabetes using fetal ECG, umbilical cord blood pro-BNP, and neonatal interventricular septal thickness

    DEFF Research Database (Denmark)

    Halse, Karen; Lindegaard, Marie Louise Skakkebæk; Amer-Wahlin, Isis

    2013-01-01

    were included prospectively. Umbilical cord blood pro-BNP concentrations were measured immediately after delivery (n=68) and echocardiography was performed in the newborns (n=75). Fetal ECG in combination with cardiotocography, that is STAN technology was also performed during labor. Results......: The concentration of umbilical cord blood pro-BNP was associated positively with the neonatal cardiac interventricular septal thickness (P=0.025) and associated negatively with umbilical cord blood pH levels (P=0.036). Fetal ECG changes (STAN events) were recorded in 22 of 53 labors where STAN was used (42......%). No correlation was observed between interventricular septal thickness and STAN events. Conclusion: Increased umbilical cord blood pro-BNP is associated with echocardiographic signs of cardiomyopathy and with lower umbilical cord blood pH....

  5. 111例未通过听力筛查新生儿常见耳聋基因突变位点分析%The analysis of common mutation in deafness-associated gene in 111 neonates who failed to pass newborn hearing screening

    Institute of Scientific and Technical Information of China (English)

    张舒; 周杰; 程龙飞; 张其刚; 潘琼

    2016-01-01

    Objective To explore the genetic mutation in neonates who failed to pass hearing screening.Methods A total of 111 cases of neonates who failed to pass hearing screening and were conifrmed sensorineural deafness by auditory brainstem evoked potential (ABR) were randomly selected. The heel blood was collected and DNA was extracted.GJB2, SLC26A4, and 11 mutation hotspots in mitochondria gene12SrRNA were tested. The relationship between degree of hearing loss and gene mutation was analyzed.Results In 111 neonates, mutation in deafness gene were found in 24 cases (21.6%) . Among them 14 cases (12.6%) hadGJB2 gene mutation including 5 cases of 235delC single heterozygous mutation, 5 cases of 235delC, and 1 case each of 299_300delAT compound heterozygous mutation, 235delC homozygous mutation, 299_300delAT single heterozygous mutation, 176_191del16 and 235delC compound heterozygous mutation, and 299_300delAT and 508_511dupAACG compound heterozygous mutation respectively. Ten cases (9.0%) hadSLC26A4 gene mutation including 2 cases of IVS7-2A>G single heterozygous mutation, 3 cases of 1226G>A single heterozygous mutation, 2 cases of 2168A>G single heterozygous mutation, and 3 cases of IVS7-2A>G and 2168A>G compound heterozygous mutation. Mitochondrial gene mutations were not detected. Conclusions Deafness gene mutation is detected in more than 1/5 neonates who failed to pass newborn hearing screening. GJB2 gene mutation is the most commons. The implementation of hotspots deafness gene detection can improve the diagnostic rate of deafness.%目的:了解未通过听力筛查新生儿耳聋基因突变情况。方法随机选取听力筛查未通过、经听觉脑干诱发电位(ABR)测试为感音神经性耳聋患儿111例,收集足跟血血片,提取基因组DNA后,检测GJB 2、SLC 26 A 4和线粒体12SrRNA基因中的11个热点的突变,分析听力损失程度与突变的关联。结果111例新生儿中,共检出携带耳聋基因突变24例(21.6%

  6. Carnitine in neonatal nutrition.

    Science.gov (United States)

    Borum, P R

    1995-11-01

    Experimental evidence from several investigators suggests that carnitine is a conditionally essential nutrient for neonates. If carnitine is a conditionally essential nutrient for the neonate, most neonates on total parenteral nutrition in the United States are not receiving adequate nutritional support. The metabolic functions of carnitine are varied and important in several aspects of neonatal physiology. All neonates receiving breast milk receive dietary carnitine and most neonates receiving enteral infant formulas receive dietary carnitine at a level similar to that of the breast-fed neonate. However, most neonates on total parenteral nutrition receive no dietary carnitine. Investigators have been testing the working hypothesis that carnitine is a conditionally essential nutrient for the neonate for many years. This review discusses (1) data supporting the hypothesis, (2) reasons why it has not been either proved or disproved by now, and (3) the author's view of a prudent approach to dietary carnitine supplementation of neonates.

  7. Neonatal lupus.

    Science.gov (United States)

    Robles, David T; Jaramillo, Lorena; Hornung, Robin L

    2006-12-10

    An otherwise healthy 5-week-old infant with erythematous plaques predominantly on the face and scalp presented to our dermatology clinic. The mother had been diagnosed with lupus erythematosus 2 years earlier but her disease was quiescent. Neonatal lupus is a rare condition associated with transplacental transfer of IgG anti-SSA/Ro and anti-SSB/La antibodies from the mother to the fetus. Active connective tissue disease in the mother does not have to be present and in fact is often absent. Although the cutaneous, hematologic and hepatic manifestations are transient, the potential for permanent heart block makes it necessary for this to be carefully ruled out. As in this case, the dermatologist may be the one to make the diagnosis and should be aware of the clinical presentation, work-up, and management of this important disease.

  8. Somatic hypermutation of immunoglobulin genes in human neonates.

    Science.gov (United States)

    Ridings, J; Nicholson, I C; Goldsworthy, W; Haslam, R; Roberton, D M; Zola, H

    1997-05-01

    The antibody response in the young infant is limited in several ways; in particular, responses generally are of low affinity and restricted to IgM. This raises the question whether the affinity maturation process, consisting of somatic mutation of immunoglobulin genes coupled with selection of high-affinity variants, is operative in the neonate. Re-arranged V(H)6 genes were amplified by polymerase chain reaction (PCR) from cord blood and from peripheral blood of infants. Heteroduplex analysis detected mutation in only 2/18 cord blood samples, while mutations were seen from about 10 days of age onwards. Cloning and sequencing of mutated neonatal V(H)6 genes showed that mutated sequences contained relatively few mutations (one to three mutations per sequence) compared with published values of about 10 in adult IgM sequences. Selection was not evident in the majority of neonatal samples. Thus mutation can occur in the human neonate, but is minimal and generally not accompanied by selection. The age at which affinity maturation develops effectively is yet to be defined.

  9. Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species.

    Science.gov (United States)

    Amaral, Sandra; Oliveira, Paulo J; Ramalho-Santos, João

    2008-02-01

    Diabetes Mellitus (DM), a state of chronic hyperglycemia, is a major cause of serious micro and macrovascular diseases, affecting, therefore, nearly every system in the body. Growing evidence indicates that oxidative stress is increased in diabetes due to overproduction of reactive oxygen species (ROS) and decreased efficiency of antioxidant defences, a process that starts very early and worsens over the course of the disease. During the development of diabetes, oxidation of lipids, proteins and DNA increase with time. Mitochondrial DNA mutations have also been reported in diabetic tissues, suggesting oxidative stress-related mitochondrial damage. Diabetes-related oxidative stress may also be the trigger for many alterations on sexual function, which can also include decreased testicular mitochondrial function. Although sexual disorders have been extensively studied in diabetic men, possible changes in the sexual function of diabetic women have only recently received attention. The prevalence of sexual dysfunction in diabetic men approaches 50%, whereas in diabetic women it seems to be slightly lower. Testicular dysfunction, impotence, decreased fertility potential and retrograde ejaculations are conditions that have been described in diabetic males. Diabetes is also the most common cause of erectile dysfunction in men. Poor semen quality has also been reported in diabetic men, including decreased sperm motility and concentration, abnormal morphology and increased seminal plasma abnormalities. In addition, diabetic men may have decreased serum testosterone due to impaired Leydig cell function. Among diabetic women neuropathy, vascular impairment and psychological complaints have been implicated in the pathogenesis of decreased libido, low arousability, decreased vaginal lubrication, orgasmic dysfunction, and dyspareunia. An association between the production of excess radical oxygen species and disturbed embryogenesis in diabetic pregnancies has also been suggested

  10. Influence of Gestational Diabetes Mellitus in Treatment Time on Prognosis of Maternal and Neonatal%妊娠期糖尿病治疗时机对母婴预后的影响

    Institute of Scientific and Technical Information of China (English)

    李燕

    2015-01-01

    目的:观察妊娠期糖尿病治疗时机对母婴预后的影响。方法2011年01月-2014年10月,在本院就诊并分娩的妊娠期糖尿病患者130例,根据不同的治疗时机分为三组,孕早期组、孕中期组及孕晚期组。孕早期组在孕18周以内、孕中期组在孕18周-32周、孕晚期组在孕32周以后确诊并且进行降糖治疗。对所有患者利用饮食调理、运动指导、个体给药等综合进行治疗,控制患者血糖水平,并且治疗过程中,对各产妇进行孕期监护。检测3组分娩前后血糖,观察孕妇围产并发症及新生儿不良结局发生率。结果3组孕妇在分娩前及分娩后检测血糖,孕晚期组患者血糖水平最高,孕中期组次之,孕早期组患者最低,P<0.05;3组孕妇围产并发症发生率比较,孕晚期患者最高(52.6%),孕中期次之(42.9%),孕早期患者最低(20.9%),P<0.05;3组新生儿不良结局发生率比较,孕晚期组最高(44.7%),孕中期次之(30.6%),孕早期组最低(14.0%),P<0.05。结论妊娠期糖尿病的治疗时机影响妊娠结局,治疗时机越早,干预效果越好,早期干预治疗可有效降低妊娠期糖尿病孕妇及新生儿并发症的发生率,保障母婴健康。%Objective: To observe the influence of diabetes treatment time on prognosis of the period of pregnancy on maternal and neonatal.Methods: FromJanuary2011 to october2014, 130 cases of gestational diabetes patients in the hospital childbirthwere divided into 3 groups:early pregnancy group,the second trimester and late pregnancy group group , according to the different treatment time . Early pregnancy group at 18 weeks of pregnancy, second trimester pregnancy within the group in 18 weeks -32 weeks, late pregnancy group after 32 week pregnancy diagnosed and hypoglycemic treatment. For all patients using diet, exercise guidance, individual administration comprehensive treatment, control of blood glucose

  11. Treatment resistant hyperemesis gravidarum in a patient with type 1 diabetes mellitus: neonatal withdrawal symptoms after successful antiemetic therapy with mirtazapine.

    Science.gov (United States)

    Schwarzer, V; Heep, A; Gembruch, U; Rohde, A

    2008-01-01

    Here we present the case of a 30-year-old woman with type I diabetes mellitus, preeclampsia and treatment resistant persistent hyperemesis gravidarum in her 25th week of gestation who was successfully treated with the antidepressant mirtazapine (Remergil). Nausea and vomiting resolved within 5 days. After discharge from the hospital in 28 weeks of gestation and discontinuation of the medication on her own initiative a relapse occurred, once again with good response to mirtazapine. The drug was continued until birth. At 34 + 0 weeks a cesarean section was performed due to fetal growth restriction and deteriorating preeclampsia. During the second and fourth day postnatal age the child temporarily developed hyperarousal which could be explained by mirtazapine withdrawal.

  12. Maternal vitamin D status in type 1 diabetic pregnancy: impact on neonatal vitamin D status and association with maternal glycaemic control.

    Directory of Open Access Journals (Sweden)

    Sarah E Bennett

    Full Text Available OBJECTIVE: The first aim of this study was to assess 25-hydroxy vitamin D (25OHD concentrations in women with type 1 diabetes (T1DM during pregnancy, post-delivery and also foetal (cord blood 25OHD concentrations and to examine relationships between these. The second aim of the study was to investigate potential interactions between maternal body mass index (BMI and foetal vitamin D status. A further study aim was to examine potential relationships between maternal 25OHD and glycosylated haemoglobin (HbA1c throughout pregnancy. RESEARCH DESIGN AND METHODS: This was an observational study of 52 pregnant controls without diabetes and 65 pregnant women with T1DM in a university teaching hospital. Maternal serum 25OHD was measured serially throughout the pregnancy and post-delivery. Cord blood 25OHD was measured at delivery. 25OHD was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS. RESULTS: Vitamin D deficiency (25OHD 30 kg/m(2 (nmol/L ± SD; 19.93 ± 11.15 vs. 13.73 ± 4.74, p=0.026]. In the T1DM group, HbA1c at booking was significantly negatively correlated with maternal 25OHD at all 3 trimesters (p=0.004; p=0.001; p=0.05. CONCLUSION: In T1DM pregnancy, low vitamin D levels persist throughout gestation and post-delivery. Cord blood vitamin D levels correlate with those of the mother, and are significantly lower in obese women than in their normal weight counterparts. Maternal vitamin D levels exhibit a significant negative relationship with HbA1c levels, supporting a potential role for this vitamin in maintaining glycaemic control.

  13. The DNA ND4 12026 A to G mutation of mitochondria and type 2 diabetes%线粒体DNA ND4 12026基因突变与糖尿病

    Institute of Scientific and Technical Information of China (English)

    秦跃娟; 于永春; 史京衡; 吴松华

    2001-01-01

    目的研究线粒体DNA ND4 12026位点在中国上海地区非肥胖2型糖尿病患者中的突变情况,并探讨该位点突变的临床特征。方法采用PCR-SSCP、PCR-RFLP及PCR产物直接测序等技术检测线粒体DNA、ND4片段的突变情况。结果发现286例糖尿病患者血样中有12例患者mtDNA ND4基因上12026位点存在AtoG的点突变,导致异亮氨酸错义突变成缬氨酸,而在242例非糖尿病对照组个体中仅1例存在同样突变。对该位点突变的临床分析发现起病年龄低,58%有家族史,需要胰岛素治疗。结论12026位点A to G的突变可能与糖尿病的发生有关,并有一定的临床特征。%Objective To investigate the prevalence of mutation at position 12026 of mitochondrial ND4 gene in Chinese diabetes and analyze the clinical characteristics of these patients. Methods Using PCR-SSCP, PCR-RFLP and PCR product direct sequencing technique, we analyzed the mutation of mitochondrial DNA(mtDNA) ND4 gene.Results A to G mutation at position 12026 of mitochondrial DNA ND4 were found in 12 diabetics (12/286) and one in the control subjects, which was resulted from misplacement of isoleucine by valine. The patients with mutation exhibited characteristics of early onset, more family histories(58 % ) and needed insulin therapy more frequently than the patients without the mutation. Conclusion We infer that the mutation at position 12026 is related to the development of diabetes. (Shanghai Med J, 2001,24: 210-213)

  14. Study on the relationship between Gestational diabetes mellitus and neonatal jaundice%妊娠期糖尿病与新生儿黄疸的相关性研究

    Institute of Scientific and Technical Information of China (English)

    田淑新; 杨硕

    2012-01-01

    OBJECTIVE To explore the high risk factors of neonatal jaundice, understand the relationship between gestational diabetes mellitus and neonatal jaundice. METHODS From January 2008 - June 2010, 50 full-term newboms delivered by gestational diabetic pregnant women were collected according to the gestational glucose levels of mother. 25 cases were randomly selected as group A, 25 patients were selected as B group, 25 cases were selected as control group (neonatal by cesarean section at the same period). RESULTS In A group, the bilirubin determination value after 24 hours was (4.3 + 1.8) mg/dl, and bilirubin determination value and its peak after 72h were 72h (9.2 + 1.7) mg/dl and peak (12.3 + 2.1) mg/dl, which were higher than those of group B [bilirubin determination value after 24 hours was (2.9 +1.7) mg/dl, and determination value after 72h and its peak were (7.3 +/-1.5) mg/dl and (10.1 + 1.7) mg/dl, respectively] and C group [bilirubin determination value after 24 hours was (2.7 + 1.6) mg/dl, and determination value after 72h and its peak were (7 + 1.4) mg/dl and (9.3 + 1.4) mg/dl, respectively] (P < 0.05) . The proportion of baby required phototherapy in group A (20%) was significantly higher than that in B group (Wo) and C group (0%)(P< 0.05). CONCLUSION Gestational maternal glucose levels in group A and group B, especially more serious for children with jaundice symptoms. Effective control of blood glucose levels during pregnancy in pregnant women, which can effectively improve the neonatal jaundice.%目的 为探索新生儿黄疸高危因素,了解妊娠期糖尿病与新生儿黄疸的相关性.方法 选择2008年1月~2010年6月某院妊娠期糖尿病母亲所分娩的50例足月新生儿,依据母亲妊娠期血糖水平,随机抽样将其中25例分为A组,余者25例分为B组,对照组25例为C组,为同期剖宫产的正常足月新生儿.结果 A组出生24h后胆红素测定值[(4.3±1.8) mg/dl]、72 h后胆红素测定值[(92±1.7)mg

  15. Routine neonatal circumcision?

    OpenAIRE

    Tran, P. T.; Giacomantonio, M.

    1996-01-01

    Routine neonatal circumcision is still a controversial procedure. This article attempts to clarify some of the advantages and disadvantages of neonatal circumcision. The increased rate of penile cancer among uncircumcised men appears to justify the procedure, but that alone is not sufficient justification. The final decision on neonatal circumcision should be made by parents with balanced counsel from attending physicians.

  16. The Meta-analysis of the Neonatal Safety in Women of Gestational Diabetes Mellitus Who Treated with Metformin%二甲双胍对妊娠糖尿病患者新生儿安全性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    朱斌; 张蕾; 陈瑞玲; 刘腾; 田月; 赵志刚

    2016-01-01

    Objective: To evaluate the neonatal safety of patients with gestational diabetes mellitus treated with metformin.Methods: A search for relevant studies were performed using PubMed(1948-2014), Embase(1974-2014), the Web of knowledge(1950-2014), and the Cochrane database, included all randomized control trials published in English.Results: Eight RCTs (1712 patients with gestational diabetes mellitus) were retrieved; of those 853 patients were given metformin, and 859 patients were given insulin. Use of metformin significantly decreased the risk of neonatal hypoglycemia (RR=0.58, 95%CI [0.43, 0.78],P=0.0003) and admission rates to neonatal intensive care units (RR=0.74, 95%CI [0.61, 0.89], P=0.002). No other adverse effects were observed, such as hyperbilirubinaemia (RR=0.83, 95% CI[0.64, 1.08],P=0.16), large for gestational age (RR=0.85, 95%CI[0.68, 1.05],P=0.14), small for gestational age (RR=0.92, 95%CI [0.61,1.39],P=0.69), macrosomia (RR=0.75, 95%CI [0.54, 1.03], P=0.07 ) or respiratory distress syndrome (RR=0.88, 95%CI [0.55, 1.41],P=0.6).Conclusions: Metformin may be beneficial in treating gestational diabetes. However, even more studies are needed to provide more evidence for the future use of metformin.%目的:通过Meta分析评价二甲双胍治疗妊娠糖尿病对新生儿安全性的影响。方法:网络检索Cochrane Central Register of Controlled Trials(CENTRAL)、Medline、EMBASE、Science Citation Index等数据库,并纳入相关随机对照试验。对纳入文献进行质量评价,数据分析采用RevMan 5.1,对于异质性小的研究合并效应量。结果:共纳入8项随机对照试验,总计1712例受试对象,其中853例患者接受二甲双胍治疗,859例患者接受胰岛素治疗。通过Meta分析发现,二甲双胍与胰岛素治疗组相比,在不良围生期结局(如胎儿死亡、巨大儿、新生儿呼吸窘迫综合征、新生儿黄疸、新生儿入住监护病房、大于胎龄儿、小于胎龄儿)

  17. MIDD or MELAS : that's not the question MIDD evolving into MELAS : a severe phenotype of the m.3243A>G mutation due to paternal co-inheritance of type 2 diabetes and a high heteroplasmy level.

    Science.gov (United States)

    de Wit, H M; Westeneng, H J; van Engelen, B G M; Mudde, A H

    2012-12-01

    Maternally inherited diabetes and deafness (MIDD) and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) are different syndromes, but are caused by the same m.3243A>G mutation in mitochondrial DNA. Why some patients develop MIDD while others MELAS is unknown, but may be related to heteroplasmy level. Progression from MIDD to MELAS has not been described. Here we report a patient with MIDD who over time developed severe insulin resistance and symptoms and signs consistent with MELAS. The most likely explanation here was paternal co-inheritance of type 2 diabetes in combination with a high heteroplasmy level. The present case showing evolution of MIDD to MELAS supports the concept that both syndromes can be regarded as two phenotypes of the same disease.

  18. Severe neonatal Marfan syndrome resulting from a de novo 3-bp insertion into the fibrillin gene on chromosome 15.

    OpenAIRE

    Milewicz, D M; Duvic, M

    1994-01-01

    Severe neonatal Marfan syndrome has features of the Marfan syndrome and congenital contractural arachnodactyly present at birth, along with unique features such as loose, redundant skin and pulmonary emphysema. Since the Marfan syndrome and congenital contractural arachnodactyly are due to mutations in different genes, it has been uncertain whether neonatal Marfan syndrome is due to mutations in the fibrillin gene on chromosome 15 or in another gene. We studied an infant with severe neonatal ...

  19. Cerebral infarction and femoral venous thrombosis detected in a patient with diabetic ketoacidosis and heterozygous factor V Leiden G1691A and PAI-1 4G/5G mutations.

    Science.gov (United States)

    Yaroglu Kazanci, Selcen; Yesilbas, Osman; Ersoy, Melike; Kihtir, Hasan Serdar; Yildirim, Hamdi Murat; Sevketoglu, Esra

    2015-09-01

    Cerebral infarction is one of the serious neurological complications of diabetic ketoacidosis (DKA). Especially in patients who are genetically prone to thrombosis, cerebral infarction may develop due to inflammation, dehydration, and hyperviscocity secondary to DKA. A 6-year-old child with DKA is diagnosed with cerebral infarction after respiratory insufficiency, convulsion, and altered level of consciousness. Femoral and external iliac venous thrombosis also developed in a few hours after central femoral catheter had been inserted. Heterozygous type of factor V Leiden and PAI-14G/5G mutation were detected. In patients with DKA, cerebral infarction may be suspected other than cerebral edema when altered level of consciousness, convulsion, and respiratory insufficiency develop and once cerebral infarction occurs the patients should also be evaluated for factor V Leiden and PAI-14G/5G mutation analysis in addition to the other prothrombotic risk factors.

  20. Identification and diagnosis of three novel mutations in SLC25A13 gene of neonatal intrahepatic cholestasis caused by citrin deficiency%Citrin缺陷导致的新生儿肝内胆汁淤积症SLC25A13基因三个新突变的识别及诊断

    Institute of Scientific and Technical Information of China (English)

    宋元宗; 盛建胜; 牛飼美晴; 胡務亮; 张春花; 小林圭子

    2008-01-01

    Objective Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD, OMIM 605814 ) is a novel autosomal recessive disease results from mutations in the gene SLC25A13 that encodes for citrin, a liver-type aspartate/glutamate cartier located in the mitochondrial inner membrane. Most of the Chinese NICCD patients diagnosed by genetic analysis had the sameSLC25A13 mutations as Japanese, however, in some cases, the known mutations were not detected. This research aimed to identify novel SLC25A13 mutations in Chinese NICCD patients and to explore the experimental conditions for their genetic diagnosis.Methods Genomic DNA was extracted from blood samples of 3 NICCD patients from Taiwan (P757), Guangdong (P1194) and Hebei (P1443) Province of China, respectively; and all the 18 exons and their flanking sequences of SLC25A13 gene were sequenced. Furthermore, the identified novel mutations were diagnosed by amplification with PCR, digestion with corresponding restriction endonuclease, and agarose gel electrophoresis.Results Three novel mutations identified in SLC25A13 gene of the 3 NICCD patients were an abnormal splicing IVS7-2A>G (P757), a missense A541D (c. 1622C > A, P1194) and a nonsense R319X (c. 955C > T, P1443). The PCR-RFLP procedures for their genetic diagnosis were also established, with specific fragments on electrophoresis after digestion of the PCR products with three different restriction endonucleases Msp Ⅰ, Hpy188Ⅰ and Taq Ⅰ, respectively.Conclusions The three novel mutations in SLC25A13 gene of Chinese NICCD patients were first identified, suggesting that SLC25A13 mutation distributed in Chinese population is somewhat different from that in Japanese. Moreover, the PCR-RFLP diagnostic procedures established in this research provide valuable tools not only for the genetic diagnosis of NICCD but also for further molecular epidemiologic investigations in Chinese population.Acknowledgement We are grateful to all research subjects and their family

  1. Neonatal Venous Thromboembolism

    Directory of Open Access Journals (Sweden)

    Kristina M. Haley

    2017-06-01

    Full Text Available Neonates are the pediatric population at highest risk for development of venous thromboembolism (VTE, and the incidence of VTE in the neonatal population is increasing. This is especially true in the critically ill population. Several large studies indicate that the incidence of neonatal VTE is up almost threefold in the last two decades. Central lines, fluid fluctuations, sepsis, liver dysfunction, and inflammation contribute to the risk profile for VTE development in ill neonates. In addition, the neonatal hemostatic system is different from that of older children and adults. Platelet function, pro- and anticoagulant proteins concentrations, and fibrinolytic pathway protein concentrations are developmentally regulated and generate a hemostatic homeostasis that is unique to the neonatal time period. The clinical picture of a critically ill neonate combined with the physiologically distinct neonatal hemostatic system easily fulfills the criteria for Virchow’s triad with venous stasis, hypercoagulability, and endothelial injury and puts the neonatal patient at risk for VTE development. The presentation of a VTE in a neonate is similar to that of older children or adults and is dependent upon location of the VTE. Ultrasound is the most common diagnostic tool employed in identifying neonatal VTE, but relatively small vessels of the neonate as well as frequent low pulse pressure can make ultrasound less reliable. The diagnosis of a thrombophilic disorder in the neonatal population is unlikely to change management or outcome, and the role of thrombophilia testing in this population requires further study. Treatment of neonatal VTE is aimed at reducing VTE-associated morbidity and mortality. Recommendations for treating, though, cannot be extrapolated from guidelines for older children or adults. Neonates are at risk for bleeding complications, particularly younger neonates with more fragile intracranial vessels. Developmental alterations in the

  2. Oral hypoglycaemic agents in 118 diabetic pregnancies

    DEFF Research Database (Denmark)

    Hellmuth, E; Damm, P; Mølsted-Pedersen, L

    2000-01-01

    AIMS: To assess maternal and neonatal complications in pregnancies of diabetic women treated with oral hypoglycaemic agents during pregnancy. METHODS: A cohort study including all consecutively registered, orally treated pregnant diabetic patients set in a diabetic obstetrical service at a univer......AIMS: To assess maternal and neonatal complications in pregnancies of diabetic women treated with oral hypoglycaemic agents during pregnancy. METHODS: A cohort study including all consecutively registered, orally treated pregnant diabetic patients set in a diabetic obstetrical service...... compared to women treated with sulphonylurea or insulin (32 vs. 7 vs. 10%, P neonatal morbidity was observed between the orally treated and insulin-treated group; no cases of severe hypoglycaemia or jaundice were seen in the orally treated groups. However, in the group of women...

  3. 母亲妊娠期糖尿病新生儿围生期血糖干预临床分析%Clinical analysis of diabetic mother neonatal blood glucose intervention in the perinatal period

    Institute of Scientific and Technical Information of China (English)

    徐景华

    2016-01-01

    Objective To investigate the influences of different intervention in maternal gestational diabetes newborn(IDMs)on blood glucose and complications in the perinatal period.Methods 205 IDMs were divided into observation group and control group.The observation group was born within 1 hour after birth or use baby bottles or nasogastric(feeding)feeding 10% glucose 5mL/kg.1-2 hours,raw milk,2-3 hours after until the normal blood glucose 2 times in a row.The control group was given priority to with breastfeeding,feeding difficulty with artificial feeding.Born after 1h,2h,3h,6h,12h,24h,48h,blood sugar,high statistical neonatal hypoglycemia,neonatal bilirubin levels,neonatal diseases were monitored.Results There was no significant difference in incidence of hypoglycemia between the two groups (P >0 .0 5 ).Born after2 h and 3 h ,the glucose levels ofthe control group were (3 .0 1 ± 0.45)mmol/L,(3.02 ±0.51 )mmol/L,respectively,those in the observation group were (3.14 ±0.72)mmol/L, (3.18 ±0.69)mmol/L,there were significant differences between the two groups(t =3.901,4.236,all P 0.05 ).The incidence rate of hyperbilirubinemia in the observation group was 21.0%,which was significantly lower than the control group 8.6%,there was significant difference between the two groups(χ2 =5.216,P <0.05 ).Conclusion IDMs different intervention methods in the perinatal period can decrease the incidence of low blood sugar 2h,3h after birth,reduce the incidence of high neonatal bilirubin,and have no effect on other diseases of newborn babies.%目的:探讨母亲妊娠期糖尿病新生儿(IDMs)围生期不同干预方法对新生儿血糖及并发症的影响。方法选择 IDMs 205例,采用数字表法随机分为观察组105例和对照组100例。观察组于出生或生后1 h 内即用奶瓶或鼻饲(口饲)喂10%葡萄糖溶液5 mL/kg。间隔1~2 h 1次,出生后2~3 h 开奶,直至连续2次血糖检测正常。对照组以母乳喂养为主,喂养困难

  4. 574-586 Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting

    NARCIS (Netherlands)

    S. Ferrè (Silvia); J.H.F. de Baaij (Jeroen H.); P. Ferreira (Patrick); R. Germann (Roger); J.B.C. de Klerk (Johannes); A.P.M. Lavrijsen (Adriana); F. van Zeeland (Femke); H. Venselaar (Hanka); L.A.J. Kluijtmans (Leo A.); J.G. Hoenderop (Joost); R.J.M. Bindels (René)

    2014-01-01

    textabstractMutations in PCBD1 are causative for transient neonatal hyperphenylalaninemia and primapterinuria (HPABH4D). Until now, HPABH4D has been regarded as a transient and benign neonatal syndrome without complications in adulthood. In our study of three adult patients with homozygous mutations

  5. Pax6基因突变与胰腺发育和糖尿病发生关系的研究进展%Research progress of Pax6 gene mutation and development of pancreas and diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    陆玉凤; 刘丽梅

    2011-01-01

    Paired box 6(Pax6) is one of the members of Pax polygene transcription factor family, and plays an important role in the development of pancreas, α cell differentiation, transcription and activation of glucagon gene, β cell function and expression of insulin. Pax6 is the major gene in regulating the development of β cells, and its mutation contributes to the pathogenesis of impaired glucose tolerance and early-onset diabetes mellitus. The research progress of associations of Pax6 mutation with development of pancreas and diabetes mellitus is reviewed in this paper.%配对盒因子6(Pax6)基因是Pax多基因转录因子家族成员之一,是与胰腺发育、α细胞分化、高血糖素基因的转录和激活、β细胞功能以及胰岛素表达密切相关的关键转录因子,在众多调节β细胞发育的基因中发挥中心作用,其突变/变异已成为糖耐量异常和早发糖尿病的致病原因或易感位点.该文就Pax6基因突变与胰腺发育及糖尿病发病关系的研究进展进行综述.

  6. 以心力衰竭为突出表现的线粒体基因突变糖尿病临诊应对%Approach to the patient with mitochondrial gene mutation diabetes mellitus mainly manifested as heart failure: diagnosis and treatment

    Institute of Scientific and Technical Information of China (English)

    苏杭; 周健; 潘静薇; 马晓静; 章紫晨; 张蓉; 胡承; 刘芳; 包玉倩

    2015-01-01

    Mitochondrial gene mutation diabetes,a special type of diabetes genetic mutation in beta cell,mainly caused by mutations in mitochondrial DNA.Clinical syndromes of mitochondrial gene mutation diabetes is frequent multisystemic disease involved,predominantly presents with central nervous system involvement,myopathy,cardiomyopathy,retinitis pigmentosa,and nerve deafness.Herein,we report in detail a case with mitochondrial gene mutation diabetes mellitus mainly manifested as heart failure,in order to call attention to the diagnosis and treatment of mitochondrial cardiomyopathy.%线粒体基因突变糖尿病是由线粒体DNA突变所致单基因病变,为β细胞功能遗传突变的一种特殊类型糖尿病.临床上常伴中枢神经系统表现、骨骼肌表现、心肌病、视网膜色素变性、神经性耳聋等.本文详细介绍l例以心力衰竭为突出表现的线粒体基因突变糖尿病的诊治经过,以使临床医师重视线粒体心肌病的诊治.

  7. Does Time of Delivery Influence the Risk of Neonatal Morbidity?

    Science.gov (United States)

    Brookfield, Kathleen F; O'Malley, Katharine; El-Sayed, Yasser Y; Blumenfeld, Yair J; Butwick, Alexander J

    2016-04-01

    To examine whether time of delivery influences the risk of neonatal morbidity among women with singleton pregnancies. Secondary analysis of data from the Maternal Fetal Medicine Units Network Factor V Leiden Mutation study. We categorized time of delivery as day (07:00-16:59), evening (17:00-23:59), and overnight (midnight-06:59). Severe neonatal morbidity was defined by at least one of the following: respiratory distress syndrome, transient tachypnea of the newborn, sepsis, seizures, neonatal intensive care admission, or a 5-minute APGAR ≤3. We calculated frequencies of severe neonatal morbidity by time of delivery. Multivariate analysis was performed to determine whether time of delivery was independently associated with severe neonatal morbidity. Among 4,087 women, 1,917 (46.9%) delivered during the day, 1,140 (27.9%) delivered in the evening, and 1,030 (25.2%) delivered overnight. We observed no significant differences in the rates of neonatal morbidity between delivery time periods (day: 12.3%; evening: 12.8%; overnight: 12.6%; p = 0.9). No significant association was observed between time of delivery and neonatal morbidity after adjustment for maternal, obstetric, and peripartum factors. Our findings suggest that time of delivery is not associated with severe neonatal morbidity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Rosiglitazone treatment of patients with extreme insulin resistance and diabetes mellitus due to insulin receptor mutations has no effects on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Vestergaard, H; Lund, S; Pedersen, O;

    2001-01-01

    Rosiglitazone, a thiazolidinedione (TZD), increases insulin sensitivity by reducing levels of plasma NEFA, triglycerides (TG), glucose and serum insulin. Rosiglitazone treatment decreases insulin resistance in type 2 diabetic patients, but no data exist concerning rosiglitazone treatment of patie...

  9. Neonatal septic arthritis.

    Science.gov (United States)

    Halder, D; Seng, Q B; Malik, A S; Choo, K E

    1996-09-01

    Neonatal septic arthritis has always been considered as separate from its counterpart in older children. The condition is uncommon but serious. Affected neonates usually survive, but with permanent skeletal deformities. Ten cases of neonatal septic arthritis were diagnosed between January 1989 and December 1993 in the neonatal intensive care units of two referral hospitals in the state of Kelantan, Malaysia. All except one neonate was born prematurely. The mean age of presentation was 15.6 days. Joint swelling (10/10), increased warmth (7/10) and erythema of the overlying skin (7/10) were the common presenting signs. Vague constitutional symptoms preceded the definitive signs of septic arthritis in all cases. The total white cell counts were raised with shift to the left. The knee (60%) was not commonly affected, followed by the hip (13%) and ankle (13%). Three neonates had multiple joint involvement. Coexistence of arthritis with osteomyelitis was observed in seven neonates. The commonest organism isolated was methicillin resistant Staphylococcus aureus (9/10). Needle aspiration was performed in nine neonates and one had incision with drainage. Follow up data was available for five neonates and two of these had skeletal morbidity. Early diagnosis by frequent examination of the joints, prompt treatment and control of nosocomial infection are important for management.

  10. Enterotoxemia in neonatal calves.

    Science.gov (United States)

    Fleming, S

    1985-11-01

    The incidence, bacterial characteristics, disease syndromes, diagnosis, treatment, and prevention of enterotoxemia of neonatal calves caused by Clostridium perfringens (Types A, B, C, D, and E) are reviewed.

  11. Risk of hearing loss in small for gestational age neonates

    Directory of Open Access Journals (Sweden)

    Melani Rakhmi Mantu

    2011-02-01

    Full Text Available Background Small for gestational age (SGA neonates often have intrauterine growth restriction due to placental insufficiency and chronic hypoxia. These conditions may cause developmental impairment, psychosocial disabilities, or metabolic dysfunction in later life. Previous studies have shown greater incidence of speech and language disabilities, learning impairment, and neuromotor dysfunction in term SGA infants compared to term appropriate for gestational age (AGA infants. Objective To compare hearing loss in SGA and AGA neonates using otoocoustic emission (OAE tests and to study correlations between maternal risk factors and hearing loss in SGA neonates. Methods A cross-sectional study was performed in St. Borromeus Hospital, Limijati Hospital, and Melinda Hospital in Bandung from February to May 2010. Study subjects consisted of full-term neonates born in these three hospitals. A retrospective medical record review was performed for this study. Statistical analysis was done by multivariable logistic-regression. Results There was a total of 4279 subjects in our study, including 100 SGA neonates and 4179 AGA neonates. We observed a greater percentage of OAE 'refer' (indicating abnormal OAE results in the SGA group compared to the AGA group (P<0.001, Z=13.247. For suhjects with OAE 'refer' results, we also analyzed the correlation to the following maternal risk factors: smoking, hypertension, diabetes mellitus and asthma. We also found significant differences between  those with and without each of the four maternal risk factors studied (P< 0.001. By using multivariant analysis to compare SGA and AGA neonates, we found the odds ratio (OR to he 4.34 (95% CI 2.52 to 7.49, P=0.001, meaning the SGA group had a 4.34 times higher risk of hearing loss than the AGA group. Conclusion SGA neonates had a higher risk of hearing loss than AGA neonates. In addition, maternal smoking, hypertension, diabetes mellitus and asthma significantly correlated to

  12. Avaliação da incidência das mutações G1691A no gene do fator V (fator V Leiden e G20210A no gene da protrombina em pacientes com diabetes mellitus tipo 2 Incidence of G1691A factor V gene (factor V Leiden and G20210A prothrombin gene mutations in type 2 diabetes patients

    Directory of Open Access Journals (Sweden)

    Anna L. Soares

    2005-09-01

    Full Text Available Em virtude da alta prevalência de Diabetes mellitus tipo 2 (DM2 na população mundial e da alta taxa de mortalidade decorrente de eventos trombóticos, é de extrema importância o conhecimento das alterações no sistema hemostático em pacientes portadores deste distúrbio. A mutação no gene do fator V (G1691A - fator V Leiden em heterozigose ou homozigose confere aos portadores o fenótipo de resistência à proteína C ativada, situação que aumenta em sete vezes o risco de desenvolver uma trombose. A mutação G20210A no gene da protrombina resulta no quadro de hiperprotrombinemia, aumentando o risco de trombose em três vezes. A pesquisa dessas mutações de interesse em trombofilia é de grande relevância considerando que a presença das mesmas pode exacerbar o estado de hipercoagulabilidade acelerando as complicações no diabetes. O presente estudo teve como objetivo avaliar a incidência dessas mutações em indivíduos hígidos (Controle, n=16, pacientes com DM2 (n=7, com hipertensão (HAS, n=12 e com DM2+HAS (n=18, através da técnica de PCR-RFLP. As freqüências encontradas nos grupos estudados foram baixas e similares àquelas observadas na população brasileira em geral. Não foi possível estabelecer correlação entre a presença da mutação e características específicas de cada grupo. Dessa forma, ainda não está claro se há ou não uma maior prevalência dessas mutações em indivíduos diabéticos e se a presença das mesmas contribui para o aumento do risco de desenvolver trombose nesses indivíduos, sendo necessário estudos mais amplos para a elucidação da questão.Because of the high prevalence of type 2 diabetes mellitus (DM2 worldwide and the high mortality rate due to thrombotic events, it is extremely important to know about changes in the hemostatic system of such patients. Factor V mutation (G1691A - factor V Leiden in either heterozygosis or homozygosis confers the activated protein C resistant

  13. A novel stop codon mutation in exon 1 (558C>A) of the UGT1A1 gene in a Thai neonate with Crigler-Najjar syndrome type I.

    Science.gov (United States)

    Wanlapakorn, N; Nilyanimit, P; Vorawandthanachai, T; Deesudjit, T; Dumrongpisutikul, N; Poovorawan, Y

    2015-01-23

    Human uridine 5'-diphosphate-glucuronosyltransferases play a critical role in detoxification by conjugating bilirubin with glucoronic acid. Impaired or reduced enzymatic activity causes a spectrum of clinical disorders such as Crigler-Najjar syndrome type I (CN1), Crigler-Najjar syndrome type II, and Gilbert's syndrome. CN1 is a severe form of unconjugated hyperbilirubinemia caused by homozygous or compound heterozygous mutations in the gene for uridine 5'-diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1), resulting in complete loss of enzyme function. Here, we report a novel homozygous mutation of UGT1A1 in a female Thai infant who was diagnosed with CN1, and her parents were found to be heterozygous carriers. The patient was homozygous for the c.558C>A mutation, which resulted in a premature stop codon in exon 1. Her asymptomatic parents were carriers of the nonsense c.558C>A mutation. Our result suggests an important role for homozygous c.558C>A mutations in the UGT1A1 gene in the development of severe unconjugated hyperbilirubinemia.

  14. Adverse pregnancy and neonatal outcomes in polycystic ovary syndrome women

    Directory of Open Access Journals (Sweden)

    Roshan Nikbakht

    2016-02-01

    Full Text Available Background: Polycystic ovary syndrome (PCOS is the most common endocrine disorders in reproductive age women. These women confer with complications of pregnancy such as gestational diabetes, pregnancy-induced hypertension, preeclampsia and neonatal complications such as small for gestational diabetes (SGA are more prevalence in women with PCOS. The aim of this study was to evaluate the incidence of complications associated with PCOS in pregnant women. Methods: This was an observational and prospective study which recruited 205 pregnant women with PCOS from Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences (AJUMS between 2013 and 2014. Inclusion criteria were women with PCOS and gestational age over 20 weeks. The demographic and clinical variables including mother's age, body mass index (BMI and conditions of pregnancy including pregnancy-induced hypertension, preeclampsia, gestational diabetes and overt diabetes and neonatal complications such as preterm labor (PTL, SGA and intrauterine fetal death (IUFD were recorded. Results: The prevalence of hypertension disorders, preeclampsia, gestational diabetes and overt diabetes were observed in 44 (21.5%, 18 (8.8%, 29 (14% and 22 (11% patients, respectively. The history of familial diabetes was shown in 28 patients (13.6%. In addition, the history of pregnancy induced hypertension was reported in 25 patients (12.1%. Only 6 patients (2.9% had history of gestational diabetes. Among neonatal complications due to PCOS, SGA with 15.3% and then PTL with 12.6% had highest prevalence. IUFD was shown only in 2 patients. Conclusion: Pregnant women with PCOS are at the higher risk for pregnancy and neonatal complications. Specifically, these women should be evaluated for pregnancy induced hypertension during pregnancy than others.

  15. Gestational Diabetes Mellitus (GDM) on Maternal and Neonatal Outcomes of Pregnant Women with Different Blood Glucose Abnormalities%妊娠期糖尿病(GDM)孕妇不同血糖指标异常的母婴结局研究

    Institute of Scientific and Technical Information of China (English)

    冯艳红

    2016-01-01

    Objective To study the effect of gestational diabetes mellitus (GDM) pregnant women with different glycemic in-dex of abnormal pregnancy outcome. Methods Admitted to our hospital with 300 cases of pregnancy with gestational dia-betes mellitus pregnant women and 150 cases of normal pregnant women as the observation object, the admitted time for June 5, 2012 to 2015, the normal pregnant women as control group, the 300 cases of pregnancy with gestational diabetes, according to the degree of blood glucose control points for normal glycemic index group (158 cases) and abnormal blood glu-cose index group (142 cases), three groups of clinical data were retrospectively analyzed to observe the differences between the three groups of pregnant women, maternal and neonatal outcomes. Results Control group and blood sugar index normal group of pregnant women pregnancy differences between outcome was not significant (P > 0.05); control group and blood sugar index group of abnormal pregnant women, maternal and neonatal outcomes between the difference is significant (P0.05);对照组与血糖指标异常组孕妇母婴结局之间的差异有统计学意义(P<0.05);且血糖指标异常组与血糖指标正常组之间对比的母婴结局,差异具有统计学意义(P<0.05)。结论妊娠期糖尿病孕妇不同血糖指标对母婴结局的影响较大,临床中应注意控制孕妇的血糖水平,达到改善母婴结局的效果。

  16. HIGH MATERNAL HbA1c IS ASSOCIATED WITH NEONATAL HYPOCALCEMIA

    Directory of Open Access Journals (Sweden)

    Abdul Tawab

    2014-10-01

    Full Text Available INTRODUCTION: Hypocalcemia occurs within the first 72 hours of birth in up to 50% of IDMs. The objective of the study was to compare the incidence of hypocalcemia in Infants of Pre-Gestational Diabetic & Gestational Diabetic mothers and to find the association of hypocalcemia and maternal diabetic control. MATERIAL AND METHODS: A tertiary care teaching hospital based prospective study over a period of 2 years. 40 Cases were included in the study 20 breast fed full term infants of Gestational diabetic mothers and 20 breastfed full term infants of Pre-Gestational diabetic mothers were enrolled in the study. Serum calcium of neonates in both groups was sent at 48 hours of life. Mean maternal HbA1c level was used to access maternal diabetic control. OBSERVATION AND RESULTS: Neonates of GDM showed statistically significant change in the serum calcium levels (Mean calcium level 9.055 mg/dl and maternal HBA1c levels (mean HbA1c level 5.85% an compared to neonates of PGDM (Mean calcium level 8.015 mg/dl, mean HbA1c level 6.75% (p=0.0001. 7 out of 20 neonates (35 % of Pre Gestational Diabetic mothers had hypocalcemia at 48 hour postnatal age and 3 out of 20 neonates (15% of Gestational Diabetic mothers had hypocalcemia at 48 hour postnatal age. Incidence of hypocalcemia is more when diabetes is poorly controlled [HbA1C>6%] in both groups and it was statistically significant. CONCLUSION: Infants born to Pre-Gestational diabetic mothers are at a higher risk of developing hypocalcemia than infants of gestational diabetic mothers. Incidence of hypocalcemia can be predicted with diabetic control [maternal HbA1c levels]. Studies with larger sample size will give more definitive results on this issue.

  17. Complications in neonatal surgery.

    Science.gov (United States)

    Escobar, Mauricio A; Caty, Michael G

    2016-12-01

    Neonatal surgery is recognized as an independent discipline in general surgery, requiring the expertise of pediatric surgeons to optimize outcomes in infants with surgical conditions. Survival following neonatal surgery has improved dramatically in the past 60 years. Improvements in pediatric surgical outcomes are in part attributable to improved understanding of neonatal physiology, specialized pediatric anesthesia, neonatal critical care including sophisticated cardiopulmonary support, utilization of parenteral nutrition and adjustments in fluid management, refinement of surgical technique, and advances in surgical technology including minimally invasive options. Nevertheless, short and long-term complications following neonatal surgery continue to have profound and sometimes lasting effects on individual patients, families, and society. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Genetic causes and gene–nutrient interactions in mammalian zinc deficiencies: acrodermatitis enteropathica and transient neonatal zinc deficiency as examples.

    Science.gov (United States)

    Kasana, Shakhenabat; Din, Jamila; Maret, Wolfgang

    2015-01-01

    Discovering genetic causes of zinc deficiency has been a remarkable scientific journey. It started with the description of a rare skin disease, its treatment with various agents, the successful therapy with zinc, and the identification of mutations in a zinc transporter causing the disease. The journey continues with defining the molecular and cellular pathways that lead to the symptoms caused by zinc deficiency. Remarkably, at least two zinc transporters from separate protein families are now known to be involved in the genetics of zinc deficiency. One is ZIP4, which is involved in intestinal zinc uptake. Its mutations can cause acrodermatitis enteropathica (AE) with autosomal recessive inheritance. The other one is ZnT2, the transporter responsible for supplying human milk with zinc. Mutations in this transporter cause transient neonatal zinc deficiency (TNZD) with symptoms similar to AE but with autosomal dominant inheritance. The two diseases can be distinguished in affected infants. AE is fatal if zinc is not supplied to the infant after weaning, whereas TNZD is a genetic defect of the mother limiting the supply of zinc in the milk, and therefore the infant usually will obtain enough zinc once weaned. Although these diseases are relatively rare, the full functional consequences of the numerous mutations in ZIP4 and ZnT2 and their interactions with dietary zinc are not known. In particular, it remains unexplored whether some mutations cause milder disease phenotypes or increase the risk for other diseases if dietary zinc requirements are not met or exceeded. Thus, it is not known whether widespread zinc deficiency in human populations is based primarily on a nutritional deficiency or determined by genetic factors as well. This consideration becomes even more significant with regard to mutations in the other 22 human zinc transporters, where associations with a range of diseases, including diabetes, heart disease, and mental illnesses have been observed

  19. Correlation of prepregnancy weight and lipid levels of late pregnancy in gestational diabetes melli-tus with neonatal birth weight%妊娠期糖尿病孕妇孕前体质量和孕晚期血脂水平与新生儿出生体质量的关系

    Institute of Scientific and Technical Information of China (English)

    丁俊蓉; 周益伟; 徐静; 胡欣; 陈艳

    2014-01-01

    目的:研究妊娠期糖尿病孕妇孕前体质量和孕晚期血脂水平与新生儿出生体质量的关系。方法选择正常糖耐量孕妇(对照组)和妊娠期糖尿病孕妇(妊娠期糖尿病组)各52例,采用日立7080型全自动生化分析仪测定血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和脂蛋白(a)[LP(a)],同时记录两组孕妇的年龄、孕周、妊娠前体质量与新生儿出生体质量等。结果妊娠期糖尿病组孕前体质量、TG、LDL-C 均显著高于对照组,差异有统计学意义(P <0.05)。孕前体质量、TG 与新生儿出生体质量呈正相关(P <0.05),LP(a)与新生儿出生体质量呈负相关(P <0.05)。结论妊娠期糖尿病孕妇存在以 TG、LDL-C 升高为特点的高脂血症,与正常糖耐量孕妇相比,伴发了更为严重的血脂代谢异常,并明显影响着新生儿的出生体质量,因此对妊娠期糖尿病孕妇进行孕前体质量的控制、孕晚期血脂水平的监测和必要的饮食指导具有重要的临床意义。%Objective To investigate the relationship of prepregnancy weight and lipid levels of late pregnancy in gestational diabetes mellitus(GDM)with neonatal birth weight. Methods Fifty-two normal glucose tolerance(NGT)pregnant women(control group)and 52 pregnant women with gestational diabetes mellitus( GDM group)were chose. Hitachi 7080 automatic biochemical analyzer was used to measure the serum levels of total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol(LDL-C)and lipoprotein(a)[LP(a)]. At the same time, maternal age,gestational age,body weight before pregnancy and fetal birth weight were recorded in the two groups. Results Prepregnancy weight and the levels of TG and LDL-C were significantly higher in GDM group than those in control group(P <0. 01

  20. Primary trabeculodysgenesis in association with neonatal Marfan syndrome

    NARCIS (Netherlands)

    Whitelaw, CM; Anwar, S; Ades, LC; Gole, GA; Elder, JE; Savarirayan, R

    2004-01-01

    We present the clinical and ophthalmological findings in two infants with neonatal Marfan syndrome (nMFS) and primary trabeculodysgenesis (PT). Fibrillin 1 (FBN1) mutations were confirmed in both cases. Numerous eye anomalies have been recognized in infants with nMFS, but PT has not been reported pr

  1. Expression of three different mutations in the arginine vasopressin gene suggests genotype-phenotype correlation in familial neurohypophyseal diabetes insipidus kindreds

    DEFF Research Database (Denmark)

    Siggaard, Charlotte; Christensen, Jane Hvarregaard; Corydon, Thomas Juhl

    2005-01-01

    reduction of the amount of immunoreactive AVP in the cell culture medium and severe impairment of the intracellular trafficking and processing of the AVP prohormone, supporting the disease causing nature of all three mutations. However, the A19T mutation was associated with some capacity for processing...... and trafficking consistent with the clinical observations. Immunoflourescence studies provided evidence of reticular accumulation of protein within the ER in the A19T and C110X mutants but a unique accumulation of much larger aggregates in the L81P, which were localized both within and immediately outside the ER...

  2. Diabetes and perinatal mortality in twin pregnancies.

    Directory of Open Access Journals (Sweden)

    Zhong-Cheng Luo

    Full Text Available BACKGROUND: Diabetes in pregnancy has been associated with a paradoxically reduced risk of neonatal death in twin pregnancies. Risk "shift" may be a concern in that the reduction in neonatal deaths may be due to an increase in fetal deaths (stillbirths. This study aimed to clarify the impact of diabetes on the risk of perinatal death (neonatal death plus stillbirth in twin pregnancies. METHODS: This was a retrospective cohort study of twin births using the largest available dataset on twin births (the U.S. matched multiple birth data 1995-2000; 19,676 neonates from diabetic pregnancies, 541,481 from non-diabetic pregnancies. Cox proportional hazard models were applied to estimate the adjusted hazard ratios (aHR of perinatal death accounting for twin cluster-level dependence. RESULTS: Comparing diabetic versus non-diabetic twin pregnancies, overall perinatal mortality rate was counterintuitively lower [2.1% versus 3.3%, aHR 0.70 (95% confidence intervals 0.63-0.78]. Individually, both stillbirth and neonatal mortality rates were lower in diabetic pregnancies, but we identified significant differences by gestational age and birth weight. Diabetes was associated with a survival benefit in pregnancies completed before 32 weeks [aHR 0.55 (0.48-0.63] or with birth weight =2500 g [aHR 2.20 (1.55-3.13]. CONCLUSIONS: Diabetes in pregnancy appears to be "protective" against perinatal death in twin pregnancies ending in very preterm or very low birth weight births. Prospective studies are required to clarify whether these patterns of risk are real, or they are artifacts of unmeasured confounders. Additional data correlating these outcomes with the types of diabetes in pregnancy are also needed to distinguish the effects of pre-gestational vs. gestational diabetes.

  3. Maternal diabetes and the fetal heart

    OpenAIRE

    Hornberger, L K

    2006-01-01

    Maternal diabetes mellitus significantly affects the fetal heart and fetal–placental circulation in both structure and function. The influence of pre‐conceptional diabetes begins during embryonic development in the first trimester, with altered cardiac morphogenesis and placental development. It continues to have an influence on the fetal circulation through the second and third trimesters and into the perinatal and neonatal period

  4. [Congenital nephrogenic diabetes insipidus: about a case report].

    Science.gov (United States)

    Esselmani, Hicham; Yassine, Asmaa; Bouabdellah, Mounya; Benchekroun, Laila; Handor, Najat; Elalami, Sanae; Chabraoui, Layachi

    2013-01-01

    Congenital nephrogenic diabetes insipidus is a rare, hereditary in nature, characterized by an inability of the kidney to concentrate urine, secondary to the manifold resistance to the action of vasopressin. X-linked forms of transmission (90%) are expressed in boys, from the neonatal period in general, by polyuria and polydipsia. Symptomatology in transmissive girls is variable but can sometimes be quite marked. These forms are secondary to mutations in the gene encoding the vasopressin V2 receptor, located at position Xq28, responsible for a loss of function of this receptor. Some of these mutations may cause a partial phenotype, less severe. Forms of autosomal, recessive or dominant are more rare (10%). Treatment is symptomatic, sometimes difficult in infants. It aims to avoid episodes of dehydration. It is based on a conventional diet hypo-osmotic and administration of hydrochlorothiazide and indomethacin. We report here the case of a child with congenital nephrogenic diabetes insipidus hospitalized at Children's Hospital of Rabat and throughout this case we review the pathophysiology and clinical and biological characteristics of the disease and including importance of contribution of clinical biochemistry laboratory in the diagnosis and monitoring of this disease.

  5. Vitamin D and neonatal immune function.

    LENUS (Irish Health Repository)

    Clancy, N

    2013-05-01

    Vitamin D deficiency is widespread in the neonatal and paediatric population of northern latitudes, particularly in children of African, Middle Eastern and Asian ethnicity. This is associated with diminished immune function and increases the risk of Th1 autoimmune diseases like type 1 diabetes. Epidermiological studies have also shown a link between vitamin D deficiency in children and a more severe course of illness with lower respiratory tract infection or Respiratory Syncitial Virus (RSV) bronchiolitis. The mechanism by which vitamin D enhances immunity is complex. It acts through the innate immune system by inducing antimicrobial peptides in epithelial cells, neutrophils and macrophages. The role of Vitamin D in neonatal and paediatric immunomodulation requires further study.

  6. The neonatal chest

    Energy Technology Data Exchange (ETDEWEB)

    Lobo, Luisa [Servico de Imagiologia Geral do Hospital de Santa Maria, Av. Prof. Egas Moniz, 1649-035 Lisbon (Portugal)]. E-mail: mluisalobo@gmail.com

    2006-11-15

    Lung diseases represent one of the most life threatening conditions in the newborn. Important progresses in modern perinatal care has resulted in a significantly improved survival and decreased morbidity, in both term and preterm infants. Most of these improvements are directly related to the better management of neonatal lung conditions, and infants of very low gestational ages are now surviving. This article reviews the common spectrum of diseases of the neonatal lung, including medical and surgical conditions, with emphasis to the radiological contribution in the evaluation and management of these infants. Imaging evaluation of the neonatal chest, including the assessment of catheters, lines and tubes are presented.

  7. Transient neonatal cyanosis associated with a new Hb F variant: Hb F viseu.

    Science.gov (United States)

    Bento, Celeste; Magalhães Maia, Tabita; Carvalhais, Ines; Moita, Filipa; Abreu, Gabriela; Relvas, Luis; Pereira, Alexandra; Farela Neves, José; Ribeiro, Maria L

    2013-03-01

    Neonatal cyanosis in healthy newborns can be associated either with methemoglobin due to cytochrome b5 reductase deficiency or to M-hemoglobin, a group of hemoglobin variants resulting from mutations in the globin chain genes. We report the clinical case of a neonate with cyanosis and normal cardiac and respiratory function. At birth the hematological parameters were normal; however, the methemoglobinemia was 16%. Spontaneously, the cyanosis gradually decreased and by the fifth month of age the methemoglobin level was normal. A heterozygous Gγ-globin gene (HBG2) missense mutation 87 C-A (Leu28Met) was identified. His father, with a history of transfusion in the neonatal period, is heterozygous for the same mutation. This hemoglobin variant, not previously described, was called Hb F Viseu and is the sixth Gγ-chain variant reported in association with neonatal cyanosis.

  8. Monitoring neonates for ototoxicity.

    Science.gov (United States)

    Garinis, Angela C; Kemph, Alison; Tharpe, Anne Marie; Weitkamp, Joern-Hendrik; McEvoy, Cynthia; Steyger, Peter S

    2017-06-22

    Neonates admitted to the neonatal intensive care unit (NICU) are at greater risk of permanent hearing loss compared to infants in well mother and baby units. Several factors have been associated with this increased prevalence of hearing loss, including congenital infections (e.g. cytomegalovirus or syphilis), ototoxic drugs (such as aminoglycoside or glycopeptide antibiotics), low birth weight, hypoxia and length of stay. The aetiology of this increased prevalence of hearing loss remains poorly understood. Here we review current practice and discuss the feasibility of designing improved ototoxicity screening and monitoring protocols to better identify acquired, drug-induced hearing loss in NICU neonates. A review of published literature. We conclude that current audiological screening or monitoring protocols for neonates are not designed to adequately detect early onset of ototoxicity. This paper offers a detailed review of evidence-based research, and offers recommendations for developing and implementing an ototoxicity monitoring protocol for young infants, before and after discharge from the hospital.

  9. Neonatal pain management

    Directory of Open Access Journals (Sweden)

    Tarun Bhalla

    2014-01-01

    Full Text Available The past 2-3 decades have seen dramatic changes in the approach to pain management in the neonate. These practices started with refuting previously held misconceptions regarding nociception in preterm infants. Although neonates were initially thought to have limited response to painful stimuli, it was demonstrated that the developmental immaturity of the central nervous system makes the neonate more likely to feel pain. It was further demonstrated that untreated pain can have long-lasting physiologic and neurodevelopmental consequences. These concerns have resulted in a significant emphasis on improving and optimizing the techniques of analgesia for neonates and infants. The following article will review techniques for pain assessment, prevention, and treatment in this population with a specific focus on acute pain related to medical and surgical conditions.

  10. Sonomammography in Neonatal Mastauxe

    Directory of Open Access Journals (Sweden)

    Sushil Ghanshyam Kachewar

    2015-03-01

    Full Text Available Prominence or even enlargement of one or both breasts is known in neonates. It is believed to be a physiological response to falling levels of maternal estrogen towards last trimester of pregnancy. This input stimulates prolactin release from the newborn's pituitary leading to transient neonatal breast enlargement. This phenomenon is independent of the gender of the neonate. It presents in the first few weeks of life and resolves subsequently. Often fluid discharge is noted from the prominent or swollen breast that resolves without treatment in subsequent weeks. Manual breast manipulation for discharge removal may lead to undesirable effects like local irritation, enhanced enlargement, prolonged tissue hypertropy or even mastitis. A case of such 7-days female neonate is presented here backed with imaging evaluation for confirmation of diagnosis. Typical sonomammographic findings are described. [Cukurova Med J 2015; 40(Suppl 1: 22-24

  11. Maternal and neonatal tetanus

    Science.gov (United States)

    Thwaites, C Louise; Beeching, Nicholas J; Newton, Charles R

    2017-01-01

    Maternal and neonatal tetanus is still a substantial but preventable cause of mortality in many developing countries. Case fatality from these diseases remains high and treatment is limited by scarcity of resources and effective drug treatments. The Maternal and Neonatal Tetanus Elimination Initiative, launched by WHO and its partners, has made substantial progress in eliminating maternal and neonatal tetanus. Sustained emphasis on improvement of vaccination coverage, birth hygiene, and surveillance, with specific approaches in high-risk areas, has meant that the incidence of the disease continues to fall. Despite this progress, an estimated 58 000 neonates and an unknown number of mothers die every year from tetanus. As of June, 2014, 24 countries are still to eliminate the disease. Maintenance of elimination needs ongoing vaccination programmes and improved public health infrastructure. PMID:25149223

  12. Correction of Neonatal Hypovolemia

    Directory of Open Access Journals (Sweden)

    V. V. Moskalev

    2007-01-01

    Full Text Available Objective: to evaluate the efficiency of hydroxyethyl starch solution (6% refortane, Berlin-Chemie versus fresh frozen plasma used to correct neonatal hypovolemia.Materials and methods. In 12 neonatal infants with hypoco-agulation, hypovolemia was corrected with fresh frozen plasma (10 ml/kg body weight. In 13 neonates, it was corrected with 6% refortane infusion in a dose of 10 ml/kg. Doppler echocardiography was used to study central hemodynamic parameters and Doppler study was employed to examine regional blood flow in the anterior cerebral and renal arteries.Results. Infusion of 6% refortane and fresh frozen plasma at a rate of 10 ml/hour during an hour was found to normalize the parameters of central hemodynamics and regional blood flow.Conclusion. Comparative analysis of the findings suggests that 6% refortane is the drug of choice in correcting neonatal hypovolemia. Fresh frozen plasma should be infused in hemostatic disorders. 

  13. Hiperbilirrubinemia neonatal agravada Aggravated neonatal hyperbilirubinemia

    Directory of Open Access Journals (Sweden)

    Ana Campo González

    2010-09-01

    Full Text Available INTRODUCCIÓN. La mayoría de las veces la ictericia en el recién nacido es un hecho fisiológico, causado por una hiperbilirrubinemia de predominio indirecto, secundario a inmadurez hepática e hiperproducción de bilirrubina. El objetivo de este estudio fue determinar el comportamiento de la hiperbilirrubinemia neonatal en el Hospital Docente Ginecoobstétrico de Guanabacoa en los años 2007 a 2009. MÉTODOS. Se realizó un estudio descriptivo y retrospectivo de 173 recién nacidos que ingresaron al Departamento de Neonatología con diagnóstico de hiperbilirrubinemia agravada. RESULTADOS. La incidencia de hiperbilirrubinemia neonatal agravada fue del 3,67 % y predominó en hermanos con antecedentes de ictericia (56,65 %. El tiempo de aparición fue de 48 a 72 h (76,87 % y entre los factores agravantes se hallaron el nacimiento pretérmino y el bajo peso al nacer. La mayoría de los pacientes fueron tratados con luminoterapia (90,17 %. CONCLUSIÓN. La hiperbilirrubinemia neonatal agravada constituye un problema de salud. Los factores agravantes son la prematuridad y el bajo peso al nacer. La luminoterapia es una medida terapéutica eficaz para su tratamiento.INTRODUCTION. Most of times jaundice in newborn is a physiological fact due to hyperbilirubinemia of indirect predominance, secondary to liver immaturity and to bilirubin hyperproduction. The aim of present of present study was to determine the behavior of neonatal hyperbilirubinemia in the Gynecology and Obstetrics Teaching Hospital of Guanabacoa municipality from 2007 to 2009. METHODS. A retrospective and descriptive study was conducted in 173 newborn patients admitted in the Neonatology Department diagnosed with severe hyperbilirubinemia. RESULTS. The incidence of severe neonatal hyperbilirubinemia was of 3,67% with predominance in brothers with a history of jaundice (56,65%. The time of appearance was of 48 to 72 hrs (76,87% and among the aggravating factors were the preterm birth and

  14. Gestational diabetes mellitus

    OpenAIRE

    2011-01-01

    Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy. It is associated with maternal and neonatal adverse outcomes. Maintaining adequate blood glucose levels in GDM reduces morbidity for both mother and baby. There is a lack of uniform strategies for screening and diagnosing GDM globally. This review covers the latest update in the diagnosis and management of GDM. The initial treatment of GDM consists of diet and exercise. If these measures fail to achieve ...

  15. Update on diabetes classification.

    Science.gov (United States)

    Thomas, Celeste C; Philipson, Louis H

    2015-01-01

    This article highlights the difficulties in creating a definitive classification of diabetes mellitus in the absence of a complete understanding of the pathogenesis of the major forms. This brief review shows the evolving nature of the classification of diabetes mellitus. No classification scheme is ideal, and all have some overlap and inconsistencies. The only diabetes in which it is possible to accurately diagnose by DNA sequencing, monogenic diabetes, remains undiagnosed in more than 90% of the individuals who have diabetes caused by one of the known gene mutations. The point of classification, or taxonomy, of disease, should be to give insight into both pathogenesis and treatment. It remains a source of frustration that all schemes of diabetes mellitus continue to fall short of this goal.

  16. Peripartum management of diabetes

    Directory of Open Access Journals (Sweden)

    Pramila Kalra

    2013-01-01

    Full Text Available The peripartum control of diabetes is very important for the well-being of the newborn as higher incidence of neonatal hypoglycemia is seen if maternal hyperglycemia happens during this period. Type of diabetes (type 1, type 2 or gestational diabetes also has an effect on the glucose concentration during intrapartum period. During the latent phase of labor, the metabolic demands are stable but during active labor there is increased metabolic demand and decreased insulin requirement. After delivery once the placenta is extracted, insulin resistance rapidly comes down and in patients with pre-gestational diabetes there will be a sudden drop in insulin requirement and the insulin may not be required in women with gestational diabetes, but they just need close monitoring. During breast-feeding blood glucose levels fall because of high metabolic demand and women need to take extra calories to maintain the levels and more vigilance especially in type 1 and type 2 diabetic mothers is required. The protocols used for the management of peripartum management of diabetes mostly rely on glucose and insulin infusion to maintain maternal blood sugars between 70 and 110 mg/dl. The data is mostly from retrospective studies and few randomized control trials done mainly in type 1 diabetes patients. The review summarizes guidelines, which are used for peripartum management of blood glucose.

  17. Neonatal renal vein thrombosis.

    Science.gov (United States)

    Brandão, Leonardo R; Simpson, Ewurabena A; Lau, Keith K

    2011-12-01

    Neonatal renal vein thrombosis (RVT) continues to pose significant challenges for pediatric hematologists and nephrologists. The precise mechanism for the onset and propagation of renal thrombosis within the neonatal population is unclear, but there is suggestion that acquired and/or inherited thrombophilia traits may increase the risk for renal thromboembolic disease during the newborn period. This review summarizes the most recent studies of neonatal RVT, examining its most common features, the prevalence of acquired and inherited prothrombotic risk factors among these patients, and evaluates their short and long term renal and thrombotic outcomes as they may relate to these risk factors. Although there is some consensus regarding the management of neonatal RVT, the most recent antithrombotic therapy guidelines for the management of childhood thrombosis do not provide a risk-based algorithm for the acute management of RVT among newborns with hereditary prothrombotic disorders. Whereas neonatal RVT is not a condition associated with a high mortality rate, it is associated with significant morbidity due to renal impairment. Recent evidence to evaluate the effects of heparin-based anticoagulation and thrombolytic therapy on the long term renal function of these patients has yielded conflicting results. Long term cohort studies and randomized trials may be helpful to clarify the impact of acute versus prolonged antithrombotic therapy for reducing the morbidity that is associated with neonatal RVT.

  18. GCK-MODY diabetes as a protein misfolding disease: the mutation R275C promotes protein misfolding, self-association and cellular degradation.

    Science.gov (United States)

    Negahdar, Maria; Aukrust, Ingvild; Molnes, Janne; Solheim, Marie H; Johansson, Bente B; Sagen, Jørn V; Dahl-Jørgensen, Knut; Kulkarni, Rohit N; Søvik, Oddmund; Flatmark, Torgeir; Njølstad, Pål R; Bjørkhaug, Lise

    2014-01-25

    GCK-MODY, dominantly inherited mild hyperglycemia, is associated with more than 600 mutations in the glucokinase gene. Different molecular mechanisms have been shown to explain GCK-MODY. Here, we report a Pakistani family harboring the glucokinase mutation c.823C>T (p.R275C). The recombinant and in cellulo expressed mutant pancreatic enzyme revealed slightly increased enzyme activity (kcat) and normal affinity for α-D-glucose, and resistance to limited proteolysis by trypsin comparable with wild-type. When stably expressed in HEK293 cells and MIN6 β-cells (at different levels), the mutant protein appeared misfolded and unstable with a propensity to form dimers and aggregates. Its degradation rate was increased, involving the lysosomal and proteasomal quality control systems. On mutation, a hydrogen bond between the R275 side-chain and the carbonyl oxygen of D267 is broken, destabilizing the F260-L271 loop structure and the protein. This promotes the formation of dimers/aggregates and suggests that an increased cellular degradation is the molecular mechanism by which R275C causes GCK-MODY.

  19. 妊娠期糖尿病患者血糖水平与新生儿出生体重关系分析%The Analysis of the Relationship for Gestational Diabetes Blood Sugar Levels in Patients with Neonatal Birth Weight

    Institute of Scientific and Technical Information of China (English)

    姜百灵; 张方芳

    2014-01-01

    Objective:To further investigate the relationship for gestational diabetes blood sugar levels in patients with neonatal birth weight. Method:124 cases of pregnant women admitted to our hospital from January 2009 to April 2012 were chosen as the research object.The clinical information of pregnant women was analyzed and studied retrospectively. Result:(1)In fasting glucose levels and neonatal birth weight,the gestational diabetes group was higher than the healthy control group,the difference was statistically significant(P<0.05).(2)In the incidence of huge children, the pregnancy diabetic group was higher than healthy control group,the difference was statistically significant(P<0.05).(3)Neonatal birth weight and maternal glucose levels of the gestational diabetes group and the healthy control group showed a positive relationship. Conclusion:Gestational diabetes blood sugar levels with birth weight shows a positive relationship,so monitoring blood sugar levels for pregnant women has important implications for the prevention of the occurrence of a huge child.%目的:进一步探讨妊娠期糖尿病患者血糖水平与新生儿出生体重之间的相关性。方法:选取本院2009年1月-2012年4月收治的124例孕妇为研究对象,针对孕妇的临床资料进行了回顾性分析和研究。结果:(1)在空腹血糖水平和新生儿出生体重两方面,妊娠糖尿病组均高于健康对照组,差异具有统计学意义(P<0.05);(2)在巨大儿发生率方面,妊娠糖尿病组高于健康对照组,差异具有统计学意义(P<0.05);(3)妊娠糖尿病组和健康对照组新生儿出生体重与孕妇血糖水平呈现出正相关的关系。结论:妊娠期糖尿病患者血糖水平与新生儿出生体重之间呈现出正相关的关系,因此针对孕妇血糖水平进行监测,对于预防巨大儿的发生具有重要的意义。

  20. Two novel RFX6 variants in siblings with Mitchell-Riley syndrome with later diabetes onset and heterotopic gastric mucosa.

    Science.gov (United States)

    Skopkova, Martina; Ciljakova, Miriam; Havlicekova, Zuzana; Vojtkova, Jarmila; Valentinova, Lucia; Danis, Daniel; Murgas, Dalibor; Szepeova, Renata; Stanik, Juraj; Banovcin, Peter; Klimes, Iwar; Gasperikova, Daniela

    2016-09-01

    Mitchell-Riley syndrome, an autosomal recessive disorder caused by mutations in the RFX6 gene, is defined as a combination of neonatal diabetes mellitus and serious congenital gastrointestinal defects. We describe Mitchell-Riley syndrome in two sisters with two novel compound heterozygous variants in the RFX6 gene: c.1154G > A, p.(Arg385Gln), and c.1316_1319delTCTA, p.(Ile439Thrfs*13). Both sisters present milder forms of the syndrome, likely due to possible residual activity of the p.Arg385Gln variant, which is localized in a dimerization domain of the RFX6 transcription factor. We propose that the prognosis is dependent on patient RFX6 genotype and possible residual activity of RFX6 transcription factor. Both sisters had atypical later onset of diabetes, at 2 years and 10 months and 2 years and 7 months, respectively. This supports the need of extending the definition of diabetes in Mitchell-Riley syndrome from neonatal to childhood onset and regular glyceamia check in patients with gastrointestinal tract malformations typical for Mitchell-Riley syndrome. The clinical course in both sisters improved significantly after surgical removal of parts of the small intestine with heterotopic gastric mucosa. We suggest that gastric mucosa heterotopy is an important actionable part of Mitchell-Riley syndrome and could have been responsible for the malabsorption, failure to thrive and severe anemia present in previously reported patients with Mitchell-Riley syndrome.

  1. A case of pancreatic agenesis and congenital heart defects with a novel GATA6 nonsense mutation: evidence of haploinsufficiency due to nonsense-mediated mRNA decay.

    Science.gov (United States)

    Suzuki, Shigeru; Nakao, Atsushi; Sarhat, Ashoor R; Furuya, Akiko; Matsuo, Kumihiro; Tanahashi, Yusuke; Kajino, Hiroki; Azuma, Hiroshi

    2014-02-01

    Recently, GATA6 heterozygous loss-of-function mutations were reported to cause pancreatic agenesis and congenital heart defects (PACHD [OMIM:600001]). However, the molecular mechanisms resulting from premature termination codons have not been examined in this disorder. The objective of this study was to perform a genetic analysis of a patient with PACHD. A female patient presented with ventricular septal defect, patent ductus arteriosus, and congenital diaphragmatic hernia at birth. Permanent neonatal diabetes mellitus and pancreatic exocrine deficiency due to pancreatic agenesis was diagnosed at 1 month of age. PCR-direct sequencing of GATA6 revealed that the patient is heterozygous for a novel de novo nonsense mutation of c.1477C>T, p. Arg493X in exon 5. RT-PCR direct sequencing of the RT-PCR products of total RNA from peripheral blood of the patient for the region encompassing exons 4-6 revealed only the wild-type allele. This finding provides the evidence for the occurrence of nonsense-mediated mRNA decay (NMD) in the p.Arg493X mutation. Quantitative RT-PCR analysis revealed that the expression of GATA6 transcript in the patient was less than half compared with normal control samples. This is the first evidence that GATA6 haploinsufficiency is caused by NMD in vivo, and we conclude that GATA6 haploinsufficiency causes not only PACHD but may affect other organs derived from the endoderm. Further screenings of GATA6 mutations in patients with various forms of diabetes and/or congenital heart disease with other visceral malformation may reveal the impact of GATA6 mutations on diabetes and congenital malformation.

  2. Pig model for diabetes

    DEFF Research Database (Denmark)

    2016-01-01

    The present invention relates to a transgenic pig comprising a mutated IAPP gene and displaying a phenotype associated with diabetes. The invention also relates to a transgenic blastocyst, embryo, fetus, donor cell and/or cell nucleusderived from said transgenic pig. The invention further relates...... to use of the transgenic pig as a model system for studying therapy, treatment and/or prevention of diabetes....

  3. 邯郸地区新生儿听力与药物性耳聋易感基因突变联合筛查研究%Neonatal hearing screening combined with drug-induced deafness susceptibility genes mutation screening in Handan area

    Institute of Scientific and Technical Information of China (English)

    陈丁莉; 李守霞; 要跟东; 冯海芹; 郭丽丽; 孙彩霞; 杨志明; 张晓芳

    2013-01-01

    Objectives To evaluate the feasibility and significance of universal neonatal hearing screening combined with mitochondria deafness genes screening using newborn cord blood. Methods One thousand newborns were enrolled in the study. Routine hearing screening was carried out and meanwhile the cord bloods were collected for mitochondria DNA screening. Mutations of A1555G and C1494T on mitochondria gene 12S rRNA were screened using Sanger sequencer. Results In hearing screening, 141 (14.1%) of the 1000 newborns were identified to be at risk, of whom 11 (1.1%) were confirmed to have hearing loss. In gene screening. AI555G mutation was found in 4 (0.4%) of the 1000 newborns and C1494T mutation was found in 2 (0.2%) infants, though they were all identified as normal in the first-step hearing screening. Conclusions Mitochondria deafness genes screening can complement hearing screening, and may effectively help to avoid later healing loss in children sensitive to aminoglycoside antibiotics.%目的 探讨在新生儿听力筛查同时,采用新生儿脐带血进行线粒体耳聋基因筛查的可行性及其意义.方法 收集邯郸地区新生儿1 000例为研究对象,进行常规听力筛查,同时采集脐带血,用于线粒体DNA的筛查.采用Sanger测序法检测线粒体12S rRNA A1555G和C1494T两个突变位点.结果 在1000名新生儿中,初次听力筛查有141例(14.1%) 未通过,经过复筛后仍有11例 (1.1%) 未通过新生儿听力筛查.线粒体12S rRNA检测发现携带A1555G突变4例(0.4%),C1494T突变2例 (0.2%),而该6例新生儿均通过了初次听力筛查.结论 线粒体耳聋基因筛查可以有效补充听力筛查的不足,早期发现对氨基糖苷类抗生素敏感的个体,避免药物性耳聋的发生.

  4. Neonatal alloimmune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Mella MT

    2015-06-01

    Full Text Available Maria Teresa Mella, Keith A Eddleman Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Mount Sinai School of Medicine, New York, NY, USA Abstract: Neonatal alloimmune thrombocytopenia occurs in one in 1,000–1,500 live births and is the most common cause of severe thrombocytopenia and intracranial hemorrhage in term infants. It is the equivalent of red blood cell alloimmunization and is due to transplacental passage of maternal antibodies against paternally derived fetal platelet antigens. A diagnosis of neonatal alloimmune thrombocytopenia should be considered for any neonate with unexplained thrombocytopenia. Once the diagnosis is made, it is known that all subsequent pregnancies are at risk for severe disease. In order to prevent the devastating and potentially life-threatening manifestations of the disease, the goal is to initiate treatment early with serial percutaneous umbilical blood sampling, intravenous immunoglobulin administration, prednisone, and/or fetal platelet transfusions. Timing of delivery is variable with delivery for severe disease recommended at an earlier gestational age. Vaginal delivery can be considered if the fetal platelet count is greater than 50,000–100,000 µL. Thrombocytopenia due to neonatal alloimmune thrombocytopenia usually resolves spontaneously within 1–2 weeks after delivery, but a platelet transfusion may be necessary to prevent a serious hemorrhagic event. In all cases, a multidisciplinary approach to care should be undertaken with delivery at a tertiary care center. Keywords: neonatal thrombocytopenia, fetal therapy, intracranial hemorrhage, intravenous immunoglobulin, alloimmunization

  5. [Vasopressin V2 receptor-related pathologies: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropiate antidiuresis].

    Science.gov (United States)

    Morin, Denis

    2014-12-01

    Congenital nephrogenic diabetes insipidus is a rare hereditary disease with mainly an X-linked inheritance (90% of the cases) but there are also autosomal recessive and dominant forms. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine. The X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Affected males are often symptomatic in the neonatal period with a lack of weight gain, dehydration and hypernatremia but mild phenotypes may also occur. Females carrying the mutation may be asymptomatic but, sometimes, severe polyuria is found due to the random X chromosome inactivation. The autosomal recessive and dominant forms, occurring in both genders, are linked to mutations in the aquaporin-2 gene. The treatment remains difficult, especially in infants, and is based on a low osmotic diet with increased water intake and the use of thiazides and indomethacin. The main goal is to avoid hypernatremic episodes and maintain a good hydration state. Potentially, specific treatment, in some cases of X-linked congenital nephrogenic diabetes insipidus, with pharmacological chaperones such as non-peptide vasopressin-2 receptor antagonists will be available in the future. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels.

  6. [Diabetes and pregnancy].

    Science.gov (United States)

    Schäfer-Graf, U M; Vetter, K

    1999-10-01

    Preexisting type-I-diabetes (incidence 0.8%) and gestational diabetes (3-5%) are the two manifestations of disturbed carbohydrate metabolism in pregnancy. Maternal hyperglycemia and the resulting excessive glucose supply for the fetus leads to fetal hyperinsulinism which is responsible for the complications in the offspring. The most important clinical manifestations are the excessive growth of the fetus (macrosomia), the risk of intrauterine death and the neonatal morbidity caused by hypoglycemia and the delay of maturation of lungs and liver. Women with type-I-diabetes require preconception counseling and optimizing of glucose control to reduce the rate of abortion and of congenital anomalies of the offspring. Furthermore kidney function and retinopathia should be evaluated preconceptionally. The management of diabetic pregnancies requires a tight cooperation of obstetricians and diabetologists. Blood glucose levels have to be lower than outside pregnancy. Gestational diabetes is diagnosed by a screening test with 50 g glucose for all women followed by a regular 75 g oGTT when the glucose value is > or = 140 mg%. In most of the women euglycemia can be achieved by diet and exercise. Women after pregnancies with gestational diabetes should be retested postnatally and counseled about their increased risk to develop diabetes in later life.

  7. Diabetes mellitus and pregnancy

    Directory of Open Access Journals (Sweden)

    Fathi I Abourawi

    2006-07-01

    Full Text Available Diabetes mellitus is the most common medical complication of pregnancy and it carries a significant risk to the foetus and the mother. Congenital malformations and perinatal morbidity remain common compared with the offspring of non diabetic pregnancies. Diabetic mothers are at risk of progression of micro-vascular diabetic complications as well as early pregnancy loss, pre-eclampsia, polyhydramnios and premature labour. Glycaemic control before and during pregnancy is critical and the benefit may result in a viable, healthy offspring. Gestational diabetes mellitus (GDM which manifests for the first time during pregnancy is common and on the increase, its proper management will reduce the risk of neonatal macrosomia and hypoglycaemia. Post-partum evaluation of glucose tolerance and appropriate counselling in women with GDM may help decrease the high risk of subsequent type 2 diabetes in the long-term. The article will briefly review the changes in the carbohydrate metabolism that characterise normal pregnancy and will focus on a practical approach to the care of patients with pre-existing diabetes as well as GDM.

  8. Diabetes - resources

    Science.gov (United States)

    Resources - diabetes ... The following sites provide further information on diabetes: American Diabetes Association -- www.diabetes.org Juvenile Diabetes Research Foundation International -- www.jdrf.org National Center for Chronic Disease Prevention and Health Promotion -- ...

  9. Diabetic Retinopathy

    Science.gov (United States)

    ... Disease > Facts About Diabetic Eye Disease Facts About Diabetic Eye Disease Points to Remember Diabetic eye disease ... existing therapies for different patient groups. What is diabetic eye disease? Diabetic eye disease can affect many ...

  10. Intraoperative fluid therapy in neonates

    African Journals Online (AJOL)

    aBarts Health NHS Trust, The Royal London Hospital, London, United Kingdom ... Differences from adults and children in physiology and anatomy of neonates inform our ..... this as a reliable monitor for fluid responsiveness in neonates.

  11. The value of neonatal autopsy.

    LENUS (Irish Health Repository)

    Hickey, Leah

    2012-01-01

    Neonatal autopsy rates were in decline internationally at the end of the last century. Our objective was to assess the current value of neonatal autopsy in providing additional information to families and healthcare professionals.

  12. Effects of individualized medical intervention on liquids and neonatal birth weight in pregnant women with gestational diabetes mellitus in late pregnancy%个体化医学干预对妊娠期糖尿病孕妇孕晚期血脂及新生儿出生体重的影响

    Institute of Scientific and Technical Information of China (English)

    吴姝; 韦青; 冯筱; 李磊; 俞力

    2015-01-01

    目的:探讨个体化医学干预对妊娠期糖尿病(GDM )孕妇孕晚期血脂与新生儿出生体重的影响。方法测定GDM孕妇115例(A组)和265例正常孕妇(B组)三酰甘油(TG)、高密度脂蛋白胆固醇(HDL‐C)及低密度脂蛋白胆固醇(LDL‐C)等血脂水平。A组中,40例行个体化医学干预(A1组),75例行门诊随访干预(A2组)。记录新生儿出生体重。结果与B组相比,A2组 T G较高,HDL‐C较低(P<0.05)。A1组 TG和 LDL‐C较B组低(P<0.05)。A2组新生儿出生体重较A1组和B组高(P<0.05)。GDM孕妇TG水平与新生儿出生体重正相关(r=0.42,P<0.05)。结论TG水平与新生儿出生体重之间存在较大关系。个体化医学干预能够改善GDM 孕妇孕晚期的血脂水平、降低新生儿出生体重。%Objective To explore the effects of individualized medicalized intervention on maternal liquids and neonatal birth weight in pregnant women with gestational diabetes mellitus (GDM ) in late pregnancy .Methods Plasma levels of triglyceride (TG ) ,high density lipoprotein cholesterol(HDL‐C) and low density lipoprotein cholesterol(LDL‐C) in late pregnancy were detected in 115 pregnant women with GDM (group A) and 75 women with normal pregnancy(group B) .Of group A ,40 cases(group A1) were treated with individualized medical intervention and 75 cases(group A2) treated with outpatient follow‐up intervention .The neonatal birth weights were recorded .Results TG was higher ,but HDL‐C was lower ,in group A2 than those in group B(P<0 .05) .TG and LDL‐C were lower in group A1 than those in group B(P<0 .05) .The neonatal birth weight was lower in groups of A1 and B than that in group A2(P<0 .05) .There was a positive correlation between TG and neonatal birth weight in group A (r=0 .42 ,P<0 .05) .Conclusion Neonatal birth weight is closely related to TG in late pregnancy .The individualized medical intervention

  13. Fructosamine levels and hyperglycemia in preterm neonates.

    Science.gov (United States)

    Gyarmati, Judit; Tokes-Fuzesi, Margit; Kovacs, Gabor L; Gaal, Valeria; Vida, Gabriella; Ertl, Tibor

    2009-01-01

    Hyperglycemia is a common complication of prematurity, which requires attention because of its high prevalence and multiple consequences. Serum fructosamine used in diabetic patients provides information about the average glucose concentration in the preceding period of 2-3 weeks. We investigated the physiologic characteristics of a glycemic marker, fructosamine, in preterm and term neonates. We also studied its association with hyperglycemia and related morbidities of preterm infants. Fructosamine levels of 22 extremely premature (gestational age, GA: 25.8 +/- 1.0 weeks), 36 moderately premature (GA: 29.8 +/- 1.3 weeks) and 26 term infants (GA: 39.1 +/- 1.3 weeks) were determined in the 1st week of life. Fructosamine assay was repeated in all preterm neonates in the 4th and 7th postnatal weeks. Hyperglycemic episodes and main morbidities of preterm infants were recorded and analyzed in association with fructosamine levels. Preterm infants had higher fructosamine levels after birth compared to term infants and a postnatal fall was observed. Serum fructosamine did not show association with the occurrence of hyperglycemia or its main morbidities in preterm infants. In the framework of our study, we could not confirm the usefulness of fructosamine determination in the glycemic control of preterm neonates during the perinatal period. (c) 2008 S. Karger AG, Basel.

  14. Hiperbilirrubinemia neonatal agravada Aggravated neonatal hyperbilirubinemia

    OpenAIRE

    Ana Campo González; Rosa María Alonso Uría; Rafael Amador Morán; Irka Ballesté López; Rosa Díaz Aguilar; Mercedes Remy Pérez

    2010-01-01

    INTRODUCCIÓN. La mayoría de las veces la ictericia en el recién nacido es un hecho fisiológico, causado por una hiperbilirrubinemia de predominio indirecto, secundario a inmadurez hepática e hiperproducción de bilirrubina. El objetivo de este estudio fue determinar el comportamiento de la hiperbilirrubinemia neonatal en el Hospital Docente Ginecoobstétrico de Guanabacoa en los años 2007 a 2009. MÉTODOS. Se realizó un estudio descriptivo y retrospectivo de 173 recién nacidos que ingresaron al ...

  15. Treatment of pediatric diabetes mellitus%儿童糖尿病的治疗

    Institute of Scientific and Technical Information of China (English)

    包美珍

    2008-01-01

    儿童糖尿病的治疗包括饮食控制、体育锻炼、药物治疗、防治并发症及糖尿病教育.胰岛素的用量对新患者及糖尿病酮症酸中毒者有所不同,二甲双胍对2型糖尿病患儿最合适.新生儿糖尿病患者根据突变基因不同而给予磺脲类药物或胰岛素治疗.%Treatment of pediatric diabetes mellitus includes:diet control,exercise,drug therapy,prevention of complications and diabetic education.Insulin dosage is different for new patients and DKA,metformin is the choice of type 2 diabetic children.Treatment of neonatal diabetes is diffenrent according to different gene mutation:sulfonylurea or insulin.

  16. Neonatal brucellosis: A case report.

    Science.gov (United States)

    Alnemri, Abdul Rahman M; Hadid, Adnan; Hussain, Shaik Asfaq; Somily, Ali M; Sobaih, Badr H; Alrabiaah, Abdulkarim; Alanazi, Awad; Shakoor, Zahid; AlSubaie, Sarah; Meriki, Naema; Kambal, Abdelmageed M

    2017-02-28

    Although brucellosis is not uncommon in Saudi Arabia, neonatal brucellosis has been infrequently reported. In this case of neonatal brucellosis, Brucella abortus was isolated by blood culture from both the mother and the neonate. Serology was positive only in the mother.

  17. The impact of SLCO1B1 genetic polymorphisms on neonatal hyperbilirubinemia: a systematic review with meta-analysis.

    Science.gov (United States)

    Liu, Jiebo; Long, Jun; Zhang, Shaofang; Fang, Xiaoyan; Luo, Yuyuan

    2013-01-01

    To determine whether three variants (388 G>A, 521 T>C, and 463 C>A) of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) are associated with neonatal hyperbilirubinemia. The China National Knowledge Infrastructure and MEDLINE databases were searched. The systematic review with meta-analysis included genetic studies which assessed the association between neonatal hyperbilirubinemia and 388 G>A, 521 T>C, and 463 C>A variants of SLCO1B1 between January of 1980 and December of 2012. Data selection and extraction were performed independently by two reviewers. Ten articles were included in the study. The results revealed that SLCO1B1 388 G>A is associated with an increased risk of neonatal hyperbilirubinemia (OR, 1.39; 95% CI, 1.07-1.82) in Chinese neonates, but not in white, Thai, Latin American, or Malaysian neonates. The SLCO1B1 521 T>C mutation showed a low risk of neonatal hyperbilirubinemia in Chinese neonates, while no significant associations were found in Brazilian, white, Asian, Thai, and Malaysian neonates. There were no significant differences in SLCO1B1 463 C>A between the hyperbilirubinemia and the control group. This study demonstrated that the 388 G>A mutation of the SLCO1B1 gene is a risk factor for developing neonatal hyperbilirubinemia in Chinese neonates, but not in white, Thai, Brazilian, or Malaysian populations; the SLCO1B1 521 T>C mutation provides protection for neonatal hyperbilirubinemia in Chinese neonates, but not in white, Thai, Brazilian, or Malaysian populations. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  18. Rings in the neonate.

    LENUS (Irish Health Repository)

    Hackett, C B

    2011-02-01

    Neonatal lupus erythematosus (NLE) is an uncommon disease of the neonate. It is believed to be caused by the transplacental passage of maternal autoantibodies to the ribonucleoproteins (Ro\\/SSA, La\\/SSB or rarely U RNP) as these are almost invariably present in NLE sera. The most common clinical manifestations include cutaneous lupus lesions and congenital complete heart block. Hepatobiliary and haematologic abnormalities are reported less frequently. We describe a patient with cutaneous NLE to illustrate and raise awareness of the characteristic annular eruption of this condition. We also emphasize the need for thorough investigation for concomitant organ involvement and for maternal education regarding risk in future pregnancies.

  19. Ultrasonography of Neonatal Cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Jung Eun [Seoul National University Hospital, Seoul (Korea, Republic of)

    2012-06-15

    Ultrasonography (US) is as an important tool for differentiation of obstructive and non-obstructive causes of jaundice in infants and children. Beyond two weeks of age, extrahepatic biliary atresia and neonatal hepatitis are the two most common causes of persistent neonatal jaundice: differentiation of extrahepatic biliary atresia, which requires early surgical intervention, is very important. Meticulous analysis should focus on size and configuration of the gallbladder and anatomical changes of the portahepatis. In order to narrow the differential diagnosis, combined approaches using hepatic scintigraphy, MR cholangiography, and, at times, percutaneous liver biopsy are necessary. US is useful for demonstrating choledochal cyst, bile plug syndrome, and spontaneous perforation of the extrahepatic bile duct

  20. Truncating Homozygous Mutation of Carboxypeptidase E (CPE in a Morbidly Obese Female with Type 2 Diabetes Mellitus, Intellectual Disability and Hypogonadotrophic Hypogonadism.

    Directory of Open Access Journals (Sweden)

    Suzanne I M Alsters

    Full Text Available Carboxypeptidase E is a peptide processing enzyme, involved in cleaving numerous peptide precursors, including neuropeptides and hormones involved in appetite control and glucose metabolism. Exome sequencing of a morbidly obese female from a consanguineous family revealed homozygosity for a truncating mutation of the CPE gene (c.76_98del; p.E26RfsX68. Analysis detected no CPE expression in whole blood-derived RNA from the proband, consistent with nonsense-mediated decay. The morbid obesity, intellectual disability, abnormal glucose homeostasis and hypogonadotrophic hypogonadism seen in this individual recapitulates phenotypes in the previously described fat/fat and Cpe knockout mouse models, evidencing the importance of this peptide/hormone-processing enzyme in regulating body weight, metabolism, and brain and reproductive function in humans.

  1. An emerging, recognizable facial phenotype in association with mutations in GLI-similar 3 ( GLIS3 )

    OpenAIRE

    Dimitri, P.; Franco, E; Habeb, A. M.; Gurbuz, F.; Moussa, K.; Taha, D.; Wales, J.K.H.; Hogue, J.; Slavotinek, A.; Shetty, A; M. Balasubramanian

    2016-01-01

    Neonatal diabetes and hypothyroidism (NDH) syndrome was first described in 2003 in a consanguineous Saudi Arabian family where two out of four siblings were reported to have presented with proportionate IUGR, neonatal non-autoimmune diabetes mellitus, severe congenital hypothyroidism, cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterised by enlarged kidneys and multiple small cysts with deficient cortico-med...

  2. Cytolipotoxicity-induced involution of the female reproductive tract following expression of obese (ob/ob) and diabetes (db/db) genotype mutations: progressive, hyperlipidemic transformation into adipocytic tissues.

    Science.gov (United States)

    Garris, David R; Garris, Bryan L

    2004-01-01

    Both diabetes (db/db) and obese (ob/ob) single gene mutations induce a progressive, hyperglycemic-hyperinsulinemic endometabolic environment which promotes hypercytolipidemic, utero-ovarian involution in C57BL/KsJ mice. The progressive expression of the induced diabetes-obesity syndrome (DOS) results in female reproductive sterility and eventual organoatrophy. In order to define the intra-cytoplasmic alterations induced by the progressive cytolipidemia on cellular vitality, utero-ovarian tissue samples were collected from both control (+/?) and littermate-matched ob/ob or db/db C57BL/KsJ mice at either 4 weeks (initial-onset DOS phase), 8 weeks (progressive, overt DOS phase), or 16 weeks (chronic-DOS phase) of age for cytolipid distribution analysis. All db/db and ob/ob mutant groups exhibited phenotypic obesity and systemic hyperglycemia-hyperinsulinemia relative to age-matched littermate +/? groups. In all db/db and ob/ob age groups, a progressive hypercytolipidemia was noted relative to +/? groups. When analyzed for lipid channeling, a progressive perinuclear mapping pattern of cytolipid distribution was noted. The primary locus of initial db/db and ob/ob cytolipid deposition was localized to the baso-polar regions in endometrial epithelia samples, or to the interstitium-thecal layer border of ovarian follicular compartments, during the initial-onset DOS phase. Progressively, intra-cytoplasmic lipid mobilization promoted a consistent perinuclear channeling of lipid vacuoles, ultimately isolating nuclear loci from the peripherally displaced cytoplasmic organelles within uterine epithelial layers. In db/db and ob/ob ovarian tissue samples, a progressive, gradient-related lipid infiltration of interstitial, thecal and, ultimately, granulosa cell layers promoted an enhanced rate of follicular-lipidemic atresia relative to +/? groups. In each tissue layer, the cytolipidemia promoted a dramatic perinuclear lipid-isolation barrier from intra-cytoplasmic organelle

  3. Pharmacogenomics in diabetes mellitus

    DEFF Research Database (Denmark)

    Zhou, Kaixin; Pedersen, Helle Krogh; Dawed, Adem Y.

    2016-01-01

    Genomic studies have greatly advanced our understanding of the multifactorial aetiology of type 2 diabetes mellitus (T2DM) as well as the multiple subtypes of monogenic diabetes mellitus. In this Review, we discuss the existing pharmacogenetic evidence in both monogenic diabetes mellitus and T2DM....... We highlight mechanistic insights from the study of adverse effects and the efficacy of antidiabetic drugs. The identification of extreme sulfonylurea sensitivity in patients with diabetes mellitus owing to heterozygous mutations in HNF1A represents a clear example of how pharmacogenetics can direct...... future pharmacogenomic findings could provide insights into treatment response in diabetes mellitus that, in addition to other areas of human genetics, facilitates drug discovery and drug development for T2DM....

  4. Clinical characteristics of diabetes with mitochondrial tRNA Leu(UUR) gene 3243 A to G mutation%线粒体tRNALeu(UUR)基因A3243G突变糖尿病患者的临床特征

    Institute of Scientific and Technical Information of China (English)

    杨篷; 张曼娜; 盛春君; 李妍; 周娇娇; 崔文洁; 曲伸

    2015-01-01

    目的:探讨线粒体tRNALeu(UUR)基因A3243G突变糖尿病患者的临床特征。方法选取临床症状疑似线粒体基因突变糖尿病患者12例,采外周血提取DNA ,检测mtDNA 3243A→G点突变情况。结果共4例携带mtDNA 3243A→G点突变,均存在线粒体基因突变糖尿病的典型临床表现,即起病年龄早、体型消瘦、伴严重双耳听力损害、胰岛β细胞分泌功能降低及无明显母系遗传史。在测定骨密度的3例患者中,2例骨质疏松,1例骨密度降低。结论线粒体基因突变糖尿病患者存在一定的隐匿性,对消瘦、耳聋的年轻患者进行线粒体基因突变筛查及骨代谢评估,有利于及时诊治线粒体基因突变糖尿病患者,防止并发症发生。%Objective To investigate the clinical characteristics of diabetic patients with mitochondrial DNA (mtDNA ) mt3243A → G mutation. Methods Twelve suspected mitochondrial diabetic patients were recruited. The gene fragment was produced by PCR ,and mutation was detected by direct sequencing. Results Four of twelve suspected mtDNA diabetic patients carried mt 3243A → G mutation. All four patients had classic clinical features of mitochondrial DNA diabetes ,including diabetes in early age ,low BMI ,deafness ,and impairedβcell function ,but without significant maternal inheritance. Furthermore ,two of three patients were diagnosed as severe osteoporosis ,and one was diagnosed as reduced bone mineral density. Conclusion Screening the mitochondrial gene mutation in the diabetes patients with lean and deafness can improve the diagnostic rate. Clinicians should pay attention to abnormal bone metabolism in the patients with mitochondrial diabetes.

  5. Neonatal Sepsis and Neutrophil Insufficiencies

    Science.gov (United States)

    Melvan, John Nicholas; Bagby, Gregory J.; Welsh, David A.; Nelson, Steve; Zhang, Ping

    2011-01-01

    Sepsis has continuously been a leading cause of neonatal morbidity and mortality despite current advances in chemotherapy and patient intensive care facilities. Neonates are at high risk for developing bacterial infections due to quantitative and qualitative insufficiencies of innate immunity, particularly granulocyte lineage development and response to infection. Although antibiotics remain the mainstay of treatment, adjuvant therapies enhancing immune function have shown promise in treating sepsis in neonates. This chapter reviews current strategies for the clinical management of neonatal sepsis and analyzes mechanisms underlying insufficiencies of neutrophil defense in neonates with emphasis on new directions for adjuvant therapy development. PMID:20521927

  6. What neonatal complications should the pediatrician beaware of in case of maternal gestational diabetes?

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    In the epidemiologic context of maternal obesity andtype 2 diabetes (T2D), the incidence of gestationaldiabetes has significantly increased in the last decades.Infants of diabetic mothers are prone to variousneonatal adverse outcomes, including metabolic andhematologic disorders, respiratory distress, cardiacdisorders and neurologic impairment due to perinatalasphyxia and birth traumas, among others. Macrosomiais the most constant consequence of diabetes andits severity is mainly influenced by maternal bloodglucose level. Neonatal hypoglycemia is the mainmetabolic disorder that should be prevented as soonas possible after birth. The severity of macrosomia andthe maternal health condition have a strong impacton the frequency and the severity of adverse neonataloutcomes. Pregestational T2D and maternal obesitysignificantly increase the risk of perinatal death and birthdefects. The high incidence of maternal hyperglycemiain developing countries, associated with the scarcityof maternal and neonatal care, seriously increase theburden of neonatal complications in these countries.

  7. Multiple arrhythmic syndromes in a newborn, owing to a novel mutation in SCN5A

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Schmitt, Nicole; Grubb, Søren

    2011-01-01

    Mutations in the SCN5A gene have been linked to Brugada syndrome (BrS), conduction disease, Long QT syndrome (LQT3), atrial fibrillation (AF), and to pre- and neonatal ventricular arrhythmias.......Mutations in the SCN5A gene have been linked to Brugada syndrome (BrS), conduction disease, Long QT syndrome (LQT3), atrial fibrillation (AF), and to pre- and neonatal ventricular arrhythmias....

  8. blood in neonates

    African Journals Online (AJOL)

    From the total of 548 male and 659 female neonates 10.2% males and 8% females had TSI-I ... congenital hypothyroidism (CH) in the Ethiopia situation where hospital discharges are within 24 ... counting weeks of pregnancy from the first day.

  9. Neonatal typhoid fever.

    OpenAIRE

    Chin, K C; Simmonds, E J; Tarlow, M J

    1986-01-01

    Three infants of Pakistani immigrant mothers developed typhoid fever in the neonatal period. All three survived, but two became chronic excretors of Salmonella typhi. The risk of an outbreak of typhoid fever in a maternity unit or special care baby unit is emphasized.

  10. Fatal neonatal parechovirus encephalitis

    NARCIS (Netherlands)

    A.L. van Zwol (Arjen); M.H. Lequin (Maarten); C.D. Tesselaar (Coranne); A.A. Eijck (Annemiek); G.J.A. Driessen (Gertjan); M. de Hoog (Matthijs); P. Govaert (Paul)

    2009-01-01

    textabstractTwo infants developed encephalitis in the late neonatal period due to human parechovirus type 3 (HPeV-3). This finally resulted in intractable seizures leading to death. Both presented with classical signs and symptoms. HPeV-3 was detected in nasopharyngeal and rectal swabs,

  11. Design and rationale of a large, international, prospective cohort study to evaluate the occurrence of malformations and perinatal/neonatal death using insulin detemir in pregnant women with diabetes in comparison with other long-acting insulins

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R; Andersen, Henning; Kring, Sofia I I

    2017-01-01

    in the context of routine practice. The primary endpoint is the proportion of pregnancies in women treated with insulin detemir, compared with other basal insulin regimens, which do not result in any of the following events: major congenital malformations, perinatal death or neonatal death. A sample size of 3075...... pregnancies was calculated to provide an 80% power to detect a difference of 3.5% between groups in the primary endpoint at a 5% level. DISCUSSION: The study will also examine other important maternal endpoints (e.g., incidences of severe hypoglycaemia and pre-eclampsia) and perinatal outcomes...

  12. Risk of hearing loss in small for gestational age neonates

    Directory of Open Access Journals (Sweden)

    Melani Rakhmi Mantu

    2011-01-01

    Full Text Available Background Small for gestational age (SGA neonates often have intrauterine growth restriction due to placental insufficiency and chronic hypoxia. These conditions may cause developmental impairment, psychosocial disabilities, or metabolic dysfunction in later life. Previous studies have shown greater incidence of speech and language disabilities, learning impairment, and ncuromotor dysfunction in term SGA infants compared to term appropriate for gestational age (AGA infants. Objective To compare hearing loss in SGA and AGA neonates using otoacoustic emission (OAE tests and to study correlations between maternal risk factors and hearing loss in SGA neonates. Methods A cross-sectional study was performed in St. Borromeus Hospital, Limijati Hospital, and Melinda Hospital in Bandung from February to May 2010. Study subjects consisted of full-term neonates born in these three hospitals. A retrospective medical record review was performed for this Study. Statistical analysis was done by multivariable logistic-regression. Results There was a total of 4279 subjects in our study, including 100 SGA neonates and 4179 AGA neonates. We observed a greater percentage of OAE 'refer' (indicating abnormal OAE results in the SGA group compared to the AGA group (P<0.001, Z=1.3.247. For subjects with OAE ,refer' results, we also analyzed the correlation to the following maternal risk factors: smoking, hypertension, diabetes mellitus and asthma. We also found significant differences between those with and without each of the four maternal risk factors studied (P<0.001. By using multivariant analysis to compare SGA and AGA neonates, we found the odds ratio (OR to be 4.34 (95% CI 2.52 to'7.49, P = 0.001, meaning the SGA group had a 4.34 times higher risk of hearing loss than the AGA group. Conclusion SGA neonates had a higher risk of hearing loss than A(3A neonates. In addition, maternal smoking, hypertension, diabetes mellitus and asthma significantly correlated to

  13. Telemedicine in Neonatal Home Care

    DEFF Research Database (Denmark)

    Holm, Kristina Garne; Brødsgaard, Anne; Zachariassen, Gitte

    2016-01-01

    visits from neonatal nurses. For hospitals covering large regions, home visits may be challenging, time consuming, and expensive and alternative approaches must be explored. OBJECTIVE: To identify parental needs when wanting to provide neonatal home care supported by telemedicine. METHODS: The study used...... participatory design and qualitative methods. Data were collected from observational studies, individual interviews, and focus group interviews. Two neonatal units participated. One unit was experienced in providing neonatal home care with home visits, and the other planned to offer neonatal home care...... with the neonatal unit, and (4) an online knowledge base on preterm infant care, breastfeeding, and nutrition. CONCLUSIONS: Our findings highlight the importance of neonatal home care. NH provides parents with a feeling of being a family, supports their self-efficacy, and gives them a feeling of security when...

  14. [Recommendations for neonatal transport].

    Science.gov (United States)

    Moreno Hernando, J; Thió Lluch, M; Salguero García, E; Rite Gracia, S; Fernández Lorenzo, J R; Echaniz Urcelay, I; Botet Mussons, F; Herranz Carrillo, G; Sánchez Luna, M

    2013-08-01

    During pregnancy, it is not always possible to identify maternal or foetal risk factors. Infants requiring specialised medical care are not always born in centres providing intensive care and will need to be transferred to a referral centre where intensive care can be provided. Therefore Neonatal Transport needs to be considered as part of the organisation of perinatal health care. The aim of Neonatal Transport is to transfer a newborn infant requiring intensive care to a centre where specialised resources and experience can be provided for the appropriate assessment and continuing treatment of a sick newborn infant. Intrauterine transfer is the ideal mode of transport when the birth of an infant with risk factors is diagnosed. Unfortunately, not all problems can be detected in advance with enough time to safely transfer a pregnant woman. Around 30- 50% of risk factors will be diagnosed during labour or soon after birth. Therefore, it is important to have the knowledge and resources to resuscitate and stabilise a newborn infant, as well as a specialised neonatal transport system. With this specialised transport it is possible to transfer newly born infants with the same level of care that they would receive if they had been born in a referral hospital, without increasing their risks or affecting the wellbeing of the newborn. The Standards Committee of the Spanish Society of Neonatology reviewed and updated recommendations for intrauterine transport and indications for neonatal transfer. They also reviewed organisational and logistic factors involved with performing neonatal transport. The Committee review included the type of personnel who should be involved; communication between referral and receiving hospitals; documentation; mode of transport; equipment to stabilise newly born infants; management during transfer, and admission at the referral hospital.

  15. Profound neonatal hypoglycemia and lactic acidosis caused by pyridoxine-dependent epilepsy.

    Science.gov (United States)

    Mercimek-Mahmutoglu, Saadet; Horvath, Gabriella A; Coulter-Mackie, Marion; Nelson, Tanya; Waters, Paula J; Sargent, Michael; Struys, Eduard; Jakobs, Cornelis; Stockler-Ipsiroglu, Sylvia; Connolly, Mary B

    2012-05-01

    Pyridoxine-dependent epilepsy (PDE) was first described in 1954. The ALDH7A1 gene mutations resulting in α-aminoadipic semialdehyde dehydrogenase deficiency as a cause of PDE was identified only in 2005. Neonatal epileptic encephalopathy is the presenting feature in >50% of patients with classic PDE. We report the case of a 13-month-old girl with profound neonatal hypoglycemia (0.6 mmol/L; reference range >2.4), lactic acidosis (11 mmol/L; reference range pyridoxine. The diagnosis of α-aminoadipic semialdehyde dehydrogenase deficiency was confirmed based on the elevated urinary α-aminoadipic semialdehyde excretion, compound heterozygosity for a known splice mutation c.834G>A (p.Val278Val), and a novel putative pathogenic missense mutation c.1192G>C (p.Gly398Arg) in the ALDH7A1 gene. She has been seizure-free since 1.5 months of age on treatment with pyridoxine alone. She has motor delay and central hypotonia but normal language and social development at the age of 13 months. This case is the first description of a patient with PDE due to mutations in the ALDH7A1 gene who presented with profound neonatal hypoglycemia and lactic acidosis masquerading as a neonatal-onset gluconeogenesis defect. PDE should be included in the differential diagnosis of hypoglycemia and lactic acidosis in addition to medically refractory neonatal seizures.

  16. Gain-of-function mutations in the K(ATP channel (KCNJ11 impair coordinated hand-eye tracking.

    Directory of Open Access Journals (Sweden)

    James S McTaggart

    Full Text Available Gain-of-function mutations in the ATP-sensitive potassium channel can cause permanent neonatal diabetes mellitus (PNDM or neonatal diabetes accompanied by a constellation of neurological symptoms (iDEND syndrome. Studies of a mouse model of iDEND syndrome revealed that cerebellar Purkinje cell electrical activity was impaired and that the mice exhibited poor motor coordination. In this study, we probed the hand-eye coordination of PNDM and iDEND patients using visual tracking tasks to see if poor motor coordination is also a feature of the human disease.Control participants (n = 14, patients with iDEND syndrome (n = 6 or 7, and patients with PNDM (n = 7 completed three computer-based tasks in which a moving target was tracked with a joystick-controlled cursor. Patients with PNDM and iDEND were being treated with sulphonylurea drugs at the time of testing.No differences were seen between PNDM patients and controls. Patients with iDEND syndrome were significantly less accurate than controls in two of the three tasks. The greatest differences were seen when iDEND patients tracked blanked targets, i.e. when predictive tracking was required. In this task, iDEND patients incurred more discrepancy errors (p = 0.009 and more velocity errors (p= 0.009 than controls.These results identify impaired hand-eye coordination as a new clinical feature of iDEND. The aetiology of this feature is likely to involve cerebellar dysfunction. The data further suggest that sulphonylurea doses that control the diabetes of these patients may be insufficient to fully correct their neurological symptoms.

  17. Microencapsulated neonatal porcine islet transplantation reverses the morphological changes of thyroids in diabetic rats%微囊包膜新生猪胰岛移植逆转糖尿病大鼠甲状腺形态学改变

    Institute of Scientific and Technical Information of China (English)

    李佐强; 刘纯; 何军; 舒昌达

    1999-01-01

    Objective To investigate the morphological changes of the thyroids in diabetic rats undergoing the transplantation of microencapsulated neonatal porcine islets. Methods 800 microencapsulated neonatal porcine islets were transplanted intraperitoneally into streptozotocin-induced diabetic rats. Three months after the islet transplantation, all animals were killed, and the thyroid sections were observed. Results The levels of plasma glucose(PG) were (4.87 ± 0.47)mmol/L in control group (CG) and (6.44 ± 1.82)mmol/L in transplantation group (TG), and (16.12 ± 1.47)mmol/L in diabetes group (DG) before decapitation of the animals. No significant difference was found in PG between TG and CG( P >0.05), but the difference in PG between DG and CG was significant (P < 0. 001 ). The colloid areas in the follicular lumens of the thyroids in TG and DG showed no significant difference as compared with those in CG, but the cell heights of the follicular epithelium of the thyroids (CHFET) in DG had a significant difference as compared with those in CG (P < 0. 001 ), whereas no significant difference was observed in CHFET between TG and CG (P > 0.05 ). Conclusion The morphological change of the epithelial cells of the thyroid follicle in the recipients may be reversed if its PG was effectively controlled after islet transplantation, which may contribute to reversing the thyroid hyposecretion function in diabetes mellitus.%目的 探讨糖尿病大鼠胰岛移植后的甲状腺形态学的变化.方法 给用链脲霉素所致的糖尿病大鼠腹腔内移植微囊包膜的新生猪胰岛800个.术后3个月将动物处死,取甲状腺切片观察.结果 动物处死前对照组及移植组的血糖水平分别为(4.87±0.47)mmol/L和(6.44±1.82)mmol/L,糖尿病组为(16.12±1.47)mmol/L,移植组与对照组比较,差异不显著(P>0.05),糖尿病组与对照组比较,差异显著(P<0.001);甲状腺滤泡腔内胶质的面积,移植组、糖尿病组分别与对照组

  18. Neonatal compartment syndrome.

    Science.gov (United States)

    Martin, B; Treharne, L

    2016-09-01

    A term neonate was born with a grossly swollen and discoloured left hand and forearm. He was transferred from the local hospital to the plastic surgical unit, where a diagnosis of compartment syndrome was made and he underwent emergency forearm fasciotomies at six hours of age. Following serial debridements of necrotic tissue, he underwent split-thickness skin grafting of the resultant defects of his forearm, hand and digits. At the clinic follow-up appointment two months after the procedure, he was found to have developed severe flexion contractures despite regular outpatient hand therapy and splintage. He has had further reconstruction with contracture release, use of artificial dermal matrix, and K-wire fixation of the thumb and wrist. Despite this, the long term outcome is likely to be an arm with poor function. The key learning point from this case is that despite prompt transfer, diagnosis and appropriate surgical management, the outcome for neonatal compartment syndrome may still be poor.

  19. A frequent splicing mutation and novel missense mutations color the updated mutational spectrum of classic galactosemia in Portugal.

    Science.gov (United States)

    Coelho, Ana I; Ramos, Ruben; Gaspar, Ana; Costa, Cláudia; Oliveira, Anabela; Diogo, Luísa; Garcia, Paula; Paiva, Sandra; Martins, Esmeralda; Teles, Elisa Leão; Rodrigues, Esmeralda; Cardoso, M Teresa; Ferreira, Elena; Sequeira, Sílvia; Leite, Margarida; Silva, Maria João; de Almeida, Isabel Tavares; Vicente, João B; Rivera, Isabel

    2014-01-01

    Classic galactosemia is an autosomal recessive disorder caused by deficient galactose-1-phosphate uridylyltransferase (GALT) activity. Patients develop symptoms in the neonatal period, which can be ameliorated by dietary restriction of galactose. Many patients develop long-term complications, with a broad range of clinical symptoms whose pathophysiology is poorly understood. The high allelic heterogeneity of GALT gene that characterizes this disorder is thought to play a determinant role in biochemical and clinical phenotypes. We aimed to characterize the mutational spectrum of GALT deficiency in Portugal and to assess potential genotype-phenotype correlations. Direct sequencing of the GALT gene and in silico analyses were employed to evaluate the impact of uncharacterized mutations upon GALT functionality. Molecular characterization of 42 galactosemic Portuguese patients revealed a mutational spectrum comprising 14 nucleotide substitutions: ten missense, two nonsense and two putative splicing mutations. Sixteen different genotypic combinations were detected, half of the patients being p.Q188R homozygotes. Notably, the second most frequent variation is a splicing mutation. In silico predictions complemented by a close-up on the mutations in the protein structure suggest that uncharacterized missense mutations have cumulative point effects on protein stability, oligomeric state, or substrate binding. One splicing mutation is predicted to cause an alternative splicing event. This study reinforces the difficulty in establishing a genotype-phenotype correlation in classic galactosemia, a monogenic disease whose complex pathogenesis and clinical features emphasize the need to expand the knowledge on this "cloudy" disorder.

  20. Telemedicine in Neonatal Home Care

    DEFF Research Database (Denmark)

    Garne, Kristina; Brødsgaard, Anne; Zachariassen, Gitte;

    2016-01-01

    BACKGROUND: For the majority of preterm infants, the last weeks of hospital admission mainly concerns tube feeding and establishment of breastfeeding. Neonatal home care (NH) was developed to allow infants to remain at home for tube feeding and establishment of breastfeeding with regular home...... visits from neonatal nurses. For hospitals covering large regions, home visits may be challenging, time consuming, and expensive and alternative approaches must be explored. OBJECTIVE: To identify parental needs when wanting to provide neonatal home care supported by telemedicine. METHODS: The study used...... participatory design and qualitative methods. Data were collected from observational studies, individual interviews, and focus group interviews. Two neonatal units participated. One unit was experienced in providing neonatal home care with home visits, and the other planned to offer neonatal home care...

  1. Anorectal malformations in neonates

    Directory of Open Access Journals (Sweden)

    Bilal Mirza

    2011-01-01

    Full Text Available Background : Anorectal malformations (ARM are associated with congenital anomalies and other risk factors, yielding a poor prognosis, especially in neonatal life. Objectives: This study was performed to identify the congenital anomalies as a factor of poor prognosis (mortality in such patients. Settings: Department of Pediatric surgery, The Children′s Hospital and The Institute of Child Health, Lahore. Design: Prospective observational study, with statistical support. Materials and Methods: The information on the demography, clinical features, investigations, management performed, and outcome was entered in the designed proforma and analysed with the help of statistical software EpiInfo version 3.5.1. Statistical test: Chi-square test was used to determine statistical significance of the results. Results : Of 100 neonates with ARM, 77 were male and 23, female (3.4:1. The mean age at presentation was 3.4 days (range, 12 hrs to 28 days. In 60 patients (60%, the presentation was imperforate anus without a clinically identified fistula. In 28 patients (28%, associated anomalies were present. The common associated anomalies were urogenital (10%, cardiovascular (8%, and gastrointestinal (6%. Down′s syndrome was present in 8 (8% patients. A total of 15 (15% deaths occurred in this study. In patients having associated congenital anomalies, 11 deaths occurred, whereas, 4 deaths were in patients without associated anomalies (P < 0.5. Conclusion : The mortality is higher in neonates with ARM having associated congenital anomalies.

  2. Congenital hypothyroidism in neonates

    Directory of Open Access Journals (Sweden)

    Aneela Anjum

    2014-01-01

    Full Text Available Context: Congenital hypothyroidism (CH is one of the most common preventable causes of mental retardation in children and it occurs in approximately 1:2,000-1:4,000 newborns. Aims and Objectives: The aim of this study is to determine the frequency of CH in neonates. Settings and Design: This cross-sectional study was conducted in neonatal units of the Department of Pediatrics Unit-I, King Edward Medical University/Mayo Hospital, Lahore and Lady Willington Hospital Lahore in 6 months (January-June 2011. Materials and Methods: Sample was collected by non-probability purposive sampling. After consent, 550 newborn were registered for the study. Demographic data and relevant history was recorded. After aseptic measures, 2-3 ml venous blood analyzed for thyroid-stimulating hormone (TSH level by immunoradiometric assay. Treatment was started according to the individual merit as per protocol. Statistical Analysis Used: Data was analyzed by SPSS 17 and Chi-square test was applied to find out the association of CH with different variables. Results: The study population consisted of 550 newborns. Among 550 newborns, 4 (0.8% newborns had elevated TSH level. CH had statistically significant association with mother′s hypothyroidism (P value 0.000 and mother′s drug intake during the pregnancy period (P value 0.013. Conclusion: CH is 0.8% in neonates. It has statistically significant association with mother′s hypothyroidism and mother′s drug intake during pregnancy.

  3. Neonatal cardiovascular physiology.

    Science.gov (United States)

    Hines, Michael H

    2013-11-01

    The pediatric surgeon deals with a large number and variety of congenital defects in neonates that frequently involve early surgical intervention and care. Because the neonatal cardiac physiology is unique, starting with the transition from fetal circulation and including differences in calcium metabolism and myocardial microscopic structure and function, it serves the pediatric surgeon well to have a sound understanding of these principles and how they directly and indirectly affect their plans and treatments. In addition, many patients will have associated congenital heart disease that can also dramatically influence not only the surgical and anesthetic care but also the timing and planning of procedures. Finally, the pediatric surgeon is often called upon to treat conditions and complications associated with complex congenital heart disease such as feeding difficulties, bowel perforations, and malrotation in heterotaxy syndromes. In this article, we will review several unique aspects of neonatal cardiac physiology along with the basic physiology of the major groups of congenital heart disease to better prepare the training and practicing pediatric surgeon for care of these complex and often fragile patients.

  4. Women and Diabetes -- Diabetes Medicines

    Science.gov (United States)

    ... Audience For Women Women's Health Topics Women and Diabetes - Diabetes Medicines Share Tweet Linkedin Pin it More sharing ... 1-800-332-1088 to request a form. Diabetes Medicines The different kinds of diabetes medicines are ...

  5. Clinical and laboratory characteristics of neonatal hypocalcemia

    National Research Council Canada - National Science Library

    Cho, Won Im; Yu, Hyeoh Won; Chung, Hye Rim; Shin, Choong Ho; Yang, Sei Won; Choi, Chang Won; Kim, Beyong Il

    2015-01-01

    To describe the clinical characteristics of full-term neonates with hypocalcemia and to suggest factors associated with neonatal hypocalcemia The medical records of full-term neonates with hypocalcemia were reviewed...

  6. Presentation of Neonatal Sinovenous Thrombosis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-09-01

    Full Text Available Signs, risk factors, comorbidities, and radiographic findings in 59 neonates presenting with sinovenous thrombosis are reported from Indiana University School of Medicine, Indianapolis, IN.

  7. Neonatal cystic fibrosis screening test

    Science.gov (United States)

    Cystic fibrosis screening - neonatal; Immunoreactive trypsinogen; IRT test; CF - screening ... Cystic fibrosis is a disease passed down through families. CF causes thick, sticky mucus to build up in ...

  8. 线粒体tRNALeu(UUR)基因nt3243A→G突变糖尿病临床特点分析%Prevalence and clinical characteristics of the mitochondriai tRNALeu(UUR) gene 3243 A to G mutation in familial diabetes mellitus in Chinese population

    Institute of Scientific and Technical Information of China (English)

    王遂军; 吴松华; 郑泰山; 王凌; 陆惠娟; 项坤三

    2009-01-01

    目的 了解线粒体tRNALeu(UUR)基因nt3243A→G突变在上海及江浙地区家族性糖尿病人群中的发生率及其临床特点.方法 应用聚合酶链反应-限制性片段长度多态结合直接测序方法对随机抽取的无亲缘关系的770个糖尿病家系的先证者进行线粒体tRNA基因nt3243A→G突变的筛查,并进一步对阳性先证者家系进行家系遗传学及临床特点分析.结果 在770个糖尿病先证者中发现13例(1.69%)nt3243A→G突变.13个先证者家系的一级亲属中共检出32例3243突变携带者,其中24例为糖尿病,8例糖耐量正常,17例伴不同程度听力减退.24例糖尿病患者多呈消瘦体型,有18例呈典型母系遗传,13例伴胰岛素抵抗,15例伴听力障碍,14例应用胰岛素治疗.结论 上海及江浙地区家族性糖尿病人群线粒体3243点突变检出率是1.69%,线粒体糖尿病患者的临床特点是:(1)多数呈母系遗传,少数可为散发;(2)多于45岁以前发病;(3)体型多偏瘦;(4)胰岛β细胞分泌功能明显降低,部分患者同时伴有胰岛素抵抗;(5)多数患者伴神经性听力障碍或神经性耳聋.%Objective To study the prevalence and clinical characteristics of the A to G mutation at nucleotide 3243 of the mitochondrial tRNALeu(UUR) gene in familial diabetes in Shanghai, Jiangsu and Zhejiang Province of China. Methods The mt3243 A to G mutation in 770 randomly selected, unrelated probands of diabetic pedigrees were screened by PCR-RFLP technique and PCR-direct sequencing. Genetic and clinical analyses were further performed in the prohands and their family members. Results Thirteen diabetic patients (13/770, 1.69%) with mt3243 A to G mutation were detected. Eleven diabetic patients and 8 normal glucose tolerance (NGT) first-degree relatives of these 13 probands were also found bearing the mutation. Seventeen patients were associated with sensory hearing loss. In the 24 patients harboring the mutation, the majority had lower body

  9. Insulin aspart in diabetic pregnancy

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R

    2008-01-01

    Pregnancy in women with diabetes is associated with an increased risk of obstetric complications and perinatal mortality. Maintenance of near-normal glycemia during pregnancy can bring the prevalence of fetal, neonatal and maternal complications closer to that of the nondiabetic population. Changes...... in insulin requirements during pregnancy necessitate short-acting insulins for postprandial control of hyperglycemia. The fast-acting insulin analogue insulin aspart has been tested in a large, randomized trial of pregnant women with Type 1 diabetes and offers benefits in control of postprandial...... and no increase in insulin antibodies was found. Thus, the use of insulin aspart in pregnancy is regarded safe....

  10. Oxidative stress in diabetic patients with retinopathy

    African Journals Online (AJOL)

    blood sugar (FBS) in diabetic patients with and without retinopathy. Materials and Methods: The .... to DNA may induce cell death or mutation that could give rise, several ..... from the peroxidative damage of the membrane lipids. Jennings et al.

  11. Neonatal haemostasis and the management of neonatal thrombosis.

    Science.gov (United States)

    Will, Andrew

    2015-05-01

    Two detailed reviews of the management of neonatal thrombosis were published in 2012; one was an up-dated version of guidance first issued in 2004 and the other was a comprehensive review. Both of these publications gave very similar advice regarding the practical aspects of the indications, dosage and management of antithrombotic therapy. The authors stated that the evidence supporting most of their recommendations for anti-thrombotic therapy in neonates remained weak and so the therapy for a neonate with a thrombosis has to be based on an individualized assessment of estimated risk versus potential benefit. The aim of this present review is to give the treating physician an outline of the unique physiology of neonatal coagulation and how this affects the monitoring, dosing and even the choice of therapeutic strategy for the management of thrombosis in the neonate.

  12. 三因素三水平正交试验用于运动疗法对妊娠期糖尿病母婴结局的观察%Observation for the effect of three factors and three levels orthogonal test used for exercise therapy intervention outcomes of gestational diabetes maternal and neonatal

    Institute of Scientific and Technical Information of China (English)

    张婵; 许冬炜; 张华; 郭爽

    2014-01-01

    目的:观察正交试验用于运动疗法干预对妊娠期糖尿病(GDM)妊娠母婴结局的影响,为制定科学的运动干预方法提供依据。方法纳入我院妇产科GDM产妇216例(GDM组),采用正交试验运动疗法干预加糖尿病健康教育,试验开始前再随机分为运动(A)组和非运动(B)组,比较各组糖尿病曲线下面积(AUC)。另选择同期于我院分娩,糖耐量正常产妇220名(NGT组)。比较两组一般实验室检查资料、BMI、羊水指数、产后出血量、新生儿阿氏评分及并发症等差异。结果通过正交试验运动疗法加糖尿病健康教育干预后,A组AUC为(519.69~650.39)mmol/(L·min),平均(585.65±30.78)mmol/(L·min),B组为(539.19~692.45)mmol/(L·min),平均(614.27±35.45)mmol/(L·min)(P=0.001)。GDM组FPG、2hPG、HbA1c及BMI较干预前均降低(P<0.05),与NGT组比较,差异均无显著意义(P>0.05)。GDM组孕妇羊水过多、早产、胎膜早破、先兆子痫、巨大儿、胎儿窘迫、产后出血发生情况与NGT组比较,差异无显著意义(P>0.05);阿氏评分<7分、剖宫产、妊高症及新生儿黄疸情况与NGT组比较,差异有显著意义(P<0.05)。结论正交试验用于运动干预加糖尿病健康教育能够改善GDM患者血糖水平,显著改善妊娠结局,并能降低围产儿发病率,对提高护理围产质量具有重要意义。%Objective To observe the effect of orthogonal test used for exercise therapy intervention outcomes of gestational diabetes(GD) maternal and neonatal .Method 216 cases maternity childbirth GD (GD group) in obstetrics and gynecology of our hospital was included in the study .Orthogonal exercise therapy intervention and diabetes health education was used .Patients were randomly divided into exercise group (A) and non-exercise group (B) be-fore the trail .Compared

  13. Aorta Structural Alterations in Term Neonates: The Role of Birth and Maternal Characteristics

    Directory of Open Access Journals (Sweden)

    Marco Matteo Ciccone

    2013-01-01

    Full Text Available Aim. To evaluate the influence of selected maternal and neonatal characteristics on aorta walls in term, appropriately grown-for-gestational age newborns. Methods. Age, parity, previous abortions, weight, height, body mass index before and after delivery, smoking, and history of hypertension, of diabetes, of cardiovascular diseases, and of dyslipidemia were all assessed in seventy mothers. They delivered 34 males and 36 females healthy term newborns who underwent ultrasound evaluation of the anteroposterior infrarenal abdominal aorta diameter (APAO, biochemical profile (glucose, insulin, total cholesterol, HDL and LDL cholesterol, triglycerides, fibrinogen, and D-dimers homeostasis model assessment [HOMAIR]index, and biometric parameters. Results. APAO was related to newborn length (r=+0.36; P=0.001, head circumference (r=+0.37; P=0.001, gestational age (r=+0.40, P=0.0005, HOMA index (r=+0.24; P=0.04, and D-dimers (r=+0.33, P=0.004. Smoke influenced APAO values (odds ratio: 1.80; confidence interval 95%: 1.05–3.30, as well as diabetes during pregnancy (r=+0.42, P=0.0002. Maternal height influenced neonatal APAO (r=+0.47, P=0.00003. Multiple regression analysis outlined neonatal D-dimers as still significantly related to neonatal APAO values. Conclusions. Many maternal and neonatal characteristics could influence aorta structures. Neonatal D-dimers are independently related to APAO.

  14. A novel mutation of the fibrillin-1 gene in a newborn with severe Marfan syndrome.

    Science.gov (United States)

    Kochilas, L; Gundogan, F; Atalay, M; Bliss, J M; Vatta, M; Pena, L S; Abuelo, D

    2008-04-01

    Marfan syndrome in the neonatal age represents a severe early and commonly lethal manifestation of Marfan syndrome, which is caused by mutations in the gene encoding fibrillin-1 (FBN1). Here, we report a newborn with severe Marfan syndrome and a novel mutation involving cysteine substitution within one of the epidermal growth factor-like domains of FBN1.

  15. Meningite neofatal: aspectos associados Neonatal meningitis: related features

    Directory of Open Access Journals (Sweden)

    Diogo C. Haussen

    2005-09-01

    Full Text Available INTRODUÇÃO: O objetivo deste estudo foi identificar e analisar fatores relacionados à meningite neonatal. MÉTODO: Em estudo de caso-controle, foram examinados neonatos com meningite no período de agosto/2002 a dezembro/2003 na Unidade de Tratamento Intensivo Neonatal (UTIN e alocados recém-nascidos hígidos como grupo controle (GC. Foram relatados dados referentes à gestação, ao parto e ao neonato. Os resultados foram considerados significativos quando p (alfaOBJECTIVE: The goal of this study was to identify and to analyze the features related to the occurrence of neonatal meningitis. METHOD: In a case-control study we examined all newborns presenting meningitis between August/2002 and December/2003 in the neonatal Intensive Care Unit. Healthy newborns were enrolled as a Control Group (CG. Data related to pregnancy, labor and the neonate itself were collected. The results with p<0,05 were considered significant. RESULTS: 42 newborns with meningitis were compared to 42 controls. The meningitis group (MG presented a lower number of medical visits during the prenatal care. The most common abnormalities detected in both groups were: drug addiction, congenital infections, preeclampsia, eclampsia, gestational diabetes mellitus and urinary tract infections. Fetal respiratory distress and the use of respiratory support were related to the occurrence of meningitis. The average weight and the APGAR scores were lower in the MG. The prevalence of premature and small for the gestational age infants was significantly higher in the MG. The neurological examination detected abnormalities in 35.7% of the meningitis cases. CONCLUSION: The association of risk factors related to pregnancy, labor and the newborn itself to the neonatal meningitis outcome in our setting is similar to the described in the literature.

  16. OXYTOCIN INDUCED NEONATAL HYPERBILIRUBINEMIA

    Directory of Open Access Journals (Sweden)

    Smita S.

    2015-05-01

    Full Text Available INTRODUCTION: Hyperbilirubinemia is one of the most common causes of health problems, observed in 60% of term and 80% of preterm infants in the first week of life . Hyperbilirubinemia leads to neurotoxicity in severe condition. Some studies suggests that liberal use of oxytocin for inducing labour is one of the factor which lead to neonatal hyperbilirubinemia. OBJECTIVE: To compare the effect of oxytocin and neonatal bilirubin levels with spontaneous vaginal delivery . MATERIALS AND METHOD S : 100 full term parturients were selected for this study. The subjects were divided into two groups. 50 healthy babies of women who had oxytocin induced labour and 50 healthy babies of women with normal vaginal delivery following spontaneous onset of labour formed the control group. Neon atal serum bilirubin was measured on day 1, 3 and 5 after delivery. Bilirubin was measured by spectrophotometry. Data was analysed in ms excel sheet using spss 19.0v. Statistical analysis was done by using unpaired‘t’ test. RESULTS: There was significant i ncrease in bilirubin level in oxytocin induced group compared to control group on day 1 and 3. There was insignificant increase in bilirubin level in oxytocin induced group on day 5. However the level of serum bilirubin is within normal limits as bilirubin level normally rises on till 4 th day and decreases thereafter. CONCLUSION: Neonatal hyperbilirubinemia may be due to oxytocin administration by continues IV infusion which results in erythrocyte swell and rupture. Increase in bilirubin level in oxytocin i nduced group is within physiological limits

  17. Diabetic parturient - Anaesthetic implications

    Directory of Open Access Journals (Sweden)

    Nibedita Pani

    2010-01-01

    Full Text Available Pregnancy induces progressive changes in maternal carbohydrate metabolism. As pregnancy advances insulin resistance and diabetogenic stress due to placental hormones necessitate compensatory increase in insulin secretion. When this compensation is inadequate gestational diabetes develops. ′Gestational diabetes mellitus′ (GDM is defined as carbohydrate intolerance with onset or recognition during pregnancy. Women diagnosed to have GDM are at increased risk of future diabetes predominantly type 2 DM as are their children. Thus GDM offers an important opportunity for the development, testing and implementation of clinical strategies for diabetes prevention. Timely action taken now in screening all pregnant women for glucose intolerance, achieving euglycaemia in them and ensuring adequate nutrition may prevent in all probability, the vicious cycle of transmitting glucose intolerance from one generation to another. Given that diabetic mothers have proportionately larger babies it is likely that vaginal delivery will be more difficult than in the normal population, with a higher rate of instrumentally assisted delivery, episiotomy and conversion to urgent caesarean section. So an indwelling epidural catheter is a better choice for labour analgesia as well to use, should a caesarean delivery become necessary. Diabetes in pregnancy has potential serious adverse effects for both the mother and the neonate. Standardized multidisciplinary care including anaesthetists should be carried out obsessively throughout pregnancy. Diabetes is the most common endocrine disorder of pregnancy. In pregnancy, it has considerable cost and care demands and is associated with increased risks to the health of the mother and the outcome of the pregnancy. However, with careful and appropriate screening, multidisciplinary management and a motivated patient these risks can be minimized.

  18. Cantu syndrome is caused by mutations in ABCC9

    NARCIS (Netherlands)

    Bon, B.W. van; Gilissen, C.; Grange, D.K.; Hennekam, R.C.; Kayserili, H.; Engels, H.; Reutter, H.; Ostergaard, J.R.; Morava, E.; Tsiakas, K.; Isidor, B.; Merrer, M. le; Eser, M.; Wieskamp, N.; Vries, P. de; Steehouwer, M.; Veltman, J.A.; Robertson, S.P.; Brunner, H.G.; Vries, B.B. de; Hoischen, A.

    2012-01-01

    Cantu syndrome is a rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. Using an exome-sequencing approach applied to one proband-parent trio and three unrelated single cases, we identified heterozygous mutations in ABCC9

  19. The conundrum of neonatal coagulopathy.

    Science.gov (United States)

    Revel-Vilk, Shoshana

    2012-01-01

    The maturation and postnatal development of the human coagulation system was first studied and described more than 20 years ago. These older studies, supported by more recent data, confirm the significant and important differences in the physiology of coagulation and fibrinolysis in neonates and young children compared with older children and adults. Subsequently, significant differences were also described in the physiology of primary hemostasis and in global in vitro tests for hemostasis. These differences, which mostly reflect the immaturity of the neonatal hemostasis system, are functionally balanced. Healthy neonates show no signs of easy bruising or other bleeding diathesis and no increased tendency to thrombosis for any given stimulus compared with adults. Systemic diseases may affect hemostasis, predisposing ill neonates to increased hemorrhagic or thrombotic complications. The immaturity of the hemostasis system in preterm and very-low-birth-weight neonates may contribute to a higher risk for intraventricular hemorrhage. Therapies targeting the hemostasis system can be effective for preventing and treating these events. The concept of "neonatal coagulopathy" has an important impact on both the diagnosis and management of hemorrhagic or thrombotic events in neonates. For diagnosis of hemostasis disorders, diagnostic laboratories processing pediatric samples should use age-, analyzer-, and reagent-appropriate reference ranges. Age-specific guidelines should be followed for the management of neonates with hemostatic disorders.

  20. Bacterial sepsis in the neonate.

    Science.gov (United States)

    Rubarth, Lori Baas; Christensen, Carla M; Riley, Cheryl

    2017-09-21

    Neonatal bacterial infections leading to sepsis occur frequently in the first few days or weeks of life. NPs must be able to recognize the early signs of sepsis and understand the need for rapid evaluation and treatment. This article discusses antibiotic treatments for various types and locations of bacterial infections and sepsis in the neonate.

  1. Neonatal Candida arthritis

    Directory of Open Access Journals (Sweden)

    Saurabh Sharma

    2014-01-01

    Full Text Available Fungal arthritis is an uncommon yet serious disorder in the newborn. Delay in diagnosis and management can lead to significant morbidity. We report our experience with management of two such cases. Two preterm neonates with multifocal arthritis caused by Candida were studied. Diagnosis was made by clinical examination, laboratory investigations, radiological investigations and culture. Both were treated by aspiration, arthrotomy and antifungal therapy. One patient recovered fully from the infection while the other had growth disturbances resulting in limb length inequality at recent followup. Prompt and expeditious evacuation of pus from joints and antifungal therapy is imperative for treatment. Associated osteomyelitis leads to further difficulty in treatment.

  2. Hemolysis in Preterm Neonates.

    Science.gov (United States)

    Christensen, Robert D; Yaish, Hassan M

    2016-06-01

    Hemolysis can be an important cause of hyperbilirubinemia in premature and term neonates. It can result from genetic abnormalities intrinsic to or factors exogenous to normal to red blood cells (RBCs). Hemolysis can lead to a relatively rapid increase in total serum/plasma bilirubin, hyperbilirubinemia that is somewhat slow to fall with phototherapy, or hyperbilirubinemia that is likely to rebound after phototherapy. Laboratory methods for diagnosing hemolysis are more difficult to apply, or less conclusive, in preterm infants. Transfusion of donor RBCs can present a bilirubin load that must be metabolized. Genetic causes can be identified by next-generation sequencing panels.

  3. Interpretation of neonatal chest radiography

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hye Kyung [Dept. of Radiology, Kangwon National University Hospital, Chuncheon (Korea, Republic of)

    2016-05-15

    Plain radiographs for infants in the neonatal intensive care unit are obtained using the portable X-ray equipment in order to evaluate the neonatal lungs and also to check the position of the tubes and catheters used for monitoring critically-ill neonates. Neonatal respiratory distress is caused by a variety of medical or surgical disease conditions. Clinical information about the gestational week, respiratory symptoms, and any events during delivery is essential for interpretation of the neonatal chest radiographs. Awareness of common chest abnormality in the prematurely born or term babies is also very important for chest evaluation in the newborn. Furthermore, knowledge about complications such as air leaks and bronchopulmonary dysplasia following treatment are required to accurately inform the clinicians. The purpose of this article was to briefly review radiographic findings of chest diseases in newborns that are relatively common in daily practice.

  4. Functional and immunohistochemical evaluation of porcine neonatal islet-like cell clusters

    DEFF Research Database (Denmark)

    Nielsen, T B; Yderstraede, K B; Schrøder, H D

    2003-01-01

    Porcine neonatal islet-like cell clusters (NICCs) may be an attractive source of insulin-producing tissue for xenotransplantation in type I diabetic patients. We examined the functional and immunohistochemical outcome of the islet grafts in vitro during long-term culture and in vivo after transpl...

  5. Timing of elective cesarean section and neonatal morbidity: A randomized controlled trial

    DEFF Research Database (Denmark)

    Glavind, Julie; Kindberg, Sara Fevre; Uldbjerg, Niels

    2012-01-01

    . Diabetics and women with an estimated high risk of having ECS before 39 weeks and 5 days of gestation were excluded. The primary outcome was admission to the Neonatal Intensive Care Unit within 48 hours of birth. Results From March 2009 to June 2011 1274 women from seven Danish hospitals were enrolled...

  6. Metformin attenuates hyperoxia-induced lung injury in neonatal rats by reducing the inflammatory response

    NARCIS (Netherlands)

    Chen, Xueyu; Walther, Frans J; Sengers, Rozemarijn M A; Laghmani, El Houari; Salam, Asma; Folkerts, Gert; Pera, Tonio; Wagenaar, Gerry T M

    2015-01-01

    Because therapeutic options are lacking for bronchopulmonary dysplasia (BPD), there is an urgent medical need to discover novel targets/drugs to treat this neonatal chronic lung disease. Metformin, a drug commonly used to lower blood glucose in type 2 diabetes patients, may be a novel therapeutic op

  7. Diabetes mellitus

    OpenAIRE

    Nessim Dayan, Edgard; Fundación Valle de Lili

    1996-01-01

    ¿Qué es la diabetes?/¿Cuantos tipos o formas de diabetes existen?/¿Cuáles son los síntomas de la diabetes?/¿cuál es la causa de la diabetes?/¿Quién tiene mayor riesgo de desarrollar diabetes?/¿Cómo se diagnostica la diabetes?/¿Cuál es el tratamiento de la diabetes?/¿Cuándo y cómo se controlan los niveles de glicemia?/¿Cuáles son las complicaciones de la diabetes?/Recomendaciones actuales y futuro de la diabetes.

  8. Diabetic Nephropathy without Diabetes

    Directory of Open Access Journals (Sweden)

    Katia López-Revuelta

    2015-07-01

    Full Text Available Diabetic nephropathy without diabetes (DNND, previously known as idiopathic nodular glomerulosclerosis, is an uncommon entity and thus rarely suspected; diagnosis is histological once diabetes is discarded. In this study we describe two new cases of DNND and review the literature. We analyzed all the individualized data of previous publications except one series of attached data. DNND appears to be favored by recognized cardiovascular risk factors. However, in contrast with diabetes, apparently no factor alone has been demonstrated to be sufficient to develop DNND. Other factors not considered as genetic and environmental factors could play a role or interact. The most plausible hypothesis for the occurrence of DNND would be a special form of atherosclerotic or metabolic glomerulopathy than can occur with or without diabetes. The clinical spectrum of cardiovascular risk factors and histological findings support this theory, with hypertension as one of the characteristic clinical features.

  9. Screening for Mutations of MODY 1-5 Genes in Chinese Families with Early-onset Type 2 Diabetes%中国早发2型糖尿病家系MODY 1-5基因测定

    Institute of Scientific and Technical Information of China (English)

    严晋华; 沈云峰; 余秋琼; 梁华; 蔡梦茵; 翁建平

    2009-01-01

    [Objective] The aim of our study was to seek the mutations in MODY1~5 genes in Chinese population by direct sequencing in probands from families with early-onset type 2 diabetes.[Methods] Variants screening in MODY 1-5 genes were performed by PCR and direct sequencing in 19 probands from early-onset type 2 diabetes families.[Results] We found no mutation but many polymorphisms.There were 6,5,15,1,and 1 variants in MODY 1-5 genes respectively.[Conclusion] Our negative results in MODY genes suggest the genetic heterogeneity of different populations.Mutations in MODY 1-5 genes might not be the cause of diabetes in those 19 families.%[目的] 通过对早发2型糖尿病家系先证者进行直接测序,寻找中国人群中可能存在的青少年的成人发病型糖尿病(MODY) 1-5基因突变.[方法] 对19个早发2型糖尿病家系的先证者进行MODY 1-5基因扩增和DNA直接测序.[结果] 19个先证者未发现MODY基因突变,但发现MODY 1-5基因分别存在6、5、15、1、1种多态性.[结论] MODY相关基因突变具有种族异质性,MODY 1-5基因突变不是该19个早发糖尿病家系的致病因素.

  10. Screening for gestational diabetes mellitus : US preventive services task force recommendation statement

    NARCIS (Netherlands)

    Calonge, Ned; Petitti, Diana B.; DeWitt, Thomas G.; Gordis, Leon; Gregory, Kimberly D.; Harris, Russell; Isham, George; LeFevre, Michael L.; Loveland-Cherry, Carol; Marion, Lucy N.; Moyer, Virginia A.; Ockene, Judith K.; Sawaya, George F.; Siu, Albert L.; Teutsch, Steven M.; Yawn, Barbara P.

    2008-01-01

    Description: Update of 2003 U. S. Preventive Services Task Force (USPSTF) recommendation about screening for gestational diabetes. Methods: The USPSTF weighed the evidence on maternal and neonatal benefits (reduction in preeclampsia, mortality, brachial plexus injury, clavicular fractures, admission

  11. Neonatal gastrointestinal imaging

    Energy Technology Data Exchange (ETDEWEB)

    Rao, Padma [Department of Radiology, Royal Children' s Hospital and University of Melbourne, Flemington Road, Parkville, Melbourne, Vic. 3052 (Australia)]. E-mail: padma.rao@rch.org.au

    2006-11-15

    Radiological imaging is an important part of the evaluation and management of neonates with suspected anomalies of the gastrointestinal tract. Clinical presentation is often non-specific, commonly with abdominal distension and vomiting for which the underlying cause may or may not be clinically apparent. In a proportion of patients, the clinical assessment alone may suffice in providing the diagnosis and no further imaging is necessary. The reader must have an understanding of the normal radiographic appearances of the gastrointestinal tract in neonates and appreciate normal variants and differences to adults. In certain cases, the abdominal radiograph alone is diagnostic. In others, sonography and contrast studies are useful adjunct investigations and the indications for CT and MRI are few, but specific. Appropriate radiological investigation will help to establish the diagnosis and guide surgical intervention whilst also avoiding unnecessary radiation. Some of the conditions require transfer to specialist paediatric institutions for care. Thus, in some circumstances it is appropriate for imaging to be delayed and performed at the specialist centre with early referral often essential for the continued well being of the child.

  12. Neonatal status of twins

    Directory of Open Access Journals (Sweden)

    Božinović Dragica

    2012-01-01

    Full Text Available Multiple pregnancy is a pregnancy where more than one fetus develops simultaneously in the womb, as a result of the ovulation and fertilization of more than one egg. It is relatively rare in humans and represents the rest of the phylogenetic stages. The most common are twins and they indicate the development of two fetuses in the womb. The frequency of twin pregnancies is about 1%. Multiple pregnancies belong to a group of high-risk pregnancies because of the many complications that occur during the pregnancy: higher number of premature deliveries, bleeding, early neonatal complications and higher perinatal morbidity and mortality. Such pregnancies and infants require greater supervision and monitoring. The aim of this study was to determine the percentage of baby twins born at the maternity ward of the General Hospital in Prokuplje and their morbidity and mortality. Data on the total number of deliveries, number of twins, parity and maternal age, gestational age, body weight of twins, method of delivery, Apgar score and perinatal mortality were collected and statistically analyzed by means of retrospective analysis of operative birth and neonatal protocol for 6 years (2005 of 2010. Out of 4527 mothers who gave birth 43 were pairs of twins, or 0.95% of women gave birth to twins. These babies are more likely born by Caesarean section, but delivered with slightly lower birth weight.

  13. A complex V ATP5A1 defect causes fatal neonatal mitochondrial encephalopathy

    NARCIS (Netherlands)

    Jonckheere, A.I.; Renkema, G.H.; Bras, M.; Heuvel, L.P.W.J. van den; Hoischen, A.; Gilissen, C.F.H.A.; Nabuurs, S.B.; Huynen, M.A.; Vries, M.C. de; Smeitink, J.A.M.; Rodenburg, R.J.T.

    2013-01-01

    Whole exome sequencing is a powerful tool to detect novel pathogenic mutations in patients with suspected mitochondrial disease. However, the interpretation of novel genetic variants is not always straightforward. Here, we present two siblings with a severe neonatal encephalopathy caused by complex

  14. The Placental Microbiome Varies in Association with Low Birth Weight in Full-Term Neonates

    Directory of Open Access Journals (Sweden)

    Jia Zheng

    2015-08-01

    Full Text Available Substantial evidence indicated that low birth weight was an independent risk factor for obesity, impaired glucose regulation, and diabetes later in life. However, investigations into the association between low birth weight and placental microbiome in full-term neonates are limited. Placentas were collected from low birth weight (LBW and normal birth weight (NBW full-term neonates (gestational age 37 w0d–41 w6d consecutively born at Peking Union Medical College Hospital. The anthropometric measurements were measured and 16S ribosomal DNAamplicon high-throughput sequencing were utilized to define bacteria within placenta tissues. It showed that birth weight, ponderal index, head circumference, and placenta weight were significantly lower in LBW than NBW neonates (p < 0.05. The operational taxonomic units (OTUs (p < 0.05 and the estimators of community richness (Chao indexes (p < 0.05 showed a significantly lower diversity in LBW than NBW neonates. There were significant variations in the composition of placenta microbiota between the LBW and NBW neonates at the phylum and genus level. Furthermore, it indicated that Lactobacillus percentage was positively associated with birth weight (r = 0.541, p = 0.025. In conclusion, our present study for the first time detected the relationship between birth weight and placental microbiome profile in full-term neonates. It is novel in showing that the placental microbiome varies in association with low birth weight in full-term neonates.

  15. 一中国人家系常染色体显性遗传垂体性尿崩症基因突变研究%Mutation of autosomal dominant neurohypophyseal diabetes insipidus in a Chinese pedigree

    Institute of Scientific and Technical Information of China (English)

    陈育才; 谢文煌; 王柠; 慕容慎行; 黄妙辉; 黄梅芳

    2001-01-01

    Objective To elucidate the molecular mechanism of autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) in Chinese. Methods A Chinese family with ADNDI was studied. Polymerase chain reaction-single strand conformation polymorphisms (PCR-SSCP) of exon 1 and exon 2 of arginine vasopressin neurophysin Ⅱ (AVP-NPII) gene were performed in 4 patients and 4 normal phenotypic members of the pedigree and 1 patient from other family. Direct DNA sequencing of PCR-amplified geomic DNA in exon 2 are carried out. Results In exon 1, the affected patients and unaffected people in same kindred and a nonfamilial insipidus from other family had the same strand in SSCP analysis. But there were differences in SSCP analysis from exon 2 as follows: besides having the same strand as healthy man in same kindred or a nonfamilial affected patient, SSCP analysis showed that affected patients from ADNDI had two new different strands. The results were confirmed by direct DNA sequencing of PCR-amplified geomic DNA. A 3-base pair deletion (GAG) out of two consecutive GAG sequence (nucleotides 1826-1831) was identified in affected individual with ADNDI. This mutation should yield an abnormal AVP precursor lacking Glu47 in its neurophysin-Ⅱ moeity. Since Glu47 is essential for NP molecules to form a salt bridge with AVP, the function of NP as a carrier proetin for AVP would be impaired which leads to acceleration proteolytic degradation. Conclusion The nucleotides deletion in the coding region for neurophysin Ⅱ gene appears to be one of the causes of autosomal dominant neurohypophyseal diabetes insipidus in Chinese.%目的 探讨中国人的常染色体显性遗传垂体性尿崩症(ADNDI)的分子发病机制。方法 对一个家系中4例ADNDI患者、4例未发病者及1例来自其他家庭的患者的精氨酸加压素-运载蛋白Ⅱ(AVP-NPⅡ)基因外显子1和2进行聚合酶链反应-单链构像多态性(PCR-SSCP)分析及基因测序研究。结果 SSCP分

  16. Long-term breast-feeding in women with type 1 diabetes

    DEFF Research Database (Denmark)

    Stage, E; Nørgård, Hanne; Damm, Peter

    2006-01-01

    Breast-feeding may be more difficult in women with diabetes because of neonatal morbidity and fluctuating maternal blood glucose values. The frequency of long-term breast-feeding and the possible predictors for successful breast-feeding were investigated.......Breast-feeding may be more difficult in women with diabetes because of neonatal morbidity and fluctuating maternal blood glucose values. The frequency of long-term breast-feeding and the possible predictors for successful breast-feeding were investigated....

  17. Long-term breast-feeding in women with type 1 diabetes

    DEFF Research Database (Denmark)

    Stage, E; Nørgård, Hanne; Damm, Peter

    2006-01-01

    Breast-feeding may be more difficult in women with diabetes because of neonatal morbidity and fluctuating maternal blood glucose values. The frequency of long-term breast-feeding and the possible predictors for successful breast-feeding were investigated.......Breast-feeding may be more difficult in women with diabetes because of neonatal morbidity and fluctuating maternal blood glucose values. The frequency of long-term breast-feeding and the possible predictors for successful breast-feeding were investigated....

  18. Diabetes Medicines

    Science.gov (United States)

    Diabetes means your blood glucose, or blood sugar, levels are too high. If you can't control your diabetes with wise food choices and physical activity, you may need diabetes medicines. The kind of medicine you take depends ...

  19. Glucose control in pregnant women with type 1 diabetes mellitus: Studies using a continuous glucose monitoring system

    NARCIS (Netherlands)

    Kerssen, Anneloes

    2005-01-01

    Pregnancy in women with type 1 diabetes mellitus is associated with neonatal morbidity. It is commonly agreed that the morbidity decreases when diabetic control is tightened. The most common methods for the determination of diabetic control are the self-monitoring of blood glucose levels (SMBG) and

  20. Pyridoxine responsive epilepsy caused by a novel homozygous PNPO mutation

    Directory of Open Access Journals (Sweden)

    B. Jaeger

    2016-03-01

    Full Text Available We report a patient with anti-epileptic treatment refractory neonatal seizures responsive to pyridoxine. Biochemical analysis revealed normal markers for antiquitin deficiency and also mutation analysis of the ALDH7A1 (Antiquitin gene was negative. Mutation analysis of the PNPO gene revealed a novel, homozygous, presumed pathogenic mutation (c.481C>T; p.(Arg161Cys. Measurements of B6 vitamers in a CSF sample after pyridoxine administration revealed elevated pyridoxamine as the only metabolic marker for PNPO deficiency. With pyridoxine monotherapy the patient is seizure free and neurodevelopmental outcome at the age of 14 months is normal.

  1. EVALUATION OF NEONATAL CARDIAC MURMURS

    Directory of Open Access Journals (Sweden)

    Somaiah

    2014-09-01

    Full Text Available Cardiovascular malformations are the most common cause of congenital malformations, the diagnosis of which requires a close observation in the neonatal period. Early recognition of CHD is important in the neonatal period, as many of them may be fatal if undiagnosed and may require immediate intervention. The objectives of this study are to study the epidemiology of neonatal cardiac murmurs, to identify clinical characteristics which differentiate pathological murmur from functional murmurs and to assess the reliability of clinical evaluation in diagnosing CHD. Method of study included all neonates admitted to the NICU, postnatal ward, attending pediatric OPD or neonatal follow up clinic and were detected to have cardiac murmurs. It was a cross sectional study over a period of 16months. A clinical diagnosis was made based on history and clinical examination. Then Chest X-ray and ECG, Echocardiography was done in all neonates for confirmation of the diagnosis. These neonates were again examined daily till they were in hospital and during the follow-up visit at 6 weeks. The results of 70 neonates in this study conducted over a period of 24 months included the incidence of cardiac murmurs among intramural neonates which was 13.5 for 1000 live births. Most frequent symptom was fast breathing in 10(14.3% cases. VSD was the most common diagnosis clinically in 23 (33% babies. The most frequent Echo diagnosis was acyanotic complex congenital heart disease in 25(36% cases followed by 12(17% cases each of VSD and ASD respectively. Overall in our study 77.1% (54cases of the murmurs were diagnosed correctly and confirmed by Echocardiography The study concluded that it is possible to make clinical diagnosis in many cases of congenital heart diseases, the functional murmurs could be differentiated from those arising from structural heart disease and evaluation of the infants based only on murmurs, few congenital heart diseases can be missed.

  2. Oxidative stress in the neonate.

    Science.gov (United States)

    Robles, R; Palomino, N; Robles, A

    2001-11-01

    The aim of this study is to determine the oxidative state of term and preterm neonates at the moment of birth and during the first days of life, and the influence of exposure to oxygen on the premature neonates.A total of 20 neonates were selected. Group A: 10 healthy full-term neonates, and Group B: 10 preterm neonates with no other pathology associated, requiring oxygen therapy. Venous samples were taken in cord at 3 and 72 h in Group A, and in cord at 3, 24 and 72 h and 7 days in Group B.Hydroperoxides, Q10 coenzyme (Co Q10) and alpha-tocopherol were measured within the erythrocyte membrane. Levels of hydroperoxides present in erythrocyte membrane were higher than normal both in Group A and in Group B at birth. This increase was greater in the group of premature neonates. Levels of alpha-tocopherol at birth increase significantly at 72 h in term neonates. Among the premature newborns, alpha-tocopherol levels are two to three times lower at birth and do not rise to higher levels as in the term neonate group. Fall in levels of Co Q10 in erythrocyte membranes is observed, and perhaps is due to the role of Co Q10 in maintaining the pool of reduced tocopherol. At birth, the neonate presents an increase of markers of oxidative stress and a decrease of their antioxidant defenses. This difference is greater as gestational age decreases. The application of oxygen therapy resulted in these levels which remain low throughout the study period.

  3. Aquaporin 2 mutations in nephrogenic diabetes insipidus.

    NARCIS (Netherlands)

    Loonen, A.J.M.; Knoers, N.V.A.M.; Os, C.H. van; Deen, P.M.T.

    2008-01-01

    Water reabsorption in the renal collecting duct is regulated by the antidiuretic hormone vasopressin (AVP). When the vasopressin V2 receptor, present on the basolateral site of the renal principal cell, becomes activated by AVP, aquaporin-2 (AQP2) water channels will be inserted in the apical

  4. Mutation analysis of 28 gaucher disease patients: The Australasian experience

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, B.D.; Nelson, P.V.; Robertson, E.F.; Morris, C.P. [Women`s and Children`s Hospital, North Adelaide, South Australia (Australia)

    1994-01-15

    Gaucher disease is the most common lysomal storage disease. It is an autosomal recessive disorder that results from a deficiency of {beta}-glucocerrebrosidase. Three clinical phenotypes have been described: non-neuronopathic, acute neuronopathic, and subacuteneuronopathic. Genomic DNA from 28 Australasian patients of diverse ethnic origin with Gaucher disease was screened for 3 common mutations (1226G, 1448C and 84GG) using the amplification refractory mutation system (ARMS), and one uncommon mutation (1504T) by restriction enzyme digestion. Thirty-eight of the 56 independent alleles in these patients were characterized, with 1448C present in 42% and 1226G in 28% of the alleles. The 1226G mutation was associated only with the nonneuronopathic phenotype and 7 of the 15 patients who carried the 1448C mutation developed neuronopathic disease. Three infants who died in the neonatal period following a rapidly progressive neurodegenerative course carried no identifiable mutations. The 84GG mutation was carried by 2 Jewish patients and 1504T was present in one patient. It is now possible to rapidly identify the common Gaucher mutations using ARMS and restriction enzyme digestion, and our findings confirm the heterogeneity of mutations in Gaucher disease. It is also possible to predict in part the phenotypic outcome when screening patients for these mutations. The authors consider mutation analysis to be of most use in prenatal diagnosis and for carrier detection within affected families. 27 refs., 2 figs., 2 tabs.

  5. The Relationship between Neonatal Jaundice and Maternal and Neonatal Factors

    Directory of Open Access Journals (Sweden)

    Ehsan Garosi

    2016-03-01

    Conclusion: Since factors such as mode of delivery, oxytocin induction, and neonate's gender could contribute to jaundice, continuous assessment of newborns after birth could facilitate early diagnosis, promote disease management, and reduce the subsequent complications.

  6. Neonatal sensitization to latex.

    Science.gov (United States)

    Worth, J

    2000-05-01

    Babies born in delivery rooms of hospitals are exposed to latex through skin and mucous membrane contact with prepowdered latex gloves worn by midwives and doctors, and through the inhalation of latex-bound starch powder in the air of the delivery room. This paper examines the hypothesis that they are at risk for latex sensitization, and that part of the sharp increase of childhood asthma, eczema and anaphylaxis in the past 30-40 years may be linked. These possibilities seem hitherto unsuspected. In over 700 papers on latex allergy no mention of neonatal exposure to latex has been found. Even obstetric papers discussing the risks for an atopic mother (atopy - a tendency to develop allergies) do not seem to anticipate any risk for the baby, who might also be atopic. Latex allergy is primarily regarded as an occupational hazard. This paper suggests that it is a hazard for every baby handled by latex gloves at birth. Copyright 2000 Harcourt Publishers Ltd.

  7. Juvenile Myelomonocytic Leukemia in a Premature Neonate Mimicking Neonatal Sepsis

    Directory of Open Access Journals (Sweden)

    Ming-Luen Lee

    2016-04-01

    Full Text Available Juvenile myelomonocytic leukemia (JMML is a rare hematologic malignancy in children. Its presentations include anemia, thrombocytopenia, monocytosis, skin rash, marked hepatomegaly, and/or splenomegaly. Fever and respiratory involvement are common. Here, we report a case of a premature neonate with initial symptoms of respiratory distress. She gradually developed clinical manifestations of JMML that mimicked neonatal sepsis. Three weeks after birth, JMML was diagnosed. This is the first reported case of JMML presenting in a premature infant in Taiwan.

  8. Neonatal lupus syndromes.

    Science.gov (United States)

    Buyon, J P; Rupel, A; Clancy, R M

    2004-01-01

    The neonatal lupus syndromes (NLS), while quite rare, carry significant mortality and morbidity in cases of cardiac manifestations. Although anti-SSA/Ro-SSB/La antibodies are detected in > 85% of mothers whose fetuses are identified with congenital heart block (CHB) in a structurally normal heart, when clinicians applied this testing to their pregnant patients, the risk for a woman with the candidate antibodies to have a child with CHB was at or below 1 in 50. While the precise pathogenic mechanism of antibody-mediated injury remains unknown, it is clear that the antibodies alone are insufficient to cause disease and fetal factors are likely contributory. In vivo and in vitro evidence supports a pathologic cascade involving apoptosis of cardiocytes, surface translocation of Ro and La antigens, binding of maternal autoantibodies, secretion of profibrosing factors (e.g., TGFbeta) from the scavenging macrophages and modulation of cardiac fibroblasts to a myofibroflast scarring phenotype. The spectrum of cardiac abnormalities continues to expand, with varying degrees of block identified in utero and reports of late onset cardiomyopathy (some of which display endocardial fibroelastosis). Moreover, there is now clear documentation that incomplete blocks (including those improving in utero with dexamethasone) can progress postnatally, despite the clearance of the maternal antibodies from the neonatal circulation. Better echocardiographic measurements which identify first degree block in utero may be the optimal means of approaching pregnant women at risk. Prophylactic therapies, including treatment with intravenous immunoglobulin, await larger trials. In order to achieve advances at both the bench and bedside, national research registries established in the US and Canada are critical.

  9. A case of neonatal arterial thrombosis mimicking interrupted aortic arch.

    Science.gov (United States)

    Gürsu, Hazım Alper; Varan, Birgül; Oktay, Ayla; Özkan, Murat

    2015-06-01

    Neonatal arterial thrombosis is a very rare entity with clinical findings resembling coarctation of aorta or interrupted aortic arch. A two day-old male newborn was admitted to a different hospital with difficulty in sucking and sleepiness. On echocardiographic examination, a diagnosis of interrupted aortic arch was made and he was treated with prostoglandin E2. When the patient presented to our center, physical examination revealed that his feet were bilaterally cold. The pulses were not palpable and there were ecchymotic regions in the lower extremities. Echocardiography ruled out interrupted aortic arch. Computerized tomographic angiography revealed a large thrombosis and total occlusion of the abdominal aorta. Since there was no response to treatment with tissue plasminogen activator, we performed thrombectomy. Homozygous Factor V Leiden and Methylenetetrahydrofolate reductase mutations were found in this patient. Neonatal aortic thrombosis which is observed very rarely and fatal should be considered in the differential diagnosis of coarctation of aorta and interrupted aortic arch.

  10. Oral mexiletine for lidocaine-responsive neonatal epilepsy.

    Science.gov (United States)

    Nakazawa, Mika; Okumura, Akihisa; Niijima, Shinichi; Yamashita, Shintaro; Shimono, Kuriko; Hirose, Shinichi; Shimizu, Toshiaki

    2013-08-01

    We report a patient with lidocaine-responsive neonatal epilepsy treated successfully with oral mexiletine. The patient was a male neonate who had seizures since 2days of age. While his seizures were refractory to phenobarbital, lamotrigine, vitamin B6, and midazolam, they were controlled by continuous lidocaine infusion. Oral mexiletine at serum levels of 0.2-0.4μg/ml was used successfully for long-term treatment of his seizures. No delay in psychomotor development was observed at the last follow-up at 20months of age. No mutation was identified in any of four genes: SCN1A, SCN1B, KCNQ2, and KCNQ3. Our patient demonstrates that oral mexiletine can be useful for long-term treatment of patients with lidocaine-responsive epilepsy. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  11. Molecular genetic analysis of Type II diabetes associated m.3243A ...

    African Journals Online (AJOL)

    Saidul Abrar

    This study was carried out in 6 suspected diabetic members of a Pakistani family. ... The Egyptian Journal of Medical Human Genetics 18 (2017) 305–308. Contents lists .... mutations in diabetes mellitus patients in Chinese Han family.

  12. 妊娠期糖尿病母亲新生儿T细胞亚群及NK细胞活性的变化及其与血糖相关的研究%Changes of CD3+ , CD4+ and CD8+ T cells and natural killer cells in neonates born to gestational diabetes mellitus mothers and their relationship with blood glucose

    Institute of Scientific and Technical Information of China (English)

    王合丽; 孙学梅; 孙正芸; 王娜; 林霞

    2011-01-01

    目的 探讨妊娠期糖尿病母亲新生儿T细胞亚群及NK细胞活性的变化及其与患儿出生后24 h内微量血糖的关系.方法 选择妊娠期糖尿病母亲足月新生儿33例(观察组)及健康足月新生儿30例(对照组),应用流式细胞术检测出生后24h内静脉血CD3+、CD4+、CD8+T细胞及CD16+CD56+NK细胞;采用血糖检测仪检测新生儿生后24 h内的微量血糖,并研究观察组血糖与CD3+、CD4+、CD8+5T细胞、CD4+/CD8+、CD16+CD56+NK细胞有无相关性.结果 观察组新生儿的CD3+,CD4+T细胞计数,CD4+/CD8+比值、CD16+CD56+NK细胞活性均低于对照组新生儿(P<0.01),微量血糖亦低于对照组(P<0.05),观察组低血糖发生率21.21%,对照组无低血糖发生,两组低血糖发生率差异有统计学意义(P=0.023).CD3+、CD4+T细胞计数,CD16+CD56+NK细胞活性与微量血糖呈正相关性(P均<0.05).结论 妊娠期糖尿病可导致新生儿CD3+、CD4+T细胞计数,CD4+/CD8+比值,CD16+CD56+NK细胞活性下降,导致其免疫功能下降,应加强其围产期护理,预防新生儿期感染的发生.%Objective To investigate changes of CD3 +, CD4+ and CD8 + T cells and natural killer(NK) cells in neonates bom to gestational diabetes mellitus(GDM) mothers and their relationship with blood glucose. Methods 33 fullterm neonates bom to GDM mothers were enrolled as the experimental group and 30 healthy full-term neonates were enrolled as the control group. Numbers of CD3 +, CD4 + and CD8 + T cells and activity of NK cells were measured by flow cytometry within 24 h after birth. Blood glucose was detected by a trace glucose meter. Results Compared with the control group, numbers of CD3 + and CD4 + T cells, activity of NK cells and the ratio of CD4+/CD8+ were lower in the experimental group ( P <0.01 ). The level of blood glucose in the experimental group was lower ( P < 0.05 ).The incidence of hypoglycemia in the experimental group was 21.21%, which was higher than that in the

  13. GDM孕妇孕前体质量指数及孕期体质量指数增加对分娩方式和母婴结局的影响%Influence of pre-pregnant and pregnant body mass index of women with gestational diabetes mellitus on delivery methods and maternal and neonatal outcomes

    Institute of Scientific and Technical Information of China (English)

    于彩娥

    2016-01-01

    Objective To investigate Influence of pre-pregnant and pregnant body mass index (BMI) of women with gestational diabetes mellitus (GDM) on delivery methods and maternal and neonatal outcomes.Methods 264 women with GDM were selected and were divided into a low BMI group (BMI<18.5 kg/m2), a normal BMI group (18.5 kg/m2 ≤ BMI< 25 kg/m2), and an obesity group (BMI ≥ 25 kg/m2) according to the BMI before pregnancy and into an insufficient weight gain group, a normal weight gain group, and an excessive weight gain group according to pregnancy weight gain standard of IOM.The incidences of cesarean section, fetal distress, neonatal asphyxia, postpartum infection, and fetal macrosomia were compared between each two group.Results The cesarean section rate of the low BMI group were significantly higher than that of the normal BMI group but lower than that of the obesity group and the incidences of fetal distress, neonatal asphyxia, and puerperal infection of the low BMI group were significantly lower than those of the obesity group (P < 0.05).The incidences of cesarean section, fetal distress, fetal macrosomia, and neonatal asphyxia were significantly lower in the normal BMI group than in the obesity group (P < 0.05) and were significantly higher in the insufficient weight gain group than in the normal weight gain group and the excessive weight gain group (P < 0.05).Conclusions Perinatal health care, measuring Pre-pregnant height and weight and calculating BMI, screening obesity women before pregnancy, managing women with GDM as high risk pregnancy, taking intervention measures to control BMI less than 25 kg/m2 before pregnancy, reasonably controlling weight gain during pregnancy are helpful for lowering cesarean section rate and the incidences of fetal macrosomia, fetal distress, and neonatal asphyxia and ensuring the health of mothers and infants.%目的 探讨GDM孕妇孕前体质量指数及孕期体质量指数增加对分娩方式

  14. Hyperekplexia in neonates

    OpenAIRE

    V. Praveen; Patole, S; Whitehall, J

    2001-01-01

    Hyperekplexia (startle disease) is a rare non-epileptic disorder characterised by an exaggerated persistent startle reaction to unexpected auditory, somatosensory and visual stimuli, generalised muscular rigidity, and nocturnal myoclonus. The genetic basis is a mutation usually of the arginine residue 271 leading to neuronal hyperexcitability by impairing glycinergic inhibition. Hyperekplexia is usually familial, most often autosomal dominant with complete penetrance and variable expression. ...

  15. Radiologic findings of neonatal sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of); Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong [Sansung Medical Center, Seoul (Korea, Republic of)

    1997-06-01

    To review the simple radiographic and sonographic findings in infants with neonatal sepsis. We retrospectively analyzed simple chest and abdominal radiographs, and brain sonograms in 36 newborn infants (preterm : term=23 :13). With neonatal sepsis diagnosed by blood culture and clinical manifestations. Pulmonary parenchymal infiltrate excluding respiratory distress syndrome and pulmonary edema or atelectasis was found in 22 infants (61%). Paralytic ileus, hepatosplenomegaly, and necrotizing enterocolitis were present in 18(50%), 9(25%), and 1(3%) infants, respectively, while skeletal changes suggesting osteomyelitis were found in three. Brain sonography was performed in 29 infants and in four, abnormalities were seen ; these comprised three germinal matrix hemorrhages and one intraparenchymal hemorrhage. In six patients(17%) radiologic examinations revealed no abnormality. In patients with neonatal sepsis, pulmonary infiltrates and paralytic ileus were common abnormalities. Although these were nonspecific, radiologic findings may be used to supplement clinical and laboratory findings in diagnosing neonatal sepsis and planning its treatment.

  16. Pseudothrombocytopenia in a preterm neonate.

    Science.gov (United States)

    Christensen, Robert D; Sola, Martha C; Rimsza, Lisa M; McMahan, Michael J; Calhoun, Darlene A

    2004-07-01

    Severe and prolonged thrombocytopenia is not uncommon among ill preterm infants. Pseudothrombocytopenia, which has the appearance of severe and prolonged thrombocytopenia, has not been described in this population. We observed a preterm neonate who had EDTA-independent pseudothrombocytopenia and conclude that this condition should be considered when severe and prolonged thrombocytopenia occurs in a neonate in the absence of clinical signs of platelet-type hemorrhage.

  17. 一个新的肝细胞核因子1α基因突变致青少年的成人起病型糖尿病3型家系报道%A novel hepatocyte nuclear factor-1α genetic mutation in a Chinese pedigree with maturity-onset diabetes of the young type 3

    Institute of Scientific and Technical Information of China (English)

    王天平; 张淼; 时立新; 杨雨星

    2014-01-01

    Objective To determine the genetic basis of maturity-onset diabetes of the young in a Chinese pedigree.Methods A 32 years old female patient was noticed that there were two generations of the family with diabetes.The pathogenic gene in the proband was identified by target area capture deep sequencing,and then was verified and screened the genetic mutation in the proband and other family members by Sanger sequencing.Results A new heterozygous frameshift mutation in hepatocyte nuclear factor-1α(HFN-1α) located in the exon 6 (c.1130-1131insC; p.V380Cfs * 39) was identified.The mutation was co-segregated with diabetes.Conclusion A novel HNF-1α genetic mutation in a Chinese pedigree with MODY3 is found.%目的 探讨一个青少年的成人起病型糖尿病(MODY)家系的致病基因.方法 对一例发病9年的32岁女性糖尿病患者家系成员进行调查,该家系中有两代糖尿病患者,采用目标区域捕获高深度测序技术在先证者中找到突变基因,使用Sanger测序技术验证突变位点并筛查其他家系成员.结果 基因检测发现家系中3个个体携带肝细胞核因子1α(HNF-1α)基因V380Cfs* 39移码突变,该突变在家系中表现为与糖尿病共分离.结论 该家系为一个新的HNF-1α基因突变所致MODY3家系.

  18. Neonatal Sepsis and Inflammatory Mediators

    Science.gov (United States)

    Reis Machado, Juliana; Soave, Danilo Figueiredo; da Silva, Marcos Vinícius; de Menezes, Liliana Borges; Etchebehere, Renata Margarida; Monteiro, Maria Luiza Gonçalves dos Reis; Antônia dos Reis, Marlene; Corrêa, Rosana Rosa Miranda; Celes, Mara Rúbia Nunes

    2014-01-01

    Neonatal sepsis is a major cause of morbidity and mortality and its signs and symptoms are nonspecific, which makes the diagnosis difficult. The routinely used laboratory tests are not effective methods of analysis, as they are extremely nonspecific and often cause inappropriate use of antibiotics. Sepsis is the result of an infection associated with a systemic inflammatory response with production and release of a wide range of inflammatory mediators. Cytokines are potent inflammatory mediators and their serum levels are increased during infections, so changes from other inflammatory effector molecules may occur. Although proinflammatory and anti-inflammatory cytokines have been identified as probable markers of neonatal infection, in order to characterize the inflammatory response during sepsis, it is necessary to analyze a panel of cytokines and not only the measurement of individual cytokines. Measurements of inflammatory mediators bring new options for diagnosing and following up neonatal sepsis, thus enabling early treatment and, as a result, increased neonatal survival. By taking into account the magnitude of neonatal sepsis, the aim of this review is to address the role of cytokines in the pathogenesis of neonatal sepsis and its value as a diagnostic criterion. PMID:25614712

  19. diabetic patients

    Directory of Open Access Journals (Sweden)

    Mehraban Falahati

    2016-09-01

    candiduria and female gender, high FBS and urine glucose, uncontrolled diabetes (HbA1c ≥8, and acidic urine pH (P<0.05. Conclusion: Considering the high incidence rate of candiduria in diabetic patients, control of diabetes, predisposing factors, and causal relationships between diabetes and candiduria should be highlighted.

  20. [Diabetic neuropathy].

    Science.gov (United States)

    Lechleitner, Monika; Abrahamian, Heidemarie; Francesconi, Claudia; Kofler, Markus

    2016-04-01

    These are the guidelines for diagnosis and treatment of diabetic neuropathy. This diabetic late complication comprises a number of mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy. The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided.

  1. A novel c.197T ® A variant among Brazilian neonates with glucose-6-phosphate dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    José Pereira de Moura Neto

    2008-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49 deficiency is the most common enzyme deficiency worldwide, causing a spectrum of diseases including neonatal hyperbilirubinemia and acute or chronic hemolysis. We used the methemoglobin reduction test and G6PD electrophoresis to screen 655 neonates (354 females and 301 males for common G6PD mutations in the city of Salvador in the Northeastern Brazilian state Bahia and found that 66 (10.1% were G6PD-deficient (41 females and 25 males. The 66 (10.1% G6PD-deficient neonates were assessed for the c.376 A -> G (exon 5 and c.202 G -> A (exon 4 mutations using the polymerase chain reaction and restriction enzyme fragment length polymorphism (PCR-RFLP analysis and the results validated by DNA sequencing. Of the 66 G6PD-deficient neonates investigated we found that 54 (81.8% presented the c.376 A -> G (p.Asn126Asp and c.202 G -> A (p.Val68Met mutations, two (3% had the c.376 A -> G mutation only, two (3% had the c.202 G -> A mutation only, five (7.6% exhibited a previously unrecorded 197T -> A (p.Phe66Thr substitution in exon 4 and three showed no mutations at any of these sites. Of the five neonates exhibiting the new 197T -> A (p.Phe66Thr substitution, four (6.1% also presented the c.202 G -> A and c.376 A -> G mutations and one (1.5% had the c.[197T -> A / 202 G -> A] combination. We propose to name the new variant G6PD Bahia.

  2. Neonatal erythroderma as a first manifestation of Menkes disease.

    Science.gov (United States)

    Galve, Javier; Vicente, Asunción; González-Enseñat, María Antonia; Pérez-Dueñas, Belén; Cusí, Victoria; Møller, Lisbeth Birk; Julià, Marc; Domínguez, Anna; Ferrando, Juan

    2012-07-01

    Menkes disease is an X-linked recessive lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration, connective tissue disturbances, and peculiar kinky hair are the main manifestations. The low serum copper and ceruloplasmin suggests the diagnosis, which is confirmed by mutation analysis of the ATP7A gene. We report an exceptional presentation of classic Menkes disease with neonatal erythroderma. Genetic study revealed a deletion in exons 8 to 12 in the ATP7A gene. This study could allow pediatricians and pediatric dermatologists to diagnose the disorder as early as possible to establish prompt treatment with parenteral copper-histidine supplementation to improve prognosis.

  3. Tyrosinemia Type III detected via neonatal screening: management and outcome.

    Science.gov (United States)

    Heylen, Evelyne; Scherer, Gerd; Vincent, Marie-Françoise; Marie, Sandrine; Fischer, Judith; Nassogne, Marie-Cécile

    2012-11-01

    Tyrosinemia Type III is caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), an enzyme involved in the catabolic pathway of tyrosine. To our knowledge, only a few patients presenting with this disease have been described in the literature, and the clinical phenotype remains variable and unclear. We report the case of a boy with tyrosinemia Type III detected using neonatal screening, who is homozygous for the splice donor mutation IVS11+1G>A in intron 11 of the HPD gene. At the age of 30 months, the boy's outcome under mild protein restriction was characterized by normal growth and psychomotor development.

  4. INVISIBLE MURDERER: NEONATAL TETANUS

    Directory of Open Access Journals (Sweden)

    Yonca SONMEZ

    2006-06-01

    Full Text Available Neonatal tetanus (NNT has been secondary in the whole world in the death list of diseases which can be protected by the help of vaccine. It’s an important community health problem in the less-developed countries in which pre-birth care services are limited, assisting a mother at childbirth by uneducated people in dirty atmosphere and the immunity against tetanus is not enough. Studies have shown that minor part of the cases have been expressed in most of the countries. Because of that NNT have been called as “silent/invisible murderer”. In Turkey, in the year of 2003 it has been seen 15 cases, and 12 of them have been resulted in death. The methods which will be applied to carry out the elimination of NNT are; the vaccination of pregnant women with at least two doses tetanus toxoid and providing clean birth conditions for all of the pregnant women. However, in Turkey the proportion of the women who have two doses of tetanus vaccine is 41%. To eliminate NNT in our country, all the pregnant women must be attained, the ones who are attained must be presented with qualified pre-birth care service which also includes tetanus immunity and the births must be carried out under healty conditions. As smallpox and polio eradication, NNT elimination will also be accomplished by self-sacrificing works of personnel in primary health care. [TAF Prev Med Bull 2006; 5(3.000: 229-233

  5. Porcine Neonatal Coccidiosis

    Science.gov (United States)

    Sanford, S. E.; Josephson, G. K. A.

    1981-01-01

    Coccidia were identified in intestinal sections from 82 piglets comprising 37 consignments from 34 farms, and represented a yearly increasing incidence in the three years 1978 to 1980. Piglets were primarily from medium to large farms with intensive, continuous-farrowing, confinement-rearing programs. Piglets, usually five days to 15 days old, had yellow, fluid diarrhea, became unthrifty and sometimes died. In six piglets from two farms, a green, adherent, fibrinonecrotic membrane was seen throughout most of the jejunum and ileum. Significant gross lesions were not observed in the other 76 piglets. Moderate to severe villous atrophy of jejunum and ileum was seen histologically. Various asexual and sexual stages of coccidia were seen within parasitophorous vacuoles of villar epithelial cells. Multifocal erosions with necrosis of villar tips and occasionally more diffuse mucosal necrosis with fibrinocellular exudate were seen. Isospora suis oocysts were identified in feces from several weaners from one farm. Amprolium and decoquinate mixed in the sow ration at 1 kg/tonne for three weeks prior to and postfarrowing was moderately successful in stopping outbreaks of neonatal diarrhea associated with coccidiosis. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:7343074

  6. Neonatal invasive candidiasis.

    Science.gov (United States)

    Stronati, M; Decembrino, L

    2006-12-01

    Over the last two decades, systemic fungal infections have emerged to play a primary role in hospital-acquired infections. C. albicans is involved in 75% of neonatal candidiasis; however, the incidence of infection from C. parapsilosis is also increasing significantly. The higher incidence observed in the high-risk group of very low birth weight (VLBW) infants is linked to their special physical characteristics and the diagnostic and therapeutic invasive procedures they undergo. Colonization is a relevant risk factor depending on the colonized site , the fungal species and the type of colonization. Serological tests have a low specificity and sensitivity; in many cases, they do not distinguish between colonization and infection. Blood culture, although the best diagnostic test for determining systemic infection, can result negative, even in cases of deep organ involvement. In addition, fungi grow more slowly than bacteria in cultures. So, the difficulty in diagnosing systemic candidiasis and its aspecific clinical features may make empirical therapy appropriate. Amphotericin B (AmB) alone or combined with 5-fluorocytosine remains the drug of choice. Fluconazole represents a valid alternative. Recently developed new formulations of amphotericin incapsulated in liposomes can avoid possible adverse effects. Prognosis depends on the specific micro-organism involved; mortality is higher in the presence of C. albicans. As prognosis is associated with high mortality, prevention measures to reduce risk factors are of critical importance.

  7. CF Mutation Panel

    Science.gov (United States)

    ... Testing; Cystic Fibrosis Transmembrane Conductance Regulator Mutation Analysis; CFTR Mutation Analysis Formal name: Cystic Fibrosis Gene Mutation ... an elevated immunoreactive trypsinogen (IRT) or positive sweat chloride test , to confirm the diagnosis of cystic fibrosis. ...

  8. Missense mutations of the fibrillin-1 gene in two Chinese patients with severe Marfan syndrome

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To describe two Chinese patients with severe forms of Marfan syndrome and to report findings of mutational analysis of the fibrillin-1 (FBN1) gene.Methods Two Chinese patients were studied, one suffering from Marfan syndrome of infantile onset and the other of neonatal onset. Their clinical features were described. Mutational analysis of the FBN1 gene was performed using polymerase chain reaction (PCR) technique and direct sequencing of exons 23 - 32,where the mutational hotspots for severe forms of Marfan syndrome are located.Results Two missense mutations were successfully identified, a G3037A transition and an A3083T transversion, the latter being an unreported mutation.Conclusion Taking advantage of the clustering phenomenon of mutations in severe forms of Marfan syndrome, one can identify FBN1 mutations in these patients by first screening the mutational hotspots,thus reducing the effort that would otherwise be much greater because of the size of the gene.

  9. Pregnancy in PCOS women and their history of diabetes

    DEFF Research Database (Denmark)

    Viftrup-Lund, Mette; Gade, Melina; Lauszus, Finn

    2014-01-01

    Objective: Evaluation of the incidence of gestational diabetes in PCOS women treated with metformin before and during early pregnancy and to ascertain their family history of diabetes. Design: Follow-up on all women with PCOS and infertility who received treatment with metformin prior to pregnancy...... (=index pregnancy) during 10 years. Data on diabetes was retrieved by questionnaire and hospital charts. Main outcome measures: Incidence of gestational diabetes, pregnancy outcome, and fetal size Results: In 18 % of the women GDM was diagnosed at some stage. The clinical and obstetrical outcome...... of the women showed no association with family history of diabetes or GDM. No neonatal anthropometric feature was different with respect to family history of diabetes or GDM and no fetal malformations were found Conclusion: GDM and family history of diabetes seem not to be associated with unfavourable...

  10. BRAF V600E-Positive Multisite Langerhans Cell Histiocytosis in a Preterm Neonate

    Directory of Open Access Journals (Sweden)

    Sara V. Bates

    2013-10-01

    Full Text Available Hemorrhagic pustules with a “blueberry muffin” appearance accompanied by respiratory failure in a neonate present a challenging differential diagnosis that includes infections and neoplasms. We present a case of multiorgan, multisite Langerhans cell histiocytosis (LCH, positive for the oncogenic BRAF V600E mutation, in a preterm neonate. Infants with LCH pose a diagnostic challenge due to their heterogeneous presentations. This case is unusual in that the newborn presented with severe multiorgan involvement. Due to the rare incidence, wide spectrum of clinical manifestations, and high mortality rate, clinicians must maintain a high index of suspicion for LCH.

  11. Bacterial Culture of Neonatal Sepsis

    Directory of Open Access Journals (Sweden)

    AH Movahedian

    2006-08-01

    Full Text Available Neonatal bacterial sepsis is one of the major cause of morbidity and mortality in neonates. This retrospective study was performed to determine the incidence of bacterial sepsis with focus on Gram negative organisms in neonates admitted at Beheshti Hospital in Kashan, during a 3-yr period, from September 2002 to September 2005. Blood culture was performed on all neonates with risk factors or signs of suggestive sepsis. Blood samples were cultured using brain heart infusion (BHI broth according to standard method. From the 1680 neonates 36% had positive blood culture for Pseudomans aeruginosa, 20.7% for Coagulase negative Staphylococci, and 17% for Klebsiella spp. Gram-negative organisms accounted for 72.1% of all positive cultures. The overall mortality rate was 19.8% (22 /111 of whom 63.6% (14 /22 were preterm. Pseudomona aeruginosa and Klebsiella spp. showed a high degree of resistance to commonly used antibiotics (ampicillin, gentamicin as well as third generation cephalosporins. Continued local surveillance studies are urged to monitor emerging antimicrobial resistance and to guide interventions to minimize its occurrence.

  12. Nem toda criança diabética é tipo 1 Not every diabetic child has type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Thais Della Manna

    2007-11-01

    Full Text Available OBJETIVO: Apesar de o diabetes melito tipo 1 de origem autoimune ser o mais prevalente na infância e adolescência, outras formas de diabetes também podem acometer essa população, implicando em prognóstico e tratamentos diferentes. FONTES DOS DADOS: Foram utilizadas informações através de revisão bibliográfica realizada por busca direta de artigos científicos nas bases de dados MEDLINE e LILACS, além de publicações clássicas referentes ao tema, sendo escolhidas as mais representativas. SÍNTESE DOS DADOS: Este artigo discute os mecanismos fisiopatológicos, quadro clínico e tratamento das diversas formas de diabetes que acometem a faixa etária pediátrica, como diabetes melito tipo 1, diabetes melito tipo 2, diabetes do tipo maturity-onset diabetes of youth, diabetes neonatal, diabetes mitocondrial, diabetes da lipodistrofia generalizada, diabetes secundário a outras pancreatopatias, diabetes secundário a outras endocrinopatias, diabetes associado a infecções e drogas citotóxicas e diabetes relacionado a algumas síndromes genéticas. CONCLUSÃO: O reconhecimento do mecanismo fisiopatológico primário da forma de diabetes apresentada pode orientar seu tratamento específico, otimizando seu controle metabólico e minimizando suas complicações a longo prazo.OBJECTIVE:Although it is type 1 diabetes mellitus of autoimmune origin that is most prevalent in childhood and adolescence, other forms of diabetes can also affect this population, resulting in different prognosis and treatment. SOURCES: Information was obtained by means of a bibliographic review, carried out by running searches for scientific articles in the MEDLINE and LILACS databases, in addition to classic publications on the subject, with the most representative being chosen. SUMMARY OF THE FINDINGS: This article discusses the pathophysiological mechanisms, clinical presentation and treatment of the various forms of diabetes that affect the pediatric age group

  13. The Effects of Increased Maternal Visual Regard of Neonate Upon the Neonate-Mother Interaction.

    Science.gov (United States)

    Belcastro, Christina M.; And Others

    This study attempts to investigate the effects of increased maternal visual regard on neonatal social visual behavior and upon patterns of mother-neonate interaction within the context of a learning theory paradigm. Subjects were 3-day-old neonates and their mothers; with 10 of the 15 mother-neonate pairs as the experimental group, and 5 as the…

  14. [Diabetes mellitus].

    Science.gov (United States)

    Ahdi, M; Gerdes, V E A; Hoekstra, J B L; Meesters, E W

    2012-02-01

    Currently there are over 740,000 patients with diabetes mellitus in the Netherlands, and this number will increase further in the coming years. Approximately 90% of patients has type 2 diabetes, a metabolic disorder that is often associated with obesity, hypertension and increased cholesterol levels. Treatment of diabetes mellitus is essential to reduce the risk of severe complications with irreversible organ damage in the long-term. Gingivitis and periodontitis are more common in patients with diabetes mellitus and are now also considered as complications of diabetes. Collaboration among healthcare professionals is important for effective diabetes care.

  15. Pregnancy outcomes in youth with type 2 diabetes: The TODAY Study experience

    Science.gov (United States)

    We evaluated pregnancy outcomes, maternal and fetal/neonatal, during the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. The TODAY study was a randomized controlled trial comparing three treatment options for youth with type 2 diabetes. Informed consent included the req...

  16. A Rare Cause of Neonatal Liver Failure: Neonatal Hemochromatosis

    Directory of Open Access Journals (Sweden)

    Uluca Ü et al.

    2013-09-01

    Full Text Available Neonatal hemochromatosis (NH is a severe rare liver disease in neonatal period associated with ekstrahepatic siderosis. This disease is characterized by hepatocellular insufficiency that presented with jaundice, hypoglycemia, hypoalbuminemia, low fibrinogen levels, thrombocytopenia, anemia, direct and indirect hyperbilirubinemia from the first days of life. Herein we reported a case with Rh incompatibility whose jaundice was noted at the first day of life and referred to our hospital for exchange transfusion, but thereafter diagnosed as NH and reviewed the literature in the view point of the latest developments related to the topic.

  17. Neonatal pressure ulcers: prevention and treatment

    National Research Council Canada - National Science Library

    García-Molina P; Alfaro-López A; García-Rodríguez SM; Brotons-Payá C; Rodríguez-Dolz MC; Balaguer-López E

    2017-01-01

    .... Neonates often suffer from diaper rash or intravenous drugs extravasation. Recently, hospitalized neonates and especially those in an unstable clinical situation are also at a risk of developing pressure ulcers...

  18. A multistate population-based analysis of linked maternal and neonatal discharge records to identify risk factors for neonatal brachial plexus injury.

    Science.gov (United States)

    Freeman, Michael D; Goodyear, Shaun M; Leith, Wendy M

    2017-03-01

    To evaluate the interaction and contribution of maternal and fetal risk factors associated with neonatal brachial plexus injury (BPI). In a case-control study, matched maternal and neonatal discharge records were accessed from US State Inpatient Databases for New Jersey (2010-2012), Michigan (2010-2011), and Hawaii (2010-2011). Univariate and multivariate logistic regressions were used to evaluate associations between risk factors and BPI. Area under the receiver operating characteristic curve was used to build predictive models, including two stratified models evaluating deliveries among obese and diabetic cohorts. Among 376 325 deliveries, BPI was diagnosed in 274 (0.1%). Significant BPI risk factors included maternal obesity (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.7-4.4), maternal diabetes (OR 4.6, 95% CI 3.0-7.0), use of forceps (OR 4.6, 95% CI 2.3-9.0), and vacuum assistance (OR 2.3, 95% CI 1.7-3.3). After adjusting for shoulder dystocia and other predictive factors, cesarean reduced the risk of BPI by 88% (OR 0.1, 95% CI 0.07-0.2). When stratified by obesity and diabetes, the ORs for BPI increased significantly for macrosomia, forceps, and vacuum assistance. The analysis confirms and quantifies more precisely the impact of risk factors for neonatal BPI, and provides a reliable basis for evidence-based clinical decision-making models. © 2016 International Federation of Gynecology and Obstetrics.

  19. Fetal and neonatal thyrotoxicosis

    Directory of Open Access Journals (Sweden)

    Chandar Mohan Batra

    2013-01-01

    Full Text Available Fetal thyrotoxicosis is a rare disease occurring in 1 out of 70 pregnancies with Grave′s disease or in 1 out of 4000-50,000 deliveries. The mortality is 12-20%, usually from heart failure, but other complications are tracheal compression, infections and thrombocytopenia. It results from transfer of thyroid stimulating immunoglobulins from mother to fetus through the placenta. This transplacental transfer begins around 20 th week of pregnancy and reaches its maximum by 30 th week. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH receptors and increase the secretion of the thyroid hormones. The mother has an active autoimmune thyroid disease or has been treated for it in the past. She may be absolutely euthyroid due to past treatment by drugs, surgery or radioiodine ablation, but still have active TSH receptor stimulating autoantibodies, which can cause fetal thyrotoxicosis. The other features of this disease are fetal tachycardia, fetal goiter and history of spontaneous abortions and findings of goiter, ascites, craniosyntosis, fetal growth retardation, maceration and hydrops at fetal autopsy. If untreated, this disease can result in intrauterine death. The treatment for this disease consists of giving carbimazole to the mother, which is transferred through the placenta to the fetus. The dose of carbimazole is titrated with the fetal heart rate. If the mother becomes hypothyroid due to carbimazole, thyroxine is added taking advantage of the fact that very little of thyroxine is transferred across the placenta. Neonatal thyrotoxicosis patients are very sick and require emergency treatment. The goal of the treatment is to normalize thyroid functions as quickly as possible, to avoid iatrogenic hypothyroidism while providing management and supportive therapy for the infant′s specific signs and symptoms.

  20. Maternal and neonatal health outcomes following assisted reproduction.

    Science.gov (United States)

    Farhi, A; Reic