Maternal phenylketonuria: Embryotoxicity in vitro of PKU-related metabolites and of human PKU-sera

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Piersma AH; Verhoef A; Hamers AM; van den Ham WA; Jansen EHJM

1993-01-01

Mothers with untreated phenylketonuria (PKU) have an increased risk of bearing children with congenital malformations. PKU causes accumulation of phenylalanine (PHE) and its metabolites in urine and blood, and this condition may contribute to the developmental problems. In the present study we

Syndromes, Disorders and Maternal Risk Factors Associated With Neural Tube Defects (VII

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Chih-Ping Chen

2008-09-01

Full Text Available Neural tube defects (NTDs may be associated with syndromes, disorders and maternal risk factors. This article provides a comprehensive review of the syndromes, disorders and maternal risk factors associated with NTDs, including DK phocomelia syndrome (von Voss-Cherstvoy syndrome, Siegel-Bartlet syndrome, fetal warfarin syndrome, craniotelencephalic dysplasia, Czeizel-Losonci syndrome, maternal cocaine abuse, Weissenbacher-Zweymüller syndrome, parietal foramina (cranium bifidum, Apert syndrome, craniomicromelic syndrome, XX-agonadism with multiple dysraphic lesions including omphalocele and NTDs, Fryns microphthalmia syndrome, Gershoni-Baruch syndrome, PHAVER syndrome, periconceptional vitamin B6 deficiency, and autosomal dominant Dandy-Walker malformation with occipital cephalocele. NTDs associated with these syndromes, disorders and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders and maternal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (I

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Chih-Ping Chen

2008-03-01

Full Text Available Fetuses with neural tube defects (NTDs maybe associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as acrocallosal syndrome, autosomal dominant brachydactyly-clinodactyly syndrome, Manouvrier syndrome, short rib-polydactyly syndrome, Disorganization (Ds-like human malformations, isolated hemihyper-plasia, X-linked NTDs, meroanencephaly, schisis association, diprosopus, fetal valproate syndrome, DiGeorge syndrome/velocardiofacial syndrome, Waardenburg syndrome, folic acid antagonists, diabetes mellitus, and obesity. NTDs associated with syndromes, disorders, and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

Syndromes, disorders and maternal risk factors associated with neural tube defects (I).

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Chen, Chih-Ping

2008-03-01

Fetuses with neural tube defects (NTDs) may be associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as acrocallosal syndrome, autosomal dominant brachydactyly-clinodactyly syndrome, Manouvrier syndrome, short rib-polydactyly syndrome, Disorganization ( Ds )-like human malformations, isolated hemihyperplasia, X-linked NTDs, meroanencephaly, schisis association, diprosopus, fetal valproate syndrome, DiGeorge syndrome/velocardiofacial syndrome, Waardenburg syndrome, folic acid antagonists, diabetes mellitus, and obesity. NTDs associated with syndromes, disorders, and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

Epidemiologic view of phenylketonuria (PKU in Latinamerica

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Gustavo JC Borrajo

2014-07-01

Phenylketonuria newborn screening programs vary among different Latin American countries; each one has its own history; quality standards, newborn population covered and the mandatory legislation of newborn screening. Epidemiological knowledge on phenylketonuria of this region is imprecise due to the lack of national statistic registries, thus avoiding an objective assessment of population coverage and disease incidence; therefore available data is obtained from isolated observations. Analysis of phenylketonuria and hyperphenylalaninemia based on available information of several Latin American newborn screening programs shows mean incidence values of 1: 23,518 and 1: 20,759 respectively; however, individual analysis of incidence by country indicates that phenylketonuria ranges between 1:12,473 and 1:161,748 live newborns.

Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (II

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Chih-Ping Chen

2008-03-01

Full Text Available Fetuses with neural tube defects (NTDs maybe associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as Currarino syndrome, sacral defect with anterior meningocele, Jarcho-Levin syndrome (spondylo-costal dysostosis, lateral meningocele syndrome, neurofibromatosis type I, Marfan syndrome, and hyperthermia. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

Neurological images in phenylketonuria (PKU

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Juan Francisco Cabello

2014-07-01

Full Text Available Phenylketonuria is an inborn error of metabolism that causes structural abnormalities in the white matter of the brain. In untreated patients demyelization can be observed, and there is evidence of intramyelin edema even in some treated patients. Imaging studies especially magnetic resonance imaging are useful for the study of patients with phenylketonuria, but their benefit as monitoring tools is controversial.

[Diagnostics and treatment of phenylketonuria].

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Bayat, Allan; Møller, Libeth Birk; Lund, Allan Meldgaard

2015-02-16

Primary phenylalanine hydroxylase deficiency, also known as phenylketonuria, results in accumulation of phenylalanine in the blood. Early identification and treatment prevents the majority of clinical sequelae to the disease, but psychological and neurodevelopmental problems can occur in some patients. This article reviews the symptoms, diagnosis, classification and strategies of treatment and management of phenylketonuria. Finally we review new pharmacological and non-pharmaco-logical means of treatment.

Syndromes, Disorders and Maternal Risk Factors Associated With Neural Tube Defects (VI

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Chih-Ping Chen

2008-09-01

Full Text Available Neural tube defects (NTDs may be associated with syndromes, disorders, and maternal and fetal risk factors. This article provides a comprehensive review of the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, including maternal fumonisin consumption, periconceptional zinc deficiency, parental occupational exposure and residential proximity to pesticides, lower socioeconomic status, fetal alcohol syndrome, mutations in the VANGL1 gene, human athymic Nude/SCID fetus, and single nucleotide polymorphism in the NOS3 gene. NTDs associated with these syndromes, disorders, and maternal and fetal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

Asymmetric dimethylarginine in children with homocystinuria or phenylketonuria.

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Kanzelmeyer, Nele; Tsikas, Dimitrios; Chobanyan-Jürgens, Kristine; Beckmann, Bibiana; Vaske, Bernhard; Illsinger, Sabine; Das, Anibh M; Lücke, Thomas

2012-05-01

Plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis from L-arginine and a cardiovascular risk factor, was found to be elevated in plasma of homocysteinemic adults. Enhanced cardiovascular risk due to homocystinuria and impaired renal function has been found in patients with phenylketonuria (PKU) on protein-restricted diet. However, it is still unknown whether ADMA synthesis is also elevated in children with homocystinuria due to cystathionine beta-synthase deficiency (classical homocystinuria), and whether ADMA may play a role in phenylketonuria in childhood. In the present study, we investigated the status of the L-arginine/NO pathway in six young patients with homocystinuria, in 52 young phenylketonuria patients on natural protein-restricted diet, and in age- and gender-matched healthy children serving as controls. ADMA in plasma and urine was determined by GC-MS/MS. The NO metabolites nitrate and nitrite in plasma and urine, and urinary dimethylamine (DMA), the dimethylarginine dimethylaminohydrolase (DDAH) metabolite of ADMA, were measured by GC-MS. Unlike urine ADMA excretion, plasma ADMA concentration in patients with homocystinuria was significantly higher than in controls (660±158 vs. 475±77 nM, P=0.035). DMA excretion rate was considerably higher in children with homocystinuria as compared to controls (62.2±24.5 vs. 6.5±2.9 μmol/mmol creatinine, P=0.068), indicating enhanced DDAH activity in this disease. In contrast and unexpectedly, phenylketonuria patients had significantly lower ADMA plasma concentrations compared to controls (512±136 vs. 585±125 nM, P=0.009). Phenylketonuria patients and controls had similar L-arginine/ADMA molar ratios in plasma. Urinary nitrite excretion was significantly higher in phenylketonuria as compared to healthy controls (1.7±1.7 vs. 0.7±1.2 μmol/mmol creatinine, P=0.003). Our study shows that the L-arginine/NO pathway is differently altered in children

Epidemiologic study of Phenylketonuria disease in Lorestan province

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Azita Zafar Mohtashami

2016-12-01

Full Text Available Background : Phenylketonuria (PKU is a metabolic disease with autosomal recessive pattern of inheritance caused by a deficiency or absence of the enzyme phenylalanine hydroxylase in the liver. Phenylketonuria incidence is 1 in 10,000 births. This study aimed to determine the epidemiological characteristics of phenylketonuria in Lorestan province. Materials and Methods: All 81 phenylketonuria patients known in Lorestan province up to winter 2014 were considered in this descriptive epidemiologic study. Based on the goals and variables of the study, a complete questionnaire was developed to collect data through interviews with parents and the records and they were analyzed by use of SPSS v.16 software with preparing tables and graphs and using chi-square and t-test. Results: Results showed that phenylketonuria prevalence is 4.3 out of 100,000 people in Lorestan province. Twenty of the patients (24.7% were identified through screening and 61 patients (75.3% through other methods. Forty-six of the samples (56.8% were female and 35 cases (43.2% were male. Nearly 75% of PKU patients had a positive history of consanguinity marriage in their parents. The prevalence of the disease was significantly different from other cities. Conclusion: Neonatal screening for phenylketonuria is necessary and should be done within 3-5 days of birth. In families with children suffering from PKU, prenatal diagnosis is necessary for other pregnancies.

Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (III

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Chih-Ping Chen

2008-06-01

Full Text Available Fetuses with neural tube defects (NTDs may be associated with syndromes, disorders, and maternal and fetal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal and fetal risk factors associated with NTDs, such as omphalocele, OEIS (omphalocele-exstrophy-imperforate anus-spinal defects complex, pentalogy of Cantrell, amniotic band sequence, limb-body wall complex, Meckel syndrome, Joubert syndrome, skeletal dysplasia, diabetic embryopathy, and single nucleotide polymorphisms in genes of glucose metabolism. NTDs associated with syndromes, disorders, and maternal and fetal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multi facto rial NTDs. Perinatal identification of NTDs should alert the clinician to the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling. [Taiwan J Obstet Cynecol 2008;47(2:131-140

Review of neonatal screening programme for phenylketonuria.

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Smith, I; Cook, B; Beasley, M

1991-01-01

OBJECTIVE--To review the neonatal screening programme during 1984-8. DESIGN--Analysis of data from screening laboratories and paediatricians. SUBJECTS--All live births in United Kingdom. MAIN OUTCOME MEASURES--Structure of programme; number of infants tested and number with phenylketonuria; number of infants missed; ages at testing and treatment. RESULTS--The proportion of infants tested approached 100%. The incidence of phenylketonuria was 11.7/100,000 births (445 subjects): 273 had classic phenylketonuria and three had defects of cofactor metabolism. One child with phenylketonuria was known to have been missed compared with three in 1979-83 and six in 1974-8. Seven subjects had been missed over the 15 years due to negative test results. All seven had been tested with the bacterial inhibition assay, although only 53% of infants had been so tested; the difference between the expected and observed proportion was significant (Fisher's exact test, p = 0.017). Eleven infants with classic phenylketonuria were not tested by 14 days of age and 23 (8%) did not start treatment until after 20 days, an improvement compared with 36 (15%) in 1979-83. There were, however, wide regional variations (0% to 27% treated after 20 days). CONCLUSION--The screening programme achieves high coverage and effectiveness, although some children are still missed. A national practice for screening may help reduce regional variations. PMID:1912773

Prenatal Maternal Smoking and Tourette Syndrome: A Nationwide Register Study.

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Leivonen, Susanna; Chudal, Roshan; Joelsson, Petteri; Ekblad, Mikael; Suominen, Auli; Brown, Alan S; Gissler, Mika; Voutilainen, Arja; Sourander, Andre

2016-02-01

This is the first nationwide register-based study to examine the relationship between prenatal maternal smoking and Tourette syndrome. A total of 767 children diagnosed with Tourette syndrome were identified from the Finnish Hospital Discharge Register. Each case was matched to four controls. Information on maternal smoking during pregnancy was obtained from the Finnish Medical Birth Register. Conditional logistic regression models were used for statistical analyses. Prenatal maternal smoking was associated with Tourette syndrome when comorbid with ADHD (OR 4.0, 95 % CI 1.2-13.5, p = 0.027 for exposure during first trimester, OR 1.7, 95 % CI, 1.05-2.7, p = 0.031 for exposure for the whole pregnancy). There was no association between maternal smoking during pregnancy and Tourette syndrome without comorbid ADHD (OR 0.5, 95 % CI 0.2-1.3, p = 0.166, OR 0.9, 95 % CI 0.7-1.3, p = 0.567). Further research is needed to elucidate the mechanisms behind the association between prenatal maternal smoking and Tourette syndrome with comorbid ADHD.

Maternal serum markers in screening for Down syndrome

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Nørgaard-Pedersen, B; Larsen, S O; Arends, J

1990-01-01

The addition of two new markers in maternal serum, estriol and HCG, to those already known, namely the level of maternal serum alfa-fetoprotein and maternal age, considerably improves the expected results of a screening strategy for Down syndrome. The detection rate is slightly increased from 53....

Phenylketonuria management from an European perspective : A commentary

NARCIS (Netherlands)

van Spronsen, Francjan J.

Phenylketonuria is discussed from an European perspective, addressing the need of common definitions of terms commonly used, the need of a world-wide guideline on the diagnosis and treatment of phenylketonuria, the differences between existing European guidelines, and day-to-day care, further

Phenylketonuria screening in the Republic of Macedonia.

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Kocova, Mirjana; Anastasovska, Violeta

2016-08-05

Phenylketonuria is an autosomal recessive inborn error of metabolism which can be prevented by early and continuous treatment. Therefore newborn screening for phenylketonuria has been introduced in many countries. We present here the results of the selective newborn screening for inborn errors of metabolism, including PKU, performed by tandem mass spectrometry which has been introduced in Macedonia since 2011.

Learning about Phenylketonuria (PKU)

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Skip to main content Learning About Phenylketonuria Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research News ...

Partial HELLP Syndrome: maternal and perinatal outcome

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Joelcio Francisco Abbade

Full Text Available CONTEXT: HELLP syndrome is a severe complication of pregnancy characterized by hemolysis, elevated liver enzymes and low platelet count. Some pregnant women develop just one or two of the characteristics of this syndrome, which is termed Partial HELLP Syndrome (PHS. OBJECTIVE: The objective of this study was to evaluate the repercussions on maternal and perinatal outcomes among women that developed PHS and to compare these women with those whose gestational hypertension or preeclampsia did not show alterations for HELLP syndrome in laboratory tests. DESIGN: Observational, retrospective and analytical study. SETTING: Maternity Department of Hospital das Clínicas, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil. SAMPLE: Pregnant or post-delivery women who had a blood pressure elevation that was first detected after mid-pregnancy, with or without proteinuria, between January 1990 and December 1995. MAIN MEASUREMENTS: Analysis was made of maternal age, race, parity, hypertension classification, gestational age at the PHS diagnosis, alterations in laboratory tests for HELLP syndrome, time elapsed to discharge from hospital, maternal complications, mode of delivery, incidence of preterm birth, intrauterine growth restriction, stillborn and neonatal death. RESULTS: Three hundred and eighteen women were selected; forty-one women (12.9% had PHS and 277 of them (87.1% did not develop any of the alterations of the HELLP syndrome diagnosis. Preeclampsia was a more frequent type of hypertension in the PHS group than in the hypertension group. None of the women with isolated chronic hypertension developed PHS. The rate of cesarean delivery, eclampsia, and preterm delivery was significantly greater in the PHS group than in the hypertension group. CONCLUSION: We observed that aggressive procedures had been adopted for patients with PHS. These resulted in immediate interruption of pregnancy, with elevated cesarean

Factors Influencing Verbal Intelligence and Spoken Language in Children with Phenylketonuria.

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Soleymani, Zahra; Keramati, Nasrin; Rohani, Farzaneh; Jalaei, Shohre

2015-05-01

To determine verbal intelligence and spoken language of children with phenylketonuria and to study the effect of age at diagnosis and phenylalanine plasma level on these abilities. Cross-sectional. Children with phenylketonuria were recruited from pediatric hospitals in 2012. Normal control subjects were recruited from kindergartens in Tehran. 30 phenylketonuria and 42 control subjects aged 4-6.5 years. Skills were compared between 3 phenylketonuria groups categorized by age at diagnosis/treatment, and between the phenylketonuria and control groups. Scores on Wechsler Preschool and Primary Scale of Intelligence for verbal and total intelligence, and Test of Language Development-Primary, third edition for spoken language, listening, speaking, semantics, syntax, and organization. The performance of control subjects was significantly better than that of early-treated subjects for all composite quotients from Test of Language Development and verbal intelligence (Pphenylketonuria subjects.

Importância do diagnóstico e tratamento da fenilcetonúria Diagnoses and treatment of phenylketonuria

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Nádia VM de Mira

2000-02-01

Full Text Available A fenilcetonúria (PKU é o mais comum dos erros congênitos do metabolismo de aminoácidos. Resulta da deficiência da fenilalanina hidroxilase, enzima que catalisa a conversão de fenilalanina em tirosina. A introdução de uma dieta com baixo teor de fenilalanina deve ter início nos primeiros meses de vida, de preferência no primeiro mês, para evitar o retardo mental, manifestação clínica mais severa da doença. Foi elaborada revisão sobre essa temática, que aborda desde a PKU clássica até a hiperfenilalaninemia branda, incluindo relato sobre a PKU maternal e os efeitos da exposição do útero a altos níveis de fenilalanina sobre o feto.Phenylketonuria is the most common inborn error of amino acid metabolism. It is due to a deficiency of phenylalanine hydroxylase, which normally converts phenylalanine to tyrosine. A diet low in phenylalanine starting in the first month of life can significantly reduce mental retardation, the most important feature of the disease. The aim of the review is to discuss the difficulties found in the diagnosis of PKU and its variants, ranging from classic phenylketonuria to mild hyperphenylalaninaemia, and the effects of dietary restriction of phenylalanine on the growth and development of children. Also, we present the current controversies about the age of discontinuing the dietary treatment. This review summarizes the benefits and problems emerging from a prolonged therapy taking into account dietary compliance in different age groups, and discusses dietary alternatives to the synthetic amino acid mixtures free of phenylalanine, based on low phenylalanine protein hydrolysates. In addition, we show some information about the effects of maternal phenylketonuria on pregnancy outcome and infant development, if exposed to high phenylalanine levels intra uterineo.

Phenylketonuria in adulthood: a collaborative study.

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Koch, R; Burton, B; Hoganson, G; Peterson, R; Rhead, W; Rouse, B; Scott, R; Wolff, J; Stern, A M; Guttler, F; Nelson, M; de la Cruz, F; Coldwell, J; Erbe, R; Geraghty, M T; Shear, C; Thomas, J; Azen, C

2002-09-01

During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967-1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations. The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural

[Anxiety driven atypical eating disorder in the course of phenylketonuria].

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Rapps, Nora; Mack, Isabelle; Herrmann-Werner, Anne; Zipfel, Stephan; Teufel, Martin

2015-07-01

Phenylketonuria is the most common genetic disease in amino acid metabolism. We report the case of a 22-year old patient with phenylketonuria and psychological symptoms. After early treatment, phenylalanine levels had been controlled and were within target area. Clinical interview and psychometrics showed atypical eating disorder and anxiety disorder. Possible toxic effects and psychological factors may play a role in pathogenesis. Most likely the frequency of eating disorders and anxiety disorders in phenylketonuria is underestimated. © Georg Thieme Verlag KG Stuttgart · New York.

Maternal irradiation and Down Syndrome

International Nuclear Information System (INIS)

Gibson, D.L.; Uh, S.H.; Miller, J.R.

1978-04-01

The role of preconception irradiation in the etiology of Down Syndrome was examined using the techniques of record linkage. Although 909 cases of Down Syndrome, born in B.C. between 1952-70, were ascertained through a system of linked vital and health registrations, interest was restricted to the 348 case/control pairs born in the greater Vancouver area. The maternal identifying information routinely recorded on birth and ill-health registrations was used to link 155 Down Syndrome mothers and 116 control mothers to patient files at the Vancouver General Hospital. Only 28 of the case and 25 of the control mothers were subjected to diagnostic irradiation at the Vancouver Ganeral Hospital. The difference was not significant at the 5% level

Review of neuropsychological functioning in treated phenylketonuria: an information processing approach.

Science.gov (United States)

Waisbren, S E; Brown, M J; de Sonneville, L M; Levy, H L

1994-12-01

Phenylketonuria is no longer associated with mental retardation and other devastating neurological effects. Nonetheless, learning disabilities and IQ loss are common, even in early-treated individuals. Until recently, IQ was used as the sole measure of mental functioning in this population. As specific academic deficits were recognized and as a greater variety of tests became available, evaluation of children with phenylketonuria has included neuropsychological testing. A review of the 21 published reports highlights the areas of consensus and the need for additional well designed studies in the future. Problem solving, particularly abstract reasoning and executive functions, appears to be impaired in children with phenylketonuria. Reaction time, or speed of mental processing, appears to be the other important area affected in PKU. An information processing model is presented as a paradigm for further research and development of remedial strategies for children with phenylketonuria.

The Electro-Encephalogram in Phenylketonuria

Science.gov (United States)

Todd, Peter G.; Pitt, D. B.

1973-01-01

Evaluated were electroencephalographic findings in 24 untreated (ages from 4 to 38 years) patients suffereing from phenylketonuria (a metabolic disorder producing severe mental retardation if not treated with proper diet during the early years). (DB)

MODERN PRINCIPLES OF DIET ORGANIZATION IN CHILDREN IN DIFFERENT AGE WITH PHENYLKETONURIA

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T.V. Bushuyeva

2010-01-01

Full Text Available The article reports questions of diet organization in children with phenylketonuria in different age with the use of modern specialized food. Authors give examples of calculation of diet based on new norms of needs in energy and food for different groups of population in Russian Federation, and present recommendations on optimization of nutrition in schoolchildren with phenylketonuria.Key words: children, schoolchildren, phenylketonuria, phenylalanine, dietotherapy.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(2:124-129

Use of sapropterin in the management of phenylketonuria

DEFF Research Database (Denmark)

Gokmen Ozel, H; Lammardo, A M; Motzfeldt, K

2013-01-01

Sapropterin treatment, with or without dietary treatment, improves blood phenylalanine control, increases phenylalanine tolerance, and may reduce the day-to-day dietary treatment burden in a subset of patients with phenylketonuria (PKU). Balancing the need for maintained control of blood phenylal......Sapropterin treatment, with or without dietary treatment, improves blood phenylalanine control, increases phenylalanine tolerance, and may reduce the day-to-day dietary treatment burden in a subset of patients with phenylketonuria (PKU). Balancing the need for maintained control of blood...

Cranial CT and MRI in malignant phenylketonuria

Energy Technology Data Exchange (ETDEWEB)

Gudinchet, F.; Maeder, P.; Meuli, R.A. (CHUV, Lausanne (Switzerland). Dept. of Radiology); Deonna, T.; Mathieu, J.M. (CHUV, Lausanne (Switzerland). Dept. of Pediatrics)

1992-06-01

Malignant phenylketonuria is a rare disease caused by a deficiency in dihydropteridine-reductase which induce a hyperphenylalaninemia and a defiency of neurotransmitters such as 3,4, dihydroxyphenylalanine (DOPA) and 5 hydroxytriphtophan. The case of a patient with malignant phenylketonuria (PKU) who underwent both CT and MR Imaging is reported. CT demonstrated the characteristic calcifications of the basal ganglia. MRI demonstrated areas of hypersignal on T1 and images in the basal ganglia, subcortical frontal and occipital white matter and cortex probably corresponding to clacifications. The MR findings are not specific but could be useful in monitoring the diet and neurotransmitter substitution therapy. (orig.).

Cranial CT and MRI in malignant phenylketonuria

International Nuclear Information System (INIS)

Gudinchet, F.; Maeder, P.; Meuli, R.A.; Deonna, T.; Mathieu, J.M.

1992-01-01

Malignant phenylketonuria is a rare disease caused by a deficiency in dihydropteridine-reductase which induce a hyperphenylalaninemia and a defiency of neurotransmitters such as 3,4, dihydroxyphenylalanine (DOPA) and 5 hydroxytriphtophan. The case of a patient with malignant phenylketonuria (PKU) who underwent both CT and MR Imaging is reported. CT demonstrated the characteristic calcifications of the basal ganglia. MRI demonstrated areas of hypersignal on T1 and images in the basal ganglia, subcortical frontal and occipital white matter and cortex probably corresponding to clacifications. The MR findings are not specific but could be useful in monitoring the diet and neurotransmitter substitution therapy. (orig.)

Phenylketonuria

International Nuclear Information System (INIS)

Pearsen, K.D.; Gean-Marton, A.D.; Levy, H.L.; Davis, K.R.

1989-01-01

Phenylketonuria (PKU) is an autosomal, recessive, inborn error of phenylalanine metabolism. Without diet treatment, PKU leads to mental retardation as well as demyelimation, gliosis, and spongiosis of the white matter. This paper reports cerebral MR imaging prospectively performed on 16 PKU patients (ages, 8-35; IQ levels, 20-120; diet-history range, treated since infancy to no treatment). MR images revealed a spectrum of subtle to advanced demyelination of the posterior periventricular white matter, with frontal lobe involvement in severe cases, but no structural or posterior fossa abnormalities in any cases. No reliable correlation was found, either between MR abnormalities and intelligence or between MR abnormalities and diet history

The challenges of managing coexistent disorders with phenylketonuria

DEFF Research Database (Denmark)

MacDonald, A; Ahring, K; Almeida, M F

2015-01-01

INTRODUCTION: The few published case reports of co-existent disease with phenylketonuria (PKU) are mainly genetic and familial conditions from consanguineous marriages. The clinical and demographic features of 30 subjects with PKU and co-existent conditions were described in this multi-centre, re......INTRODUCTION: The few published case reports of co-existent disease with phenylketonuria (PKU) are mainly genetic and familial conditions from consanguineous marriages. The clinical and demographic features of 30 subjects with PKU and co-existent conditions were described in this multi...

Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings

DEFF Research Database (Denmark)

Boonen, Susanne E; Pörksen, Sven; Mackay, Deborah Jg

2008-01-01

We present the first clinical report of sibs with the multiple maternal hypomethylation syndrome. Both sisters presented with transient neonatal diabetes mellitus (TNDM). By methylation-specific PCR of bisulphite-treated DNA, we found a mosaic spectrum of hypomethylation at the following maternal...

Maternal Pseudo-Bartter Syndrome Associated with Severe Perinatal Brain Injury.

Science.gov (United States)

Vora, Shrenik; Ibrahim, Thowfique; Rajadurai, Victor Samuel

2017-09-15

Maternal electrolyte imbalance is rarely reported as causative factor of severe perinatal brain injury. This case outlines a unique maternal and neonatal pseudo-Bartter syndrome presented with metabolic alkalosis and hypochloremia due to maternal severe vomiting. Neonatal MRI brain revealed extensive brain hemorrhages with porencephalic cysts. Subsequent investigation workup points towards maternal severe metabolic alkalosis as its cause. Careful medical attention should be paid to pregnant women with excessive vomiting to ensure a healthy outcome for both the mother and the baby.

Classic Phenylketonuria: Diagnosis Through Heterozygote Detection

Science.gov (United States)

Griffin, Robert F.; Elsas, Louis J.

1975-01-01

In an attempt to improve the identification of the asymptomatic carrier of classic phenylketonuria (PKU) 59 male and female normal control Ss were differentiated from 18 males and females heterozgous for PKU. (DB)

PHENYLKETONURIA, A COMPREHENSIVE BIBLIOGRAPHY, 1964.

Science.gov (United States)

Children's Bureau (DHEW), Washington, DC.

INTENDED AS AN AID TO PROFESSIONAL AND TECHNICAL PERSONS INTERESTED IN PHENYLKETONURIA (PKU), THE BIBLIOGRAPHY LISTS AND ANNOTATES 817 ITEMS. CONTENT DIVISIONS ARE (1) GENERAL--MONOGRAPHS AND ARTICLES, (2) BIOCHEMISTRY--METABOLISM, EXPERIMENTS, TESTS, AND CASES IN WHICH THE EMPHASIS IS ON BIOCHEMISTRY, (3) GENETICS--GENE STUDIES, HEREDITARY…

NUTRITIONAL KNOWLEDGE IN PHENYLKETONURIA (PKU

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Beatriz D. O. MIRANDA DA CRUZ

2009-07-01

Full Text Available

ABSTRACT: A review of phenylketonuria (PKU an autosomal recessive genetic desorder discovered and described in 1934 is presented and discussed. Excess phenylalanine is transamined and its presence or metabolites may cause brain damage. Hydroxylation is the most important determinant of phenylalanine homeostasis in humans. It has been shown a great geographic and ethnic variation in the presence of PKU. Neonatal screening is the main method to detect babies with this desorder. Restriction of phenylalanine intake is the most effective PKU treatment. There are several well balanced commercial formulas low in this amino acid. They should be introduced as soon as the positive PKU test is confirmed and be kept for a long time. Present knowledge allows the possibility of pregnancy of PKU girls, under dietary control. Alternative treatments have been proposed for PKU and great advance has lately been achieved on the genetic and nutricional aspects of the disease. KEYWORDS: Phenylketonuria; children; phenylalanine, nutrition PKU.

[Phenotypic and molecular characterization of a Colombian family with phenylketonuria].

Science.gov (United States)

Gélvez, Nancy; Acosta, Johana; López, Greizy; Castro, Derly; Prieto, Juan Carlos; Bermúdez, Martha; Tamayo, Marta L

2016-09-01

Phenylketonuria is a metabolic disorder characterized by severe neurological involvement and behavioral disorder, whose early diagnosis enables an effective treatment to avoid disease sequelae, thus changing the prognosis. Objective: To characterize a family with phenylketonuria in Colombia at clinical, biochemical and molecular levels. Materials and methods: The population consisted of seven individuals of a consanguineous family with four children with suggestive symptoms of phenylketonuria. After signing an informed consent, blood and urine samples were taken for colorimetric tests and high performance liquid and thin layer chromatographies. DNA extraction and sequencing of the 13 exons of the PAH gene were performed in all subjects. We designed primers for each exon with the Primer 3 software using automatic sequencing equipment Abiprism 3100 Avant. Sequences were analyzed using the SeqScape, v2.0, software. Results: We described the clinical and molecular characteristics of a Colombian family with phenylketonuria and confirmed the presence of the mutation c.398_401delATCA. We established a genotype-phenotype correlation, highlighting the interesting clinical variability found among the affected patients despite having the same mutation in all of them. Conclusions: Early recognition of this disease is very important to prevent its neurological and psychological sequelae, given that patients reach old age without diagnosis or proper management.

Cognitive profile and mental health in adult phenylketonuria: A PKU-COBESO study.

Science.gov (United States)

Jahja, Rianne; Huijbregts, Stephan C J; de Sonneville, Leo M J; van der Meere, Jaap J; Legemaat, Amanda M; Bosch, Annet M; Hollak, Carla E M; Rubio-Gozalbo, M Estela; Brouwers, Martijn C G J; Hofstede, Floris C; de Vries, Maaike C; Janssen, Mirian C H; van der Ploeg, Ans T; Langendonk, Janneke G; van Spronsen, Francjan J

2017-05-01

Despite early dietary treatment phenylketonuria patients have lower IQ and poorer executive functions compared to healthy controls. Cognitive problems in phenylketonuria have often been associated with phenylalanine levels. The present study examined the cognitive profile and mental health in adult phenylketonuria, in relation to phenylalanine levels and tetrahydrobiopterin treatment. Fifty-seven early treated adult patients with phenylketonuria and 57 healthy matched controls (18-40 years) performed IQ subtests and executive function tests from the Amsterdam Neuropsychological Tasks. They also completed the Adult Self-Report on mental health problems. Analyses of variance were performed to examine group differences. Patients with phenylketonuria had normal IQs although lower than controls. They performed poorer on working memory, inhibitory control, and sustained attention tasks. Patients reported Depressive and Avoidant Personality problems more frequently. Specifically, patients with childhood and lifetime phenylalanine ≥360 μmol/L had poorer cognitive and mental health outcomes than controls. In a subset of patients, comparisons between patients on and off tetrahydrobiopterin showed that nontetrahydrobiopterin users (matched for childhood, pretreatment phenylalanine) were slower (on number of tasks) and reported more mental health problems. Adult patients had lower IQ and poorer executive functions than controls, resembling problems observed in younger patients with phenylketonuria, as well as more internalizing problems. Group differences and phenylalanine-outcome associations were smaller than those observed in younger populations. A subset of nontetrahydrobiopterin users, matched for childhood phenylalanine level, had a poorer outcome on some tests than tetrahydrobiopterin users, which might indicate an impact of tetrahydrobiopterin treatment beyond lowering phenylalanine. However, clinical relevance needs further investigation. (PsycINFO Database Record

Maternal Burnout Syndrome: Contextual and Psychological Associated Factors

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Astrid Lebert-Charron

2018-06-01

Full Text Available Background: Becoming a parent is one of the most significant experiences in a woman’s life. Including substantial and long-lasting mental, social, and physical charge, the parenting experience may also be a potentially stressful and overwhelming task. Since the eighties, the notion of parental burnout syndrome has gained increasing attention, but its contextual and psychological factors need to be better identified.Aims: To investigate a large array of contextual and psychological factors associated with maternal burnout syndrome in a French community-based population in order to contribute to better operationalize the notion of parental burnout and to explore its determinants.Method: A total of 304 French-speaking mothers (mean age = 34.8 years, SD = 6.72 completed a set of questionnaires including a sociodemographic form (in order to gather general information about the mothers, their spouses, and children living at home. The Perceived Stress Scale, the Maslach Burnout Inventory adapted to parents (MBI-parental, the Hospital Anxiety and Depression Scale, the Parental Stress Index-Short Form and the Ways of Coping Checklist were used in this study.Results: Multivariate linear regression analyses revealed that scores on the MBI-parental version were strongly and positively associated with depressive and anxiety symptoms, as well as with perceived stress related to parenthood and parenting stress levels. Moreover, using the task-oriented coping style in parenthood was strongly and positively associated with personal accomplishment. Conversely, some sociodemographic characteristics were found to be negatively associated with maternal burnout: being employed, working full time and being a mother living without a coparent.Conclusion: The construct of maternal burnout syndrome seems to be linked to a conjunction of psychological and contextual factors associated with maternal exhaustion. The implication of the results for prevention and

Maternal Burnout Syndrome: Contextual and Psychological Associated Factors

Science.gov (United States)

Lebert-Charron, Astrid; Dorard, Géraldine; Boujut, Emilie; Wendland, Jaqueline

2018-01-01

Background: Becoming a parent is one of the most significant experiences in a woman’s life. Including substantial and long-lasting mental, social, and physical charge, the parenting experience may also be a potentially stressful and overwhelming task. Since the eighties, the notion of parental burnout syndrome has gained increasing attention, but its contextual and psychological factors need to be better identified. Aims: To investigate a large array of contextual and psychological factors associated with maternal burnout syndrome in a French community-based population in order to contribute to better operationalize the notion of parental burnout and to explore its determinants. Method: A total of 304 French-speaking mothers (mean age = 34.8 years, SD = 6.72) completed a set of questionnaires including a sociodemographic form (in order to gather general information about the mothers, their spouses, and children living at home). The Perceived Stress Scale, the Maslach Burnout Inventory adapted to parents (MBI-parental), the Hospital Anxiety and Depression Scale, the Parental Stress Index-Short Form and the Ways of Coping Checklist were used in this study. Results: Multivariate linear regression analyses revealed that scores on the MBI-parental version were strongly and positively associated with depressive and anxiety symptoms, as well as with perceived stress related to parenthood and parenting stress levels. Moreover, using the task-oriented coping style in parenthood was strongly and positively associated with personal accomplishment. Conversely, some sociodemographic characteristics were found to be negatively associated with maternal burnout: being employed, working full time and being a mother living without a coparent. Conclusion: The construct of maternal burnout syndrome seems to be linked to a conjunction of psychological and contextual factors associated with maternal exhaustion. The implication of the results for prevention and intervention strategies

Early-Treated Phenylketonuria: Neuropsychologic Consequences.

Science.gov (United States)

Brunner, Robert L.; And Others

1983-01-01

The neuropsychologic performance of 27 children (about 6 to 13 years old) with early-treated phenylketonuria (PKU) was evaluated and correlated with their serum phenylalanine concentrations at several ages. (Author/SEW) Journal Availability: The Journal of Pediatrics; The C. V. Mosby Company, 11830 Westline Industrial Drive, St. Louis, MO 63141.

The Role of Maternal Dietary Proteins in Development of Metabolic Syndrome in Offspring

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Alireza Jahan-Mihan

2015-11-01

Full Text Available The prevalence of metabolic syndrome and obesity has been increasing. Pre-natal environment has been suggested as a factor influencing the risk of metabolic syndrome in adulthood. Both observational and experimental studies showed that maternal diet is a major modifier of the development of regulatory systems in the offspring in utero and post-natally. Both protein content and source in maternal diet influence pre- and early post-natal development. High and low protein dams’ diets have detrimental effect on body weight, blood pressure191 and metabolic and intake regulatory systems in the offspring. Moreover, the role of the source of protein in a nutritionally adequate maternal diet in programming of food intake regulatory system, body weight, glucose metabolism and blood pressure in offspring is studied. However, underlying mechanisms are still elusive. The purpose of this review is to examine the current literature related to the role of proteins in maternal diets in development of characteristics of the metabolic syndrome in offspring.

Diffusion MRI findings in phenylketonuria

International Nuclear Information System (INIS)

Sener, R.N.

2003-01-01

Two patients with phenylketonuria were studied who were under dietary control since infancy, and who were mentally normal. Diffusion MRI was obtained using a spin-echo, echo-planar sequence with a gradient strength of 30 mT/m at 1.5 T. A trace sequence (TR=5700 ms, and TE=139 ms) was used, acquired in 22 s. Heavily diffusion-weighted (b=1000 mm 2 /s) images, and the apparent diffusion coefficient (ADC) values from automatically generated ADC maps were studied. There were two different patterns in these two patients, restricted and increased diffusion patterns. Restricted diffusion pattern consisted of high-signal on b=1000 s/mm 2 images with low ADC values ranging from 0.46 to 0.57 x 10 -3 mm 2 /s. Increased diffusion pattern consisted of normal b=1000 s/mm 2 images with high ADC values ranging from 1.37 to 1.63 x 10 -3 mm 2 /s. It is likely that these values reflected presence of two different histopathological changes in phenylketonuria or reflected different stages of the same disease. (orig.)

Maternal obesity and high-fat diet program offspring metabolic syndrome.

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Desai, Mina; Jellyman, Juanita K; Han, Guang; Beall, Marie; Lane, Robert H; Ross, Michael G

2014-09-01

We determined the potential programming effects of maternal obesity and high-fat (HF) diet during pregnancy and/or lactation on offspring metabolic syndrome. A rat model of maternal obesity was created using an HF diet prior to and throughout pregnancy and lactation. At birth, pups were cross-fostered, thereby generating 4 paradigms of maternal diets during pregnancy/lactation: (1) control (Con) diet during pregnancy and lactation (Con/Con), (2) HF during pregnancy and lactation (HF/HF), (3) HF during pregnancy alone (HF/Con), and (4) HF during lactation alone (Con/HF). Maternal phenotype during pregnancy and the end of lactation evidenced markedly elevated body fat and plasma corticosterone levels in HF dams. In the offspring, the maternal HF diet during pregnancy alone programmed increased offspring adiposity, although with normal body weight, whereas the maternal HF diet during lactation increased both body weight and adiposity. Metabolic disturbances, particularly that of hyperglycemia, were apparent in all groups exposed to the maternal HF diet (during pregnancy and/or lactation), although differences were apparent in the manifestation of insulin resistant vs insulin-deficient phenotypes. Elevated systolic blood pressure was manifest in all groups, implying that exposure to an obese/HF environment is disadvantageous for offspring health, regardless of pregnancy or lactation periods. Nonetheless, the underlying mechanism may differ because offspring that experienced in utero HF exposure had increased corticosterone levels. Maternal obesity/HF diet has a marked impact on offspring body composition and the risk of metabolic syndrome was dependent on the period of exposure during pregnancy and/or lactation. Copyright © 2014 Mosby, Inc. All rights reserved.

Influences on maternal responsivity in mothers of children with fragile X syndrome

OpenAIRE

Sterling, Audra M.; Warren, Steven F.; Brady, Nancy; Fleming, Kandace

2013-01-01

This study investigated the influence of maternal and child variables on the maternal responsivity of 55 mothers with young children with fragile X syndrome. Data included video observations of maternal-child interactions in four different contexts, standardized assessments with the children, and standardized questionnaires for the mothers. The video observations were coded for child communication acts; maternal responsivity was coded at two levels: a more general measure and a behavior-by-be...

Early dietary treated patients with phenylketonuria can achieve normal growth and body composition.

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Rocha, Júlio C; van Spronsen, Francjan J; Almeida, Manuela F; Ramos, Elisabete; Guimarães, João T; Borges, Nuno

2013-01-01

In the past, overtreatment may have resulted in growth impairment in patients with phenylketonuria. The paper aims to investigate height and body composition in early treated patients with phenylketonuria who were diagnosed between 1981 and 2008. A cross-sectional study of 89 patients with phenylketonuria and 78 controls aged (mean ± SD, in years) 14.4 ± 6.6 and 15.9 ± 7.1, respectively, was undertaken, including anthropometric and body composition evaluation using bioelectrical impedance. Median Phe concentrations in the last year before study enrollment were used as a measure of metabolic control. Natural protein and amino acid mixture intakes were recorded in patients. No statistically significant differences were found on height z-scores between patients and controls aged less than 19 years (p=0.301), although all patients with classical phenylketonuria revealed negative height z-scores, resulting in a mean ± SD of -0.65 ± 0.41. Among participants aged 19 years or more, median (p25-p75) of height was significantly higher in controls [168.0 cm (159.2-174.8)] than in patients [160.5 cm (151.9-167.5)] (p=0.017). No significant differences were found between patients and controls regarding fat mass, fat free mass, muscular mass, body cell mass index and phase angle. Our results suggest that early and continuously treated patients with phenylketonuria born after 1992 can achieve normal growth and body composition, although the negative height z-score in patients with classical phenylketonuria strengthens the continuous need to optimize the quality of their protein intake. © 2013 Elsevier Inc. All rights reserved.

Visual functions in phenylketonuria-evaluating the dopamine and long-chain polyunsaturated fatty acids depletion hypotheses.

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Gramer, Gwendolyn; Förl, Birgit; Springer, Christina; Weimer, Petra; Haege, Gisela; Mackensen, Friederike; Müller, Edith; Völcker, Hans Eberhard; Hoffmann, Georg Friedrich; Lindner, Martin; Krastel, Hermann; Burgard, Peter

2013-01-01

In phenylketonuria presymptomatic treatment following newborn screening prevents severe mental and physical impairment. The reasons for subtle impairments of cerebral functions despite early treatment remain unclear. We assessed a broad spectrum of visual functions in early-treated patients with phenylketonuria and evaluated two hypotheses-the dopamine and the long-chain polyunsaturated fatty acids (LCPUFAs) depletion hypotheses. Contrast sensitivity, colour vision, electroretinography, frequency doubling technology campimetry (FDT), and their relation with blood phenylalanine and docosahexaenoic acid levels were assessed in 36 patients with phenylketonuria and 18 age-matched healthy controls. Contrast sensitivity was significantly lower and total error scores in colour vision significantly higher in patients than controls. Electroretinography results differed significantly between patients and controls. We found a trend for the effect of phenylalanine-levels on contrast sensitivity and a significant effect on colour vision/FDT results. Docosahexaenoic acid levels in erythrocytes were not associated with visual functions. This is the first evaluation of visual functions in phenylketonuria using a comprehensive ophthalmological test battery. We found no evidence supporting the long-chain polyunsaturated fatty acids depletion hypothesis. However, the effect of phenylalanine-levels on visual functions suggests that imbalance between phenylalanine and tyrosine may affect retinal dopamine levels in phenylketonuria. This is supported by the similar patterns of visual functions in patients with phenylketonuria observed in our study and patients with Parkinson's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Assessment of brain phenylalanine dynamics in phenylketonuria patients

International Nuclear Information System (INIS)

Bik-Multanowski, M.; Pietrzyk, J. J.; Pasowicz, M.; Banys, R.P.

2006-01-01

Phenylketonuria (PKU) is the most common inborn error of metabolism in man. Brain phenylalanine kinetics can determine neurological treatment outcome in phenylketonuria. The aim of our study wa sto test a simplified magnetic resonance spectroscopy method for assessment of brain phenylalanine dynamics in PKU patients. Brain phenylalanine concentration (measured by means of magnetic resonance spectroscopy) and blood phenylalanine concentrations changes occurring within 24 hours after oral phenylalanine loading were analyzed in 5 PKU patients. The brain/blood phenylalanine ratio in 3 persons with normal intelligence was lower than in 2 with borderline intelligence or mild mental retardation. In our opinion the proposed method could be useful for assessment of brain phenylalanine dynamics in PKU patients. (author)

A current view of the diagnostics and treatment of phenylketonuria in Slovakia

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Ürge Oto

2015-12-01

Full Text Available An overview of the diagnostics and treatment of phenylketonuria in Slovakia is presented in this paper. The nature of diseases, incidence and prevalence in Slovakia, its genetic characteristics, current laboratory diagnostics and treatment options are defined. A new method of phenylketonuria screening in Slovakia, which has brought substantial improvement in early detection of the disease and shortening time for definitive diagnosis since 1995 as well as the importance of a tandem MS/MS (mass spectrometry introduced in the diagnosis of inherited metabolic disorders, is presented. The current state of phenylketonuria treatment focusing on low-protein dietary treatment and supplementation of amino acid mixtures is analysed. The use of sapropterin, enzyme replacement therapy, large neutral amino acids supplementation and gene therapy are also discussed.

Management of Newborn Infants with Phenylketonuria.

Science.gov (United States)

Health Services Administration (DHEW/PHS), Rockville, MD. Bureau of Community Health Services.

The booklet covers the identification, diagnosis, and clinical treatment of newborns with Phenylketonuria (PKU), an inborn error of metabolism, which, if untreated, can lead to mental retardation. An initial section considers biochemical and genetic factors of PKU including a diagram of aromatic amino acid hydroxylation systems. Screening…

Maternal risk factors predicting child physical characteristics and dysmorphology in fetal alcohol syndrome and partial fetal alcohol syndrome.

Science.gov (United States)

May, Philip A; Tabachnick, Barbara G; Gossage, J Phillip; Kalberg, Wendy O; Marais, Anna-Susan; Robinson, Luther K; Manning, Melanie; Buckley, David; Hoyme, H Eugene

2011-12-01

Previous research in South Africa revealed very high rates of fetal alcohol syndrome (FAS), of 46-89 per 1000 among young children. Maternal and child data from studies in this community summarize the multiple predictors of FAS and partial fetal alcohol syndrome (PFAS). Sequential regression was employed to examine influences on child physical characteristics and dysmorphology from four categories of maternal traits: physical, demographic, childbearing, and drinking. Then, a structural equation model (SEM) was constructed to predict influences on child physical characteristics. Individual sequential regressions revealed that maternal drinking measures were the most powerful predictors of a child's physical anomalies (R² = .30, p < .001), followed by maternal demographics (R² = .24, p < .001), maternal physical characteristics (R²=.15, p < .001), and childbearing variables (R² = .06, p < .001). The SEM utilized both individual variables and the four composite categories of maternal traits to predict a set of child physical characteristics, including a total dysmorphology score. As predicted, drinking behavior is a relatively strong predictor of child physical characteristics (β = 0.61, p < .001), even when all other maternal risk variables are included; higher levels of drinking predict child physical anomalies. Overall, the SEM model explains 62% of the variance in child physical anomalies. As expected, drinking variables explain the most variance. But this highly controlled estimation of multiple effects also reveals a significant contribution played by maternal demographics and, to a lesser degree, maternal physical and childbearing variables. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Comparison of atherogenic risk factors among poorly controlled and well-controlled adolescent phenylketonuria patients.

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Gündüz, Mehmet; Çakar, Sevim; Kuyum, Pınar; Makay, Balahan; Arslan, Nur

2016-06-01

Previous studies investigating the known risk factors of atherosclerosis in phenylketonuria patients have shown conflicting results. The primary aim of our study was to investigate the serum atherogenic markers in adolescent classical phenylketonuria patients and compare these parameters with healthy peers. The secondary aim was to compare these atherogenic markers in well-controlled and poorly controlled patients. A total of 59 patients (median age: 12.6 years, range: 11-17 years) and 44 healthy controls (median age: 12.0 years, range: 11-15 years) were enrolled in our study. Phenylketonuria patients were divided into two groups: well-controlled (serum phenylalanine levels below 360 µmol/L; 24 patients) and poorly controlled patients (serum phenylalanine levels higher than 360 µmol/L). The mean high-density lipoprotein cholesterol levels of well-controlled patients (1.0±0.2 mmol/L) were significantly lower compared with poorly controlled patients and controls (1.1±0.2 mmol/L, p=0.011 and 1.4±0.2 mmol/L, pphenylketonuria patients. In particular, these changes were more prominent in well-controlled patients. We conclude that phenylketonuria patients might be at risk for atherosclerosis, and therefore screening for atherosclerotic risk factors should be included in the phenylketonuria therapy and follow-up in addition to other parameters.

Distribution Occurrence of Phenylketonuria in the World: A Systematic Review and Meta-Analysis

Directory of Open Access Journals (Sweden)

Parastoo Moradi

2016-03-01

Full Text Available ​ Background and objectives : Phenylketonuria (PKU is a metabolic error which is caused by the deficiency of phenylalanine hydroxylase (PAH inverting phenylalanine to tyrosine. This disease is the most common form of hyperphenyalaninaemia stow which is inherited in a form of a predominant autosomal. Therefore, the aim of this study was to investigate the distribution of occurrence of phenylketonuria disease in the world by using the systematic review and meta-analysis. Material and Methods : The national and international databases such as Medline, CINAHL, Embase, PubMed and OVID, Google scholar, IranDOC, IranMedex, SID, Magiran, have been searched from 1990 onwards, without language restrictions and by using the key words: phenylketonuria, prevalence, incidence, congenital diseases. A total of 304 articles related with this topic were found. Finally, 62 studies were accepted. Data were analyzed by using Comprehensive Meta-Analysis software at 95% confidence level. The distribution of diseases was shown by using Geographic Information System software on the world map. Results : The findings showed that in 100000 people, the best estimate of the disease prevalence of phenylketonuria is 11.83 (95% CI: 10.22- 13.44 and the best estimate of the incidence of this disease is 8.2 (95% CI: 6.37- 10.03 in the world. The distribution of phenylketonuria disease has the highest rate in Europe and Asia and lowest rate in Africa and America, respectively. Conclusion : According to the findings of the present study, it can be said that there is a wide variety in the occurrence of phenylketonuria in the world and recent studies have confirmed his. Therefore, because of the irreversible consequences of the disease, the development of the appropriate training and control programs is recommended to reduce the occurrence of the disease.

PHENYLKETONURIA AND SOME ASPECTS OF EMOTIONAL DEVELOPMENT

NARCIS (Netherlands)

HENDRIKX, MMT; VANDERSCHOT, LWA; SLIJPER, FME; KALVERBOER, AF

1994-01-01

Early dietary treatment of phenylketonuria (PKU) prevents intellectual retardation and gross neurological impairment although not all neuropsychological problems. This study investigates to what extent the illness and its treatment imposes a burden on emotional development of early-treated PKU

A Current Look at Phenylketonuria (PKU).

Science.gov (United States)

Fischer, Margaret

Research was reviewed on the current status of phenylketonuria, an hereditary amino acid metabolic disorder that can cause severe mental retardation, physical complications, and emotional difficulties if not detected and treated early in childhood. A majority of the research cited was published in the 1960's. Topics covered were: discovery of…

Diffusion MRI findings in phenylketonuria

Energy Technology Data Exchange (ETDEWEB)

Sener, R.N. [Dept. of Radiology, Ege Univ. Hospital, Izmir (Turkey)

2003-12-01

Two patients with phenylketonuria were studied who were under dietary control since infancy, and who were mentally normal. Diffusion MRI was obtained using a spin-echo, echo-planar sequence with a gradient strength of 30 mT/m at 1.5 T. A trace sequence (TR=5700 ms, and TE=139 ms) was used, acquired in 22 s. Heavily diffusion-weighted (b=1000 mm{sup 2}/s) images, and the apparent diffusion coefficient (ADC) values from automatically generated ADC maps were studied. There were two different patterns in these two patients, restricted and increased diffusion patterns. Restricted diffusion pattern consisted of high-signal on b=1000 s/mm{sup 2} images with low ADC values ranging from 0.46 to 0.57 x 10{sup -3} mm{sup 2}/s. Increased diffusion pattern consisted of normal b=1000 s/mm{sup 2} images with high ADC values ranging from 1.37 to 1.63 x 10{sup -3} mm{sup 2}/s. It is likely that these values reflected presence of two different histopathological changes in phenylketonuria or reflected different stages of the same disease. (orig.)

Phenylketonuria : tyrosine supplementation in phenylalanine-restricted diets

NARCIS (Netherlands)

van Spronsen, FJ; van Rijn, M; Bekhof, J; Koch, R; Smit, PGA

Treatment of phenylketonuria (PKU) consists of restriction of natural protein and provision of a protein substitute that lacks phenylalanine but is enriched in tyrosine. Large and unexplained differences exist, however, in the tyrosine enrichment of the protein substitutes. Furthermore, some

Influences on Maternal Responsivity in Mothers of Children with Fragile X Syndrome

Science.gov (United States)

Sterling, Audra M.; Warren, Steven F.; Brady, Nancy; Fleming, Kandace

2013-01-01

This study investigated the influence of maternal and child variables on the maternal responsivity of 55 mothers with young children with fragile X syndrome. Data included video observations of mother-child interactions in four different contexts, standardized assessments with the children, and standardized questionnaires for the mothers. The…

Genetic Syndromes, Maternal Diseases and Antenatal Factors Associated with Autism Spectrum Disorders (ASD).

Science.gov (United States)

Ornoy, Asher; Weinstein-Fudim, Liza; Ergaz, Zivanit

2016-01-01

Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal, and postnatal etiologies. In addition, ASD is often an important clinical presentation of some well-known genetic syndromes in human. We discuss these syndromes as well as the role of the more important prenatal factors affecting the fetus throughout pregnancy which may also be associated with ASD. Among the genetic disorders we find Fragile X, Rett syndrome, tuberous sclerosis, Timothy syndrome, Phelan-McDermid syndrome, Hamartoma tumor syndrome, Prader-Willi and Angelman syndromes, and a few others. Among the maternal diseases in pregnancy associated with ASD are diabetes mellitus (PGDM and/or GDM), some maternal autoimmune diseases like antiphospholipid syndrome (APLS) with anti-β2GP1 IgG antibodies and thyroid disease with anti-thyroid peroxidase (TPO) antibodies, preeclampsia and some other autoimmune diseases with IgG antibodies that might affect fetal brain development. Other related factors are maternal infections (rubella and CMV with fetal brain injuries, and possibly Influenza with fever), prolonged fever and maternal inflammation, especially with changes in a variety of inflammatory cytokines and antibodies that cross the placenta and affect the fetal brain. Among the drugs are valproic acid, thalidomide, misoprostol, and possibly SSRIs. β2-adrenergic receptor agonists and paracetamol have also lately been associated with increased rate of ASD but the data is too preliminary and inconclusive. Associations were also described with ethanol, cocaine, and possibly heavy metals, heavy smoking, and folic acid deficiency. Recent studies show that heavy exposure to pesticides and air pollution, especially particulate matter ASD. Finally, we have to remember that many of the associations mentioned in this review are only partially proven, and not all are "clean" of different confounding factors. The

ADAM 12 as a second-trimester maternal serum marker in screening for Down syndrome

DEFF Research Database (Denmark)

Christiansen, Michael; Spencer, Kevin; Laigaard, Jennie

2007-01-01

ADAM 12 is a placenta-derived glycoprotein that is involved in growth and differentiation. The maternal serum concentration of ADAM 12 is a potential first-trimester maternal serum marker of Down syndrome (DS). Here we examine the potential of ADAM 12 as a second-trimester maternal serum marker...

Phenylketonuria : Tyrosine beyond the phenylalanine-restricted diet

NARCIS (Netherlands)

van Spronsen, FJ; Smit, PGA; Koch, R

Controversies exist on the role of tyrosine in the pathogenesis of phenylketonuria (PKU) and, consequently, on the therapeutic role of tyrosine. This review examines data and theoretical considerations on the role of tyrosine in the pathogenesis and treatment of PKU. It is concluded that treatment

Transcription is required to establish maternal imprinting at the Prader-Willi syndrome and Angelman syndrome locus.

Directory of Open Access Journals (Sweden)

Emily Y Smith

2011-12-01

Full Text Available The Prader-Willi syndrome (PWS [MIM 17620] and Angelman syndrome (AS [MIM 105830] locus is controlled by a bipartite imprinting center (IC consisting of the PWS-IC and the AS-IC. The most widely accepted model of IC function proposes that the PWS-IC activates gene expression from the paternal allele, while the AS-IC acts to epigenetically inactivate the PWS-IC on the maternal allele, thus silencing the paternally expressed genes. Gene order and imprinting patterns at the PWS/AS locus are well conserved from human to mouse; however, a murine AS-IC has yet to be identified. We investigated a potential regulatory role for transcription from the Snrpn alternative upstream exons in silencing the maternal allele using a murine transgene containing Snrpn and three upstream exons. This transgene displayed appropriate imprinted expression and epigenetic marks, demonstrating the presence of a functional AS-IC. Transcription of the upstream exons from the endogenous locus correlates with imprint establishment in oocytes, and this upstream exon expression pattern was conserved on the transgene. A transgene bearing targeted deletions of each of the three upstream exons exhibited loss of imprinting upon maternal transmission. These results support a model in which transcription from the Snrpn upstream exons directs the maternal imprint at the PWS-IC.

MR in phenylketonuria-related brain lesions

Czech Academy of Sciences Publication Activity Database

Dezortová, M.; Hájek, M.; Tintěra, J.; Hejcmanová, L.; Syková, Eva

2001-01-01

Roč. 42, - (2001), s. 459-466 ISSN 0284-1851 R&D Projects: GA ČR GV309/97/K048; GA ČR GA309/99/0657; GA MŠk VS96130 Institutional research plan: CEZ:AV0Z5039906 Keywords : brain phenylketonuria MR imaging Subject RIV: FH - Neurology Impact factor: 0.914, year: 2001

Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial12

Science.gov (United States)

Stroup, Bridget M; Clayton, Murray K; Murali, Sangita G; Rice, Gregory M; Rohr, Frances; Levy, Harvey L

2016-01-01

Background: To prevent cognitive impairment, phenylketonuria requires lifelong management of blood phenylalanine (Phe) concentration with a low-Phe diet. The diet restricts intake of Phe from natural proteins in combination with traditional amino acid medical foods (AA-MFs) or glycomacropeptide medical foods (GMP-MFs) that contain primarily intact protein and a small amount of Phe. Objective: We investigated the efficacy and safety of a low-Phe diet combined with GMP-MFs or AA-MFs providing the same quantity of protein equivalents in free-living subjects with phenylketonuria. Design: This 2-stage, randomized crossover trial included 30 early-treated phenylketonuria subjects (aged 15–49 y), 20 with classical and 10 with variant phenylketonuria. Subjects consumed, in random order for 3 wk each, their usual low-Phe diet combined with AA-MFs or GMP-MFs. The treatments were separated by a 3-wk washout with AA-MFs. Fasting plasma amino acid profiles, blood Phe concentrations, food records, and neuropsychological tests were obtained. Results: The frequency of medical food intake was higher with GMP-MFs than with AA-MFs. Subjects rated GMP-MFs as more acceptable than AA-MFs and noted improved gastrointestinal symptoms and less hunger with GMP-MFs. ANCOVA indicated no significant mean ± SE increase in plasma Phe (62 ± 40 μmol/L, P = 0.136), despite a significant increase in Phe intake from GMP-MFs (88 ± 6 mg Phe/d, P = 0.026). AA-MFs decreased plasma Phe (−85 ± 40 μmol/L, P = 0.044) with stable Phe intake. Blood concentrations of Phe across time were not significantly different (AA-MFs = 444 ± 34 μmol/L, GMP-MFs = 497 ± 34 μmol/L), suggesting similar Phe control. Results of the Behavior Rating Inventory of Executive Function were not significantly different. Conclusions: GMP-MFs provide a safe and acceptable option for the nutritional management of phenylketonuria. The greater acceptability and fewer side effects noted with GMP-MFs than with AA-MFs may enhance

Late-diagnosed phenylketonuria in an eight-year-old boy with dyslexia and attention-deficit hyperactivity disorder.

Science.gov (United States)

Yıldız, Yılmaz; Dursun, Ali; Tokatlı, Ayşegül; Coşkun, Turgay; Sivri, Hatice Serap

2016-01-01

Phenylketonuria, previously a common cause of severe intellectual disability, is a metabolic disorder now promptly diagnosed and effectively treated thanks to newborn screening programs. Here, we report a male patient presenting with dyslexia and attention-deficit hyperactivity disorder, who was diagnosed with mild phenylketonuria at eight years of age. Earlier recognition and treatment before the establishment of irreversible brain damage would have resulted in better neurobehavioural outcomes. Classical phenylketonuria and milder phenotypes of phenylalanine hydroxylase deficiency need to be considered in the differential diagnosis of all cognitive and behavioural problems of unknown cause.

[The clinical and molecular genetic characteristics of phenylketonuria patients in the Republic of Crimea].

Science.gov (United States)

Afanas'eva, N A; Bychkova, A M; Livshits, L A; Bariliak, I R

1998-01-01

The clinical and genetical characteristics of patients with phenylketonuria in the Crimean population is done in the present work. The comparison of clinical peculiarities of 28 patients, revealed by means of neonatal screening and that of 24 patients, the treatment of which was started late is presented. The prenatal diagnostics of 4 families with high phenylketonuria risk is conducted.

Physiological Correlates of Maternal Responsivity in Mothers of Preschoolers with Fragile X Syndrome

Science.gov (United States)

Robinson, Ashley N.; Roberts, Jane E.; Brady, Nancy C.; McQuillin, Samuel D.; Warren, Steven F.

2016-01-01

The present study examined the relationship between salivary cortisol and maternal responsiveness in mothers of boys with fragile X syndrome (FXS). Maternal responsivity is strongly associated with child outcomes, and children with FXS are at risk for compromised development due to intellectual disability and problem behavior. Increased…

Challenges and Pitfalls in the Management of Phenylketonuria

NARCIS (Netherlands)

Feillet, Francois; van Spronsen, Francjan J.; MacDonald, Anita; Trefz, Friedrich K.; Demirkol, Muebeccel; Giovannini, Marcello; Belanger-Quintana, Amaya; Blau, Nenad

Despite recent advances in the management of phenylketonuria and hyperphenylalaninemia, important questions on the management of this disorder remain unanswered. Consensus exists on the need for neonatal screening and early treatment, yet disagreement persists over threshold levels of blood

A late-diagnosed phenylketonuria case presenting with autism spectrum disorder in early childhood.

Science.gov (United States)

Mazlum, Betül; Anlar, Banu; Kalkanoğlu-Sivri, H Serap; Karlı-Oğuz, Kader; Özusta, Şeniz; Ünal, Fatih

2016-01-01

Phenylketonuria is one of the most prevalent autosomal recessive hereditary disorders in Turkey. If untreated, it results in severe brain damage and can also be associated with autism in certain patients. We present a three-year old boy who exhibited the symptoms of autism and was subsequently diagnosed with phenylketonuria. This case illustrates that because the majority of autism cases are idiopathic, an occasional patient with a metabolic disorder might be overlooked especially in the era of newborn screening. We also discuss the possible pathogenetic processes leading to autistic symptoms in phenylketonuria, and wish to draw attention to the possibility of cases missed in the screening program because of less than 100% coverage or insufficient food intake before blood sampling. Clinicians should keep in mind the possibility of treatable disorders in children with autism even when such disorders appear unlikely.

Maternal and foetal outcome in hellp syndrome at tertiary care hospital

International Nuclear Information System (INIS)

Sadaf, N.; Haq, G.; Din, S.S.U.

2013-01-01

Objective: To determine maternal and foetal outcome in patients of Haemolysis, Elevated Liver enzyme and Low Platelet Cont syndrome. Methods: The descriptive case series was conducted at the Gynae Unit II of Civil Hospital, Karachi, over a period of 12 months in two episodes; first from December 28, 2006, to February 28, 2007, and then from September 1, 2007, to June 30, 2008. It comprised 40 consecutive women with pre-ecampsia and eclampsia along with altered platelet count who met the syndrome criteria. A pre-designed proforma was administered for data collection. Maternal and foetal outcomes were noted. SPSS 10 was used for statistical analysis. Result: Among the 40 mothers, cesarean section was the most common outcome (n=24; 60%). Pulmonary oedema was found in 2 (5%) cases, acute renal failure in 10 (25%), disseminated intravascular coagulation in 6 (15%), and abruptio placenta in 5 (12.5%). Intrauterine growth restriction as a foetal outcome was observed in 18 (45%) cases. Pre-term birth was the result in 20 (50%) cases, and perinatal mortality was high (n=23; 57.5%). Conclusion: Management and delivery of HELLP syndrome patients should be performed at tertiary care centres, where highly trained obstetrician, neonatal intensive care unit personnel and Multi-disciplinary facilities are available. Correct diagnosis and timely intervention can decrease the risk of maternal and perinatal mortality. (author)

Weight Management in Phenylketonuria : What Should Be Monitored?

NARCIS (Netherlands)

Rocha, Julio Cesar; van Rijn, Margreet; van Dam, Esther; Ahring, Kirsten; Belanger-Quintana, Amaya; Dokoupil, Katharina; Ozel, Hulya Gokmen; Lammardo, Anna Maria; Robert, Martine; Heidenborg, Carina; MacDonald, Anita

2016-01-01

Background: Severe intellectual disability and growth impairment have been overcome by the success of early and continuous treatment of patients with phenylketonuria (PKU). However, there are some reports of obesity, particularly in women, suggesting that this may be an important comorbidity in PKU.

Phenylketonuria (PKU). ARC Q&A #101-53.

Science.gov (United States)

Arc, Arlington, TX.

This fact sheet uses a question-and-answer format to summarize what is known about phenylketonuria (PKU), an inherited metabolic disease that leads to mental retardation and other developmental disabilities if untreated in infancy. Questions and answers address the following topics: what PKU is; how PKU is inherited; the diagnosis of PKU; the…

Pathogenesis of cognitive dysfunction in phenylketonuria : Review of hypotheses

NARCIS (Netherlands)

de Groot, M. J.; Hoeksma, M.; Blau, N.; Reijngoud, D. J.; van Spronsen, F. J.

2010-01-01

In untreated phenylketonuria (PKU), deficiency of phenylalanine hydroxylase (PAH) results in elevated blood phenylalanine (Phe) concentrations and severe mental retardation. Current dietary treatment prevents mental retardation, but cognitive outcome remains suboptimal. The mechanisms by which

Cerebral biochemical abnormalities in experimental maternal phenylketonuria: gangliosides and sialoglycoproteins

International Nuclear Information System (INIS)

Loo, Y.H.; Hyde, K.R.; Lin, F.H.; Wisniewski, H.M.

1985-01-01

The present study sought a biochemical explanation for retarded brain development in the heterozygous offspring of the phenylketonuric (PKU) mother. Two rat models of simulated maternal PKU, one induced by p-chloropheylalanine and phenylalanine and the other by phenylacetate, were employed in this investigation. Maternal PKU had no influence on cerebral concentrations of DNA, protein, and cholesterol, which were normal in the 2 d old pup. However, there was a noticeable disruption of the normal ganglioside pattern and a significant reduction of sialoglycoproteins. Concomitant with a delayed drop in the gangliosides Q/sub 1b/ and D 3 , was a slower rise in M 1 and D/sub 1a/. At least 66% of sialoglycoproteins located on SDS-PAGE gel chromatograms, by radioactivity incorporated in vivo from radiolabeled N-acetylmannosamine and by ( 3 H) sialic acid released by neuraminidase from periodate-( 3 H) borohydride labeled glycoproteins, have mobilites of the cell adhesion molecules N-CAM and D-CAM. Whether the reduction of the sialogylcoproteins induced by maternal PKU is mainly in these cell adhesion molecules requires further investigation. Interference with the function of gangliosides and certain sialoglycoproteins during cerebral development may contribute to the brain dysfunction observed in the offspring of PKU mothers not on diet control during pregnancy. 49 references, 2 figures, 3 tables

Muscle-directed gene therapy for phenylketonuria (PKU): Development of transgenic mice with muscle-specific phenylalanine hydroxylase expression

Energy Technology Data Exchange (ETDEWEB)

Harding, C.O.; Messing, A.; Wolff, J.A. [Univ. of Wisconsin, Madison, WI (United States)

1994-09-01

Phenylketonuria (PKU) is an attractive target for gene therapy because of shortcomings in current therapy including lifelong commitment to a difficult and expensive diet, persistent mild cognitive deficits in some children despite adequate dietary therapy, and maternal PKU syndrome. Phenylalanine hydroxylase (PAH) is normally expressed only in liver, but we propose to treat PKU by introducing the gene for PAH into muscle. In order to evaluate both the safety and efficacy of this approach, we have a developed a trangenic mouse which expresses PAH in both cardiac and skeletal muscle. The transgene includes promoter and enhancer sequences from the mouse muscle creatine kinase (MCK) gene fused to the mouse liver PAH cDNA. Mice which have inherited the transgene are healthy, active, and do not exhibit any signs of muscle weakness or wasting. Ectopic PAH expression in muscle is not detrimental to the health, neurologic function, or reproduction of the mice. Pah{sup enu2} hyperphenylalaninemic mice, a model of human PAH deficiency, bred to carry the transgene have substantial PAH expression in cardiac and skeletal muscle but none in liver. Muscle PAH expression alone does not complement the hyperphenylalaninemic phenotype of Pah{sup enu2} mice. However, administration of reduced tetrahydrobiopterin to transgenic Pah{sup enu2} mice is associated with a 25% mean decrease in serum phenylalanine levels. We predict that ectopic expression of PAH in muscle along with adequate muscle supplies of reduced biopterin cofactor will decrease hyperphenylalaninemia in PKU.

[The mutation analysis of PAH gene and prenatal diagnosis in classical phenylketonuria family].

Science.gov (United States)

Yan, Yousheng; Hao, Shengju; Yao, Fengxia; Sun, Qingmei; Zheng, Lei; Zhang, Qinghua; Zhang, Chuan; Yang, Tao; Huang, Shangzhi

2014-12-01

To characterize the mutation spectrum of phenylalanine hydroxylase (PAH) gene and perform prenatal diagnosis for families with classical phenylketonuria. By stratified sequencing, mutations were detected in the exons and flaking introns of PAH gene of 44 families with classical phenylketonuria. 47 fetuses were diagnosed by combined sequencing with linkage analysis of three common short tandem repeats (STR) (PAH-STR, PAH-26 and PAH-32) in the PAH gene. Thirty-one types of mutations were identified. A total of 84 mutations were identified in 88 alleles (95.45%), in which the most common mutation have been R243Q (21.59%), EX6-96A>G (6.82%), IVS4-1G>A (5.86%) and IVS7+2T>A (5.86%). Most mutations were found in exons 3, 5, 6, 7, 11 and 12. The polymorphism information content (PIC) of these three STR markers was 0.71 (PAH-STR), 0.48 (PAH-26) and 0.40 (PAH-32), respectively. Prenatal diagnosis was performed successfully with the combined method in 47 fetuses of 44 classical phenylketonuria families. Among them, 11 (23.4%) were diagnosed as affected, 24 (51.1%) as carriers, and 12 (25.5%) as unaffected. Prenatal diagnosis can be achieved efficiently and accurately by stratified sequencing of PAH gene and linkage analysis of STR for classical phenylketonuria families.

Parkinsonism in phenylketonuria: a consequence of dopamine depletion?

NARCIS (Netherlands)

Velema, Marieke; Boot, Erik; Engelen, Marc; Hollak, Carla

2015-01-01

Phenylketonuria (PKU) is caused by a deficiency or inactivity of the enzyme phenylalanine hydroxylase that converts phenylalanine (Phe) to tyrosine (Tyr). It has been proposed that a reduction of brain Tyr levels, as well as reduced activity of the key regulatory enzyme of dopamine (DA) synthesis

Prefrontal dysfunction in early and continuously treated phenylketonuria

NARCIS (Netherlands)

Stemerdink, NBA; Kalverboer, AF; van der Meere, JJ; de Jong, LW; Slijper, FME; Verkerk, PH; van Spronsen, FJ

1999-01-01

In this study, we tested the hypothesis that patients with early and continuously treated phenylketonuria (PKU) are selectively impaired in cognitive functions dependent on the prefrontal cortex (PFC) over a wide age range. Thirty-six patients with PKU between 8 and 20 years of age and 36 controls

[Bone metabolism in adults with phenylketonuria - Hungarian data].

Science.gov (United States)

Barta, András Gellért; Sumánszki, Csaba; Reismann, Péter

2017-11-01

Patients with phenylketonuria have lower bone mineral density compared to healthy people, however, the ethiology of these alterations is not clear. Hungarian data were missing in this topic. The main aim of our study was to survey the correlation between metabolic control and change of bone mineral density in early treated Hungarian adult patients with phenylketonuria. In this monocentric study bone mineral density of 59 adult PKU patients have been repeatedly measured in a 4-year interval using dual-energy X-ray absorptiometry. Two subgroups have been established based on average blood phenylalanine levels. The correlation between the change in bone mineral density and average phenylalanine, tyrosine concentrations have been determined while initial bone mineral density and change have also been examined in the subgroups. Mean phenylalanine concentration was 614 (182-1222) micromol/L, whereas mean tyrosine concentration was 49 (24-99) micromol/L and the calculated ratio was 16 (4,5-35). Three patients have had severely decreased bone mineral density in either localisation while 22 have had mild decrease. Low bone mineral density compared to cronological age has been found by 9 patient. The mean change was +0.0380 (-0.1550-0.7800) g/cm 2 in femur, and +0.0120 (-0.57300-0.3130) g/cm 2 in the lumbar spine. There was a correlation in the change in Z-score neither with mean phenylalanine nor with tyrosine concentration. Bone mineral density was not changed and hardly influenced by the metabolic control in early-treated young adult phenylketonuria patients in a few years interval. Orv Hetil. 2017; 158(47): 1868-1872.

Protein substitute for children and adults with phenylketonuria.

Science.gov (United States)

Yi, Sarah H L; Singh, Rani H

2015-02-27

Phenylketonuria is an inherited metabolic disorder characterised by an absence or deficiency of the enzyme phenylalanine hydroxylase. The aim of treatment is to lower blood phenylalanine concentrations to the recommended therapeutic range to prevent developmental delay and support normal growth. Current treatment consists of a low-phenylalanine diet in combination with a protein substitute which is free from or low in phenylalanine. Guidance regarding the use, dosage, and distribution of dosage of the protein substitute over a 24-hour period is unclear, and there is variation in recommendations among treatment centres. This is an update of a Cochrane review first published in 2005, and previously updated in 2008. To assess the benefits and adverse effects of protein substitute, its dosage, and distribution of dose in children and adults with phenylketonuria who are adhering to a low-phenylalanine diet. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which consists of references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conference proceedings. We also contacted manufacturers of the phenylalanine-free and low-phenylalanine protein substitutes for any data from published and unpublished randomised controlled trials.Date of the most recent search of the Group's Inborn Errors of Metabolism Trials Register: 03 April 2014. All randomised or quasi-randomised controlled trials comparing: any dose of protein substitute with no protein substitute; an alternative dosage; or the same dose, but given as frequent small doses throughout the day compared with the same total daily dose given as larger boluses less frequently. Both authors independently extracted data and assessed trial quality. Three trials (69 participants) are included in this review. One trial investigated the use of protein substitute in 16 participants, while a further two trials investigated the

Phenylketonuria: central nervous system and microbiome interaction

Directory of Open Access Journals (Sweden)

Demian Arturo Herrera Morban

2017-06-01

Full Text Available Phenylketonuria (PKU is an autosomal recessive inborn error of metabolism characterized by increased phenylalanine (Phe levels causing an inadequate neurodevelopment; the treatment of PKU is a Phe-restricting diet, and as such it can modulate the intestinal microbiome of the individual, generating central nervous system secondary disturbances that, added to the baseline disturbance, can influence the outcome of the disease.

Congenital and Neurological Abnormalities in Infants with Phenylketonuria

Science.gov (United States)

Johnson, Charles F.; And Others

1978-01-01

Examined was the occurrence of congenital and neurological abnormalities in 150 children with phenylketonuria (PKU--a metabolic disorder which may result in mental retardation) age 1 year or older, who have been treated with a restricted phenylalanine diet, according to the protocol used in a nation-wide longitudinal collaborative study.…

Phenylketonuria in South Africa - A report on the status quo ...

African Journals Online (AJOL)

and treatment) of amino acidopathies, especially phenylketonuria (PKU), was conducted by the Department of National Health and Population Development. The motivation for this pilot programme was the high priority accorded PKU screening ...

Therapeutic brain modulation with targeted large neutral amino acid supplements in the Pah-enu2 phenylketonuria mouse model.

Science.gov (United States)

van Vliet, Danique; Bruinenberg, Vibeke M; Mazzola, Priscila N; van Faassen, Martijn Hjr; de Blaauw, Pim; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Kema, Ido P; Heiner-Fokkema, M Rebecca; van der Zee, Eddy A; van Spronsen, Francjan J

2016-11-01

Phenylketonuria treatment consists mainly of a Phe-restricted diet, which leads to suboptimal neurocognitive and psychosocial outcomes. Supplementation of large neutral amino acids (LNAAs) has been suggested as an alternative dietary treatment strategy to optimize neurocognitive outcome in phenylketonuria and has been shown to influence 3 brain pathobiochemical mechanisms in phenylketonuria, but its optimal composition has not been established. In order to provide additional pathobiochemical insight and develop optimal LNAA treatment, several targeted LNAA supplements were investigated with respect to all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria. Pah-enu2 (PKU) mice received 1 of 5 different LNAA-supplemented diets beginning at postnatal day 45. Control groups included phenylketonuria mice receiving an isonitrogenic and isocaloric high-protein diet or the AIN-93M diet, and wild-type mice receiving the AIN-93M diet. After 6 wk, brain and plasma amino acid profiles and brain monoaminergic neurotransmitter concentrations were measured. Brain Phe concentrations were most effectively reduced by supplementation of LNAAs, such as Leu and Ile, with a strong affinity for the LNAA transporter type 1. Brain non-Phe LNAAs could be restored on supplementation, but unbalanced LNAA supplementation further reduced brain concentrations of those LNAAs that were not (sufficiently) included in the LNAA supplement. To optimally ameliorate brain monoaminergic neurotransmitter concentrations, LNAA supplementation should include Tyr and Trp together with LNAAs that effectively reduce brain Phe concentrations. The requirement for Tyr supplementation is higher than it is for Trp, and the relative effect of brain Phe reduction is higher for serotonin than it is for dopamine and norepinephrine. The study shows that all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria can be targeted by specific LNAA supplements. The study thus

Long-chain polyunsaturated fatty acid status in children, adolescents and adults with phenylketonuria.

Science.gov (United States)

Gramer, Gwendolyn; Haege, Gisela; Langhans, Claus-Dieter; Schuhmann, Vera; Burgard, Peter; Hoffmann, Georg F

2016-06-01

Patients with phenylketonuria have been reported to be deficient in long-chain polyunsaturated fatty acids (LCPUFAs). It has been postulated that good compliance with the dietary regimen negatively influences LCPUFA status. In 36 patients with phenylketonuria and 18 age-matched healthy control subjects LCPUFA-levels in plasma phospholipids and cholesteryl esters, erythrocyte phosphatidylcholine and phosphatidylethanolamine were evaluated. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels did not differ significantly between patients and control subjects in plasma and erythrocyte fractions. There was a significant negative correlation between SDS (standard deviation) scores of DHA-levels in erythrocyte parameters from the respective age-matched control group and patients' concurrent and long-term phenylalanine levels for erythrocyte phosphatidylethanolamine and erythrocyte phosphatidylcholine. Patients with lower (higher) phenylalanine levels had positive (negative) DHA-SDS. In contrast to previous reports we did not find lower LCPUFA-levels in patients with phenylketonuria compared to age-matched healthy control subjects. Good dietary control was associated with better LCPUFA status. Copyright © 2016 Elsevier Ltd. All rights reserved.

First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

NARCIS (Netherlands)

Pratt, JJ; de Wolf, BTHM; Mantingh, A

Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down

77 FR 42768 - Leadership Meeting on Maternal, Fetal, and Infant Opioid Exposure and Neonatal Abstinence Syndrome

Science.gov (United States)

2012-07-20

... OFFICE OF NATIONAL DRUG CONTROL POLICY Leadership Meeting on Maternal, Fetal, and Infant Opioid Exposure and Neonatal Abstinence Syndrome AGENCY: Office of National Drug Control Policy. ACTION: Notice. SUMMARY: An ONDCP Leadership Meeting on Maternal, Fetal and Infant Opioid Exposure and Neonatal Abstinence...

Maternal support for autonomy: relationships with persistence for children with Down syndrome and typically developing children.

Science.gov (United States)

Gilmore, Linda; Cuskelly, Monica; Jobling, Anne; Hayes, Alan

2009-01-01

Maternal behaviors and child mastery behaviors were examined in 25 children with Down syndrome and 43 typically developing children matched for mental age (24-36 months). During a shared problem-solving task, there were no group differences in maternal directiveness or support for autonomy, and mothers in the two groups used similar verbal strategies when helping their child. There were also no group differences in child mastery behaviors, measured as persistence with two optimally challenging tasks. However, the two groups differed in the relationships of maternal style with child persistence. Children with Down syndrome whose mothers were more supportive of their autonomy in the shared task displayed greater persistence when working independently on a challenging puzzle, while children of highly directive mothers displayed lower levels of persistence. For typically developing children, persistence was unrelated to maternal style, suggesting that mother behaviors may have different causes or consequences in the two groups.

Simulation analysis of 9033 cases of second trimester maternal serum screening for Down’s syndrome

Directory of Open Access Journals (Sweden)

Shu-fang JIANG

2017-06-01

Full Text Available Objective To reduce the screening positive rate (SPR and improve clinical efficiency of maternal serum screening for Down's syndrome. Methods Nine thousand and thirty-three cases of second trimester maternal serum screening for Down's syndrome were included from Apr. 2013 to Apr. 2014 in the present study. The screening results, all basic data and equation curves were analyzed retrospectively. Based on the data from the authors' laboratory, the important adjustment parameters were simulated. Combined with postnatal follow-up results, the quality and clinical performance of second trimester serum screening for Down's syndrome were evaluated. Results The SPR of second trimester serum screening for Down's syndrome was 6.69%(604/9033, the detection rate (DR was 75%(3/4, and FPR was 6.65%(601/9033. The median multiple of median (MOM of alpha-fetoprotein (AFP was low and SPR was high, and MOM of free human chorionic gonadotropin β subunit (free hCGβ were high and SPR was high, while MOM of unconjugated estriol (uE3 were a little bit low, and SPR was slightly high. Considering these three factors, it is believed that the screening positive rate is high. By the simulation adjustments of MOM value equations (AFP and free hCGβ and weight correction equation, the SPR reduced to 4.11%(371/9033 after recalculating the risk, FPR declined to 4.07%(368/9033, and no more Down's syndrome fetus were missed compared with postnatal follow-up results. Conclusion Based on a localized setting depending on the local laboratory data, we suggest that the MOM value distributions(AFP, free hCGβ and uE3 and maternal weight should be regularly adjusted since it is a useful way to reduce the false-positive rate and improve clinical efficiency of maternal serum screening for Down's syndrome. DOI: 10.11855/j.issn.0577-7402.2017.04.13

PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION.

Science.gov (United States)

CENTERWALL, WILLARD R.; CENTERWALL, SIEGRIED A.

ADDRESSED TO PUBLIC HEALTH WORKERS AND PHYSICIANS IN GENERAL PRACTICE, THE PAMPHLET INTRODUCES METHODS OF DETECTING AND MANAGING PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION. INFORMATION, UPDATED FROM THE 1961 EDITION, IS INCLUDED ON THE INCIDENCE AND GENETICS, BIOCHEMISTRY, AND CLINICAL COURSE OF THE…

The challenges of managing coexistent disorders with phenylketonuria : 30 cases

NARCIS (Netherlands)

MacDonald, A.; Ahring, K.; Almeida, M. F.; Belanger-Quintana, A.; Blau, N.; Burlina, A.; Cleary, M.; Coskum, T.; Dokoupil, K.; Evans, S.; Feillet, F.; Gizewska, M.; Ozel, H. Gokmen; Lotz-Havla, A. S.; Kamienska, E.; Maillot, F.; Lammardo, A. M.; Muntau, A. C.; Puchwein-Schwepcke, A.; Robert, M.; Rocha, J. C.; Santra, S.; Skeath, R.; Straczek, K.; Trefz, F. K.; van Dam, E.; van Rijn, M.; van Spronsen, F.; Vijay, S.

2015-01-01

Introduction: The few published case reports of co-existent disease with phenylketonuria (PKU) are mainly genetic and familial conditions from consanguineous marriages. The clinical and demographic features of 30 subjects with PKU and co-existent conditions were described in this multi-centre,

Autism in Phenylketonuria Patients: From Clinical Presentation to Molecular Defects.

Science.gov (United States)

Khemir, Sameh; Halayem, Soumeyya; Azzouz, Hatem; Siala, Hajer; Ferchichi, Maherzia; Guedria, Asma; Bedoui, Amel; Abdelhak, Sonia; Messaoud, Taieb; Tebib, Neji; Belhaj, Ahlem; Kaabachi, Naziha

2016-06-01

Autism has been reported in untreated patients with phenylketonuria. The authors aimed to explore autism in 15 Tunisian and 4 Algerian phenylketonuria patients, and report their clinical, biochemical and molecular peculiarities. The Childhood Autism Rating Scale and the Autism Diagnostic Interview-Revised were used for the diagnosis of autism. Five exons of phenylalanine hydroxylase gene (7, 6, 10, 11, and 5) were amplified by polymerase chain reaction and directly sequenced. Among these patients, 15 were suffering from autism at the time of evaluation. Six mutations were identified: p.E280K, p.G352Vfs, IVS10nt11, p.I224T, p.R261Q, and p.R252W. There was no correlation between autism and mutations affecting the phenylalanine hydroxylase gene, but the age of diet onset was the determining factor in autistic symptoms' evolution. © The Author(s) 2016.

Dynamics of hyperphenylalaninemia and intellectual outcome in teenagers with phenylketonuria.

Science.gov (United States)

Didycz, Bożena; Bik-Multanowski, Mirosław

2017-01-01

Insufficient treatment adherence after early childhood is frequently observed in patients with phenylketonuria. Assessment of these individuals' long-term metabolic control could enable early detection of the risk of intellectual deterioration resulting from high blood phenylalanine concentration. However, the predictive value of specific parameters related to individual dynamics of hyperphenylalaninemia is not clear. Here, we assessed the impact of blood phenylalanine fluctuations during the first 12 years of life on cognitive outcome in early and continuously treated teenagers with phenylketonuria. We have analyzed a total of 5141 results of blood phenylalanine measurements in 32 patients. The phenylalanine levels of these patients were usually acceptable during their early childhood, but the control of hyperphenylalaninemia worsened and the average treatment adherence dropped to 40% during the late primary school. Our analysis revealed a strong association between the Wechsler intelligence verbal scores and the mean of the yearly means of phenylalanine concentrations (r=-0.62). The correlations of IQ scores with median phenylalanine concentrations and the variability of blood phenylalanine levels gave weaker associations. The Wechsler verbal scores were also strongly correlated with the treatment adherence level during preschool and late primary school (r=0.61 and 0.72). The mean of the yearly means of blood phenylalanine concentrations appears to be a better predictor of cognitive outcome in children with phenylketonuria than other parameters related to phenylalanine fluctuations. The percentage of acceptable phenylalanine levels below 50-60% should be regarded as a "red flag" due to the risk of intellectual deterioration in patients.

Maternal and paternal pragmatic speech directed to young children with Down syndrome and typical development.

Science.gov (United States)

de Falco, Simona; Venuti, Paola; Esposito, Gianluca; Bornstein, Marc H

2011-02-01

The aim of this study was to compare functional features of maternal and paternal speech directed to children with Down syndrome and developmental age-matched typically developing children. Altogether 88 parents (44 mothers and 44 fathers) and their 44 young children (22 children with Down syndrome and 22 typically developing children) participated. Parents' speech directed to children was obtained through observation of naturalistic parent-child dyadic interactions. Verbatim transcripts of maternal and paternal language were categorized in terms of the primary function of each speech unit. Parents (both mothers and fathers) of children with Down syndrome used more affect-salient speech compared to parents of typically developing children. Although parents used the same amounts of information-salient speech, parents of children with Down syndrome used more direct statements and asked fewer questions than did parents of typically developing children. Concerning parent gender, in both groups mothers used more language than fathers and specifically more descriptions. These findings held controlling for child age and MLU and family SES. This study highlights strengths and weaknesses of parental communication to children with Down syndrome and helps to identify areas of potential improvement through intervention. Copyright © 2010 Elsevier Inc. All rights reserved.

Maternal Support for Autonomy: Relationships with Persistence for Children with Down Syndrome and Typically Developing Children

Science.gov (United States)

Gilmore, Linda; Cuskelly, Monica; Jobling, Anne; Hayes, Alan

2009-01-01

Maternal behaviors and child mastery behaviors were examined in 25 children with Down syndrome and 43 typically developing children matched for mental age (24-36 months). During a shared problem-solving task, there were no group differences in maternal directiveness or support for autonomy, and mothers in the two groups used similar verbal…

Brief Communication: Maternal Plasma Autoantibodies Screening in Fetal Down Syndrome

Directory of Open Access Journals (Sweden)

Karol Charkiewicz

2016-01-01

Full Text Available Imbalance in the metabolites levels which can potentially be related to certain fetal chromosomal abnormalities can stimulate mother’s immune response to produce autoantibodies directed against proteins. The aim of the study was to determine the concentration of 9000 autoantibodies in maternal plasma to detect fetal Down syndrome. Method. We performed 190 amniocenteses and found 10 patients with confirmed fetal Down syndrome (15th–18th weeks of gestation. For the purpose of our control we chose 11 women without confirmed chromosomal aberration. To assess the expression of autoantibodies in the blood plasma, we used a protein microarray, which allows for simultaneous determination of 9000 proteins per sample. Results. We revealed 213 statistically significant autoantibodies, whose expression decreased or increased in the study group with fetal Down syndrome. The second step was to create a classifier of Down syndrome pregnancy, which includes 14 antibodies. The predictive value of the classifier (specificity and sensitivity is 100%, classification errors, 0%, cross-validation errors, 0%. Conclusion. Our findings suggest that the autoantibodies may play a role in the pathophysiology of Down syndrome pregnancy. Defining their potential as biochemical markers of Down syndrome pregnancy requires further investigation on larger group of patients.

Sleep disturbances in phenylketonuria : An explorative study in men and mice

NARCIS (Netherlands)

Bruinenberg, Vibeke M.; Gordijn, Marijke C. M.; MacDonald, Anita; van Spronsen, Francjan J.; Van der Zee, Eddy A.

2017-01-01

Sleep problems have not been directly reported in phenylketonuria (PKU). In PKU, the metabolic pathway of phenylalanine is disrupted, which, among others, causes deficits in the neurotransmitters and sleep modulators dopamine, norepinephrine, and serotonin. Understanding sleep problems in PKU

Late-Treated Phenylketonuria and Partial Reversibility of Intellectual Impairment

Science.gov (United States)

Grosse, Scott D.

2010-01-01

Individuals with late-treated phenylketonuria (PKU) not detected by newborn screening but who followed dietary treatment for at least 12 months before 7 years of age have intelligence quotient (IQ) scores that range from severe impairment to the low-normal range. Among adults with late-treated PKU in California, 85% of those who were born from…

Large daily fluctuations in plasma tyrosine in treated patients with phenylketonuria

NARCIS (Netherlands)

vanSpronsen, FJ; vanDijk, T; Smit, GPA; vanRijn, M; Reijngoud, DJ; Berger, Ruud; Heymans, HSA

1996-01-01

In patients with phenylketonuria (PKU), extra tyrosine supplementation is advocated in addition to tyrosine-enriched amino acid mixtures. PKU patients have low fasting plasma tyrosine concentrations, but little is known about tyrosine fluctuations during the day. Plasma tyrosine concentrations were

Maternal and obstetrical predictors of sudden infant death syndrome (SIDS).

Science.gov (United States)

Friedmann, Isabel; Dahdouh, Elias M; Kugler, Perlyne; Mimran, Gracia; Balayla, Jacques

2017-10-01

Public Health initiatives, such as the "Safe to Sleep" campaign, have traditionally targeted infants' risk factors for the prevention of Sudden Infant Death Syndrome (SIDS). However, controversy remains regarding maternal and obstetrical risk factors for SIDS. In our study, we sought out to determine both modifiable and non-modifiable obstetrical and maternal risk factors associated with SIDS. We conducted a population-based cohort study using the CDC's Linked Birth-Infant Death data from the United States for the year 2010. The impact of several obstetrical and maternal risk factors on the risk of overall infant mortality and SIDS was estimated using unconditional regression analysis, adjusting for relevant confounders. Our cohort consisted of 4,007,105 deliveries and 24,174 infant deaths during the first year of life, of which 1991 (8.2%) were due to SIDS. Prominent risk factors for SIDS included (OR [95% CI]): black race, 1.89 [1.68-2.13]; maternal smoking, 3.56 [3.18-3.99]; maternal chronic hypertension, 1.73 [1.21-2.48]; gestational hypertension, 1.51 [1.23-1.87]; premature birth <37 weeks, 2.16 [1.82-2.55]; IUGR, 2.46 [2.14-2.82]; and being a twin, 1.81 [1.43-2.29], p < 0.0001. Relative to a cohort of infants who died of other causes, risk factors with a predilection for SIDS were maternal smoking, 2.48 [2.16-2.83] and being a twin, 1.52 [1.21-1.91], p < 0.0001. Conclusions for practice: While certain socio-demographic and gestational characteristics are important risk factors, maternal smoking remains the strongest prenatal modifiable risk factor for SIDS. We recommend the continuation of Public Health initiatives that promote safe infant sleeping practices and smoking cessation during and after pregnancy.

Mapping the functional landscape of frequent phenylalanine hydroxylase (PAH) genotypes promotes personalised medicine in phenylketonuria.

Science.gov (United States)

Danecka, Marta K; Woidy, Mathias; Zschocke, Johannes; Feillet, François; Muntau, Ania C; Gersting, Søren W

2015-03-01

In phenylketonuria, genetic heterogeneity, frequent compound heterozygosity, and the lack of functional data for phenylalanine hydroxylase genotypes hamper reliable phenotype prediction and individualised treatment. A literature search revealed 690 different phenylalanine hydroxylase genotypes in 3066 phenylketonuria patients from Europe and the Middle East. We determined phenylalanine hydroxylase function of 30 frequent homozygous and compound heterozygous genotypes covering 55% of the study population, generated activity landscapes, and assessed the phenylalanine hydroxylase working range in the metabolic (phenylalanine) and therapeutic (tetrahydrobiopterin) space. Shared patterns in genotype-specific functional landscapes were linked to biochemical and pharmacological phenotypes, where (1) residual activity below 3.5% was associated with classical phenylketonuria unresponsive to pharmacological treatment; (2) lack of defined peak activity induced loss of response to tetrahydrobiopterin; (3) a higher cofactor need was linked to inconsistent clinical phenotypes and low rates of tetrahydrobiopterin response; and (4) residual activity above 5%, a defined peak of activity, and a normal cofactor need were associated with pharmacologically treatable mild phenotypes. In addition, we provide a web application for retrieving country-specific information on genotypes and genotype-specific phenylalanine hydroxylase function that warrants continuous extension, updates, and research on demand. The combination of genotype-specific functional analyses with biochemical, clinical, and therapeutic data of individual patients may serve as a powerful tool to enable phenotype prediction and to establish personalised medicine strategies for dietary regimens and pharmacological treatment in phenylketonuria. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Caring for children with phenylketonuria

Science.gov (United States)

Casey, Linda

2013-01-01

Abstract Objective To provide an overview of the diagnosis and management of phenylketonuria (PKU) in childhood with an emphasis on aspects relevant to family physicians providing ongoing care. Sources of information The author’s experience as the clinic physician in a regional pediatric PKU clinic is supplemented with references providing evidence for key points. Main message While metabolic clinics typically provide guidance regarding the specific management of PKU, the family doctor has an essential role in providing ongoing medical care. Conclusion Children and families have much to gain from strong relationships with family doctors, and family doctors can confidently provide care with awareness of the very few potential special needs of patients with PKU. PMID:23946023

Intellectual Assessment of 111 Four-Year-Old Children with Phenylketonuria

Science.gov (United States)

Dobson, James C.; And Others

1977-01-01

Available from: Arthur Retlaw and Associates, Inc., Suite 2080, 1603 Orrington Avenue, Evanston, Illinois 60201. A sample of 4-year-old children (n=111) with PKU (phenylketonuria) who were placed on dietary therapy between 3 and 92 days of age were assigned to two treatment groups based on "moderate" and "low" serum…

Speech and Language Skills in Children with Early Treated Phenylketonuria.

Science.gov (United States)

Ozanne, Anne E.; And Others

1990-01-01

The study of 29 children, age 7 months to 16 years, with early treated phenylketonuria found no significant differences on speech and/or language measures when compared with controls matched for age, sex, and socioeconomic level. Examination of individual scores, however, did reveal linguistic impairment in a small number of subjects. (Author/JDD)

Acute exercise in treated phenylketonuria patients: Physical activity and biochemical response

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Priscila Nicolao Mazzola

2015-12-01

Conclusions: Acute aerobic exercise followed by a Phe-restricted breakfast did not change Phe concentrations in treated phenylketonuria patients, but it was associated with decreased Phe/Tyr only in controls. Further studies are necessary to confirm our results in a higher number of patients.

Acute exercise in treated phenylketonuria patients : Physical activity and biochemical response

NARCIS (Netherlands)

Mazzola, Priscila Nicolao; Teixeira, Bruno Costa; Schirmbeck, Gabriel Henrique; Reischak-Oliveira, Alvaro; Derks, Terry G J; van Spronsen, Francjan J; Dutra-Filho, Carlos Severo; Schwartz, Ida Vanessa Doederlein

2015-01-01

BACKGROUND: In phenylketonuria, dietary treatment prevents most of the severe brain disease. However, patients have to follow a diet restricted in several natural components, what may cause decreased bone density and obesity. Exercise is known to improve both mental functioning and bone density also

Blood phenylalanine control in phenylketonuria : a survey of 10 European centres

NARCIS (Netherlands)

Ahring, K.; Belanger-Quintana, A.; Dokoupil, K.; Gokmen-Ozel, H.; Lammardo, A. M.; MacDonald, A.; Motzfeldt, K.; Nowacka, M.; van Rijn, M.; Robert, M.

Background: Only limited data are available on the blood phenylalanine (Phe) concentrations achieved in European patients with phenylketonuria (PKU) on a low-Phe diet. Objective: A survey was conducted to compare blood Phe control achieved in diet-treated patients with PKU of different age groups in

Linking genotypes database with locus-specific database and genotype-phenotype correlation in phenylketonuria.

Science.gov (United States)

Wettstein, Sarah; Underhaug, Jarl; Perez, Belen; Marsden, Brian D; Yue, Wyatt W; Martinez, Aurora; Blau, Nenad

2015-03-01

The wide range of metabolic phenotypes in phenylketonuria is due to a large number of variants causing variable impairment in phenylalanine hydroxylase function. A total of 834 phenylalanine hydroxylase gene variants from the locus-specific database PAHvdb and genotypes of 4181 phenylketonuria patients from the BIOPKU database were characterized using FoldX, SIFT Blink, Polyphen-2 and SNPs3D algorithms. Obtained data was correlated with residual enzyme activity, patients' phenotype and tetrahydrobiopterin responsiveness. A descriptive analysis of both databases was compiled and an interactive viewer in PAHvdb database was implemented for structure visualization of missense variants. We found a quantitative relationship between phenylalanine hydroxylase protein stability and enzyme activity (r(s) = 0.479), between protein stability and allelic phenotype (r(s) = -0.458), as well as between enzyme activity and allelic phenotype (r(s) = 0.799). Enzyme stability algorithms (FoldX and SNPs3D), allelic phenotype and enzyme activity were most powerful to predict patients' phenotype and tetrahydrobiopterin response. Phenotype prediction was most accurate in deleterious genotypes (≈ 100%), followed by homozygous (92.9%), hemizygous (94.8%), and compound heterozygous genotypes (77.9%), while tetrahydrobiopterin response was correctly predicted in 71.0% of all cases. To our knowledge this is the largest study using algorithms for the prediction of patients' phenotype and tetrahydrobiopterin responsiveness in phenylketonuria patients, using data from the locus-specific and genotypes database.

Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness.

Science.gov (United States)

Jeannesson-Thivisol, Elise; Feillet, François; Chéry, Céline; Perrin, Pascal; Battaglia-Hsu, Shyue-Fang; Herbeth, Bernard; Cano, Aline; Barth, Magalie; Fouilhoux, Alain; Mention, Karine; Labarthe, François; Arnoux, Jean-Baptiste; Maillot, François; Lenaerts, Catherine; Dumesnil, Cécile; Wagner, Kathy; Terral, Daniel; Broué, Pierre; de Parscau, Loïc; Gay, Claire; Kuster, Alice; Bédu, Antoine; Besson, Gérard; Lamireau, Delphine; Odent, Sylvie; Masurel, Alice; Guéant, Jean-Louis; Namour, Fares

2015-12-15

Mutations in Phenylalanine Hydroxylase (PAH) gene cause phenylketonuria. Sapropterin (BH4), the enzyme cofactor, is an important therapeutical strategy in phenylketonuria. However, PAH is a highly polymorphic gene and it is difficult to identify BH4-responsive genotypes. We seek here to improve prediction of BH4-responsiveness through comparison of genotypes, BH4-loading test, predictions of responsiveness according to the literature and types and locations of mutations. A total of 364 French patients among which, 9 % had mild hyperphenylalaninemia, 17.7 % mild phenylketonuria and 73.1 % classical phenylketonuria, benefited from a 24-hour BH4-loading test and had the PAH gene sequenced and analyzed by Multiplex Ligation Probe Amplification. Overall, 31.6 % of patients were BH4-responsive. The number of different mutations found was 127, including 26 new mutations. The mutations c.434A > T, c.500A > T, c.529G > C, c.1045 T > G and c.1196 T > C were newly classified as being BH4-responsive. We identified 261 genotypes, among which 46 were newly recognized as being BH4-responsive. Even though patients carry 2 responsive alleles, BH4-responsiveness cannot be predicted with certainty unless they present mild hyperphenylalaninemia. BH4-responsiveness cannot be predicted in patients carrying one responsive mutation only. In general, the milder the phenotype is, the stronger the BH4-response is. Almost exclusively missense mutations, particularly in exons 12, 11 and 8, are associated with BH4-responsiveness and any other type of mutation predicts a negative response. This study is the first of its kind, in a French population, to identify the phenotype associated with several combinations of PAH mutations. As others, it highlights the necessity of performing simultaneously BH4 loading test and molecular analysis in monitoring phenylketonuria patients.

MATERNAL HEMOLYSIS, ELEVATED LIVER-ENZYMES AND LOW PLATELETS SYNDROME - SPECIFIC PROBLEMS IN THE NEWBORN

NARCIS (Netherlands)

EELTINK, CM; VANLINGEN, RA; AARNOUDSE, JG; DERKS, JB; OKKEN, A

To evaluate the effects of maternal haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome on the fetus and neonate we retrospectively investigated the outcome of 87 pregnancies. All women showed thrombocytopenia, elevated liver enzymes and haemolysis. None of them died. Nine infants

Maternal and paternal pragmatic speech directed to young children with Down syndrome and typical development

OpenAIRE

de Falco, Simona; Venuti, Paola; Esposito, Gianluca; Bornstein, Marc H.

2011-01-01

The aim of this study was to compare functional features of maternal and paternal speech directed to children with Down syndrome and developmental age-matched typically developing children. Altogether 88 parents (44 mothers and 44 fathers) and their 44 young children (22 children with Down syndrome and 22 typically developing children) participated. Parents’ speech directed to children was obtained through observation of naturalistic parent–child dyadic interactions. Verbatim transcripts of m...

Key European guidelines for the diagnosis and management of patients with phenylketonuria

NARCIS (Netherlands)

Spronsen, F.J. van; Wegberg, A.M.J. van; Ahring, K.; Belanger-Quintana, A.; Blau, N.; Bosch, A.M.; Burlina, A.; Campistol, J.; Feillet, F.; Gizewska, M.; Huijbregts, S.C.J.; Kearney, S.; Leuzzi, V.; Maillot, F.; Muntau, A.C.; Trefz, F.K.; Rijn, M. van de; Walter, J.H.; Macdonald, A.

2017-01-01

We developed European guidelines to optimise phenylketonuria (PKU) care. To develop the guidelines, we did a literature search, critical appraisal, and evidence grading according to the Scottish Intercollegiate Guidelines Network method. We used the Delphi method when little or no evidence was

Key European guidelines for the diagnosis and management of patients with phenylketonuria

NARCIS (Netherlands)

van Spronsen, Francjan J.; van Wegberg, Annemiek M. J.; Ahring, Kirsten; Belanger-Quintana, Amaya; Blau, Nenad; Bosch, Annet M.; Burlina, Alberto; Campistol, Jaime; Feillet, Francois; Gizewska, Maria; Huijbregts, Stephan C.; Kearney, Shauna; Leuzzi, Vincenzo; Maillot, Francois; Muntau, Ania C.; Trefz, Fritz K.; van Rijn, Margreet; Walter, John H.; MacDonald, Anita

We developed European guidelines to optimise phenylketonuria (PKU) care. To develop the guidelines, we did a literature search, critical appraisal, and evidence grading according to the Scottish Intercollegiate Guidelines Network method. We used the Delphi method when little or no evidence was

Neurotransmitter positron emission tomographic-studies in adults with phenylketonuria, a pilot study

NARCIS (Netherlands)

Paans, AMJ; Pruim, J; Smit, GPA; Visser, G; Willemsen, ATM; Ullrich, K

Patients with phenylketonuria (PKU) may suffer from cognitive and neurological deficits which are related to reduced intracerebral concentrations of catecholamines. The function of phenylalanine (Phe) as an inhibitor of the uptake of the precursor amino acid tyrosine (Tyr) through the blood-brain

Dietary amino acid intakes associated with a low-phenylalanine diet combined with amino acid medical foods and glycomacropeptide medical foods and neuropsychological outcomes in subjects with phenylketonuria

Directory of Open Access Journals (Sweden)

Bridget M. Stroup

2017-08-01

Full Text Available This article provides original data on median dietary intake of 18 amino acids from amino acid medical foods, glycomacropeptide medical foods, and natural foods based on 3-day food records obtained from subjects with phenylketonuria who consumed low-phenylalanine diets in combination with amino acid medical foods and glycomacropeptide medical foods for 3 weeks each in a crossover design. The sample size of 30 subjects included 20 subjects with classical phenylketonuria and 10 with a milder or variant form of phenylketonuria. Results are presented for the Delis-Kaplan Executive Function System and the Cambridge Neuropsychological Test Automated Battery; the tests were administered at the end of each 3-week dietary treatment with amino acid medical foods and glycomacropeptide medical foods. The data are supplemental to our clinical trial, entitled “Glycomacropetide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial, 2016 (1 and “Metabolomic changes demonstrate reduced bioavailability of tyrosine and altered metabolism of tryptophan via the kynurenine pathway with ingestion of medical foods in phenylketonuria, 2017 (2. This data has been made public and has utility to clinicians and researchers due to the following: 1 This provides the first comprehensive report of typical intakes of 18 amino acids from natural foods, as well as amino acid and glycomacropeptide medical foods in adolescents and adults with phenylketonuria; and 2 This is the first evidence of similar standardized neuropsychological testing data in adolescents and adults with early-treated phenylketonuria who consumed amino acid and glycomacropeptide medical foods.

Bloom syndrome and maternal uniparental disomy for chromosome 15

Energy Technology Data Exchange (ETDEWEB)

Woodage, T.; Prasad, M.; Trent, R.J.; Smith, A. (Children' s Hospital, Camperdown, New South Wales (New Zealand)); Dixon, J.W.; Romain, D.R.; Columbano-Green, L.M.; Selby, R.E. (Wellington Hospital (New Zealand)); Graham, D. (Waikato Hospital, Hamilton (New Zealand)); Rogan, P.K. (Pennsylvania State Univ., Hershey, PA (United States)) (and others)

1994-07-01

Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions. 37 refs., 3 figs., 2 tabs.

Role of maternal gesture use in speech use by children with fragile X syndrome.

Science.gov (United States)

Hahn, Laura J; Zimmer, B Jean; Brady, Nancy C; Swinburne Romine, Rebecca E; Fleming, Kandace K

2014-05-01

The purpose of this study was to investigate how maternal gesture relates to speech production by children with fragile X syndrome (FXS). Participants were 27 young children with FXS (23 boys, 4 girls) and their mothers. Videotaped home observations were conducted between the ages of 25 and 37 months (toddler period) and again between the ages of 60 and 71 months (child period). The videos were later coded for types of maternal utterances and maternal gestures that preceded child speech productions. Children were also assessed with the Mullen Scales of Early Learning at both ages. Maternal gesture use in the toddler period was positively related to expressive language scores at both age periods and was related to receptive language scores in the child period. Maternal proximal pointing, in comparison to other gestures, evoked more speech responses from children during the mother-child interactions, particularly when combined with wh-questions. This study adds to the growing body of research on the importance of contextual variables, such as maternal gestures, in child language development. Parental gesture use may be an easily added ingredient to parent-focused early language intervention programs.

Reduced bone mineral density in Chinese children with phenylketonuria.

Science.gov (United States)

Wang, Kundi; Shen, Ming; Li, Honglei; Li, Xiaowen; He, Chun

2017-05-24

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder. Dietary control of classic PKU needs restriction of natural proteins. The diet results in unbalanced nutrition, which might affect the physical development of the patients. Our aim was to evaluate bone mineral density (BMD) in children with PKU. To investigate the BMD of children with PKU, 41 children with PKU and 64 healthy controls were recruited (all 3-4 years of age). Body weight and height, BMD, Phe blood levels, thyroid function, calcium, phosphorus, iron metabolism markers, and vitamin D3 were measured. Body height and BMD of patients were lower than in controls. The BMD of controls was positively associated with age, body weight and height. In patients, BMD was positively associated with body weight. There was no correlation between Phe blood levels and BMD in patients. Blood levels of alkaline phosphatase were higher in patients compared to controls. Blood calcium levels were higher in 4-year-old patients, while the body weight was lower compared to controls. Thyroid function, iron metabolism markers, vitamin D3 levels and IGF-1 levels were normal. Reduced BMD was observed in children with phenylketonuria, but the exact reasons for this remain to be elucidated.

Maternal Polycystic Ovary Syndrome and Risk for Attention-Deficit/Hyperactivity Disorder in the Offspring.

Science.gov (United States)

Kosidou, Kyriaki; Dalman, Christina; Widman, Linnea; Arver, Stefan; Lee, Brian K; Magnusson, Cecilia; Gardner, Renee M

2017-11-01

Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood neurodevelopmental disorder, and boys are two to three times more likely to develop ADHD. Maternal polycystic ovary syndrome (PCOS), a common metabolic disorder associated with excess circulating androgens, has been associated with increased risk for autism spectrum disorder in the offspring. In this study, we aimed to investigate whether maternal PCOS increases the risk for ADHD in the offspring. We conducted a matched case-control study using health and population data registers for all children born in Sweden from 1984 to 2008. Maternal PCOS was defined by ICD-coded register diagnosis. The outcome of ADHD was defined as an ICD-coded register diagnosis of ADHD and/or registered prescription of medications to treat ADHD. A total of 58,912 ADHD cases (68.8% male) were identified and matched to 499,998 unaffected controls by sex and birth month and year. Maternal PCOS increased the odds of offspring ADHD by 42% after adjustment for confounders (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.26-1.58). Exclusion of ADHD cases with comorbid autism spectrum disorder attenuated but did not explain the relationship (OR, 1.34; 95% CI, 1.18-1.52). The risk was somewhat elevated for ADHD with comorbid autism spectrum disorder (OR, 1.76; 95% CI, 1.37-2.26). The risk for ADHD was higher among obese mothers with PCOS (OR, 1.68; 95% CI, 1.31-2.17) and was highest among obese mothers with PCOS and other features of metabolic syndrome (OR, 2.59; 95% CI, 1.02-6.58). This study provides evidence that maternal PCOS may subtly influence the neurodevelopment of the offspring, resulting in increased risk for neurodevelopmental disorders such as ADHD. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Behaviour and school achievement in patients with early and continuously treated phenylketonuria

NARCIS (Netherlands)

Stemerdink, B.A.; Kalverboer, A.F.; Meere, J.J. van der; Molen, M.W. van der; Huisman, J.; Jong, L.W.A. de; Slijper, F.M.E.; Verkerk, P.H.; Spronsen, F.J. van

2000-01-01

Thirty patients with early and continuously treated phenylketonuria (PKU) between 8 and 20 years of age were compared with 30 controls, matched individually for age, sex, and educational level of both parents, on behaviour rating scales for parents and teachers as well as a school achievement scale.

Analog kefir production with a low phenylalanine for Phenylketonuria

OpenAIRE

Amir Yari; Yousef Ramezan

2017-01-01

Phenylketonuria (PKU) is one of the most prevalent types of hereditary metabolic disorders which is caused due to an absence or reduction of the activity of the Phenylalanine hydroxylase enzyme in the liver which in turn, inhibits the transformation of phenylalanine (Phe) to tyrosine. In clinical terms, this disorder is displayed with severe, permanent and irreversible mental retardation. This research was aimed at development of a highly nutrient and acceptable suitable analogue Kefir drink ...

Newborn Screening for Phenylketonuria

Directory of Open Access Journals (Sweden)

Gustavo J. C. Borrajo PhD

2016-12-01

Full Text Available Newborn screening (NBS for phenylketonuria in Latin America gave its first step in an organized way 3 decades ago when the first national NBS program was implemented in Cuba. From then onward, it experienced a slow but continuous growing, being currently possible to find from countries where no NBS activity is known to several countries with consolidated NBS programs. This complex scenario gave rise to a great diversity in the criteria used for sample collection, selection of analytical methods, and definition of cutoff values. Considering this context, a consensus meeting was held in order to unify such criteria, focusing the discussion in the following aspects—recommended blood specimens and sample collection time; influence of early discharge, fasting, parenteral nutrition, blood transfusions, extracorporeal life support, and antibiotics; main causes of transient hyperphenylalaninemias; required characteristics for methods used in phenylalanine measurement; and finally, criteria to define the more appropriate cutoff values.

PHENYLKETONURIA, DETECTION IN THE NEWBORN INFANT AS A ROUTINE HOSPITAL PROCEDURE.

Science.gov (United States)

GUTHRIE, ROBERT; WHITNEY, STEWART

A FIELD TRIAL OF AN INHIBITION ASSAY METHOD FOR SCREENING FOR PHENYLKETONURIA (PKU) TESTED MORE THAN 400,000 NEWBORN INFANTS PRIOR TO DISCHARGE FROM THE HOSPTIAL. IN ALL, 39 CASES WERE FOUND, A HIGHER INCIDENCE THAN HAD PREVIOUSLY BEEN EXPECTED. THE PRACTICALITY OF THE INHIBITION ASSAY METHOD WAS ALSO DEMONSTRATED. THE REPORT DETAILS THE TRIAL'S…

Maternal discipline of children with Asperger Syndrome and nonverbal learning disorders.

Science.gov (United States)

Little, Liza

2002-01-01

This study investigated how often mothers of children with Asperger Syndrome and nonverbal learning disorders reported using either psychological aggression (shouting, cursing, name calling) or corporal punishment (spanking, hitting) when disciplining their children, and also examined the correlates of these methods of discipline. A descriptive study of 41l mothers with children between ages 4 and 17 years. Mothers were recruited by placing an invitation on two national Web sites; one for parents of children with Asperger syndrome and one for parents of children with nonverbal learning disabilities. An anonymous, mailed survey was used and a 70% response rate was obtained. The Conflict Tactics Scale-Child Form was used to measure psychological aggression and corporal punishment. Univariate analyses were used to describe the child and maternal characteristics and maternal rates of discipline. The correlates of maternal discipline were measured using bivariate analyses. The overall reported use of any corporal punishment (slaps on the hand, arm, and leg; hitting on the buttocks with a belt or brush; spanking on the buttocks with a hand; pinching and shaking) during the past year was 58%. The yearly use of any psychological aggression (screaming and yelling, cursing, threatening to hit or spank, threatening to kick out or send away, calling the child "dumb" or "lazy") was 95%. Spanking declined with increasing age of the child and the mother. Mothers who used psychological aggression were more likely to use corporal punishment with their child. Informed nurses working with these populations can use the results of this study to help address the stresses felt by these mothers, and to teach alternative strategies of coping to mothers who are in danger of using psychological aggression and corporal punishment.

Metabolic syndrome in children and adolescents with phenylketonuria

Directory of Open Access Journals (Sweden)

Viviane C. Kanufre

2015-01-01

Conclusion: The results of this study suggest that patients with PKU and excess weight are potentially vulnerable to the development of metabolic syndrome. Therefore, it is necessary to conduct clinical and laboratory monitoring, aiming to prevent metabolic changes, as well as excessive weight gain and its consequences, particularly cardiovascular risk.

Phase 1 Trial of Subcutaneous rAvPAL-PEG in Subjects with Phenylketonuria

Science.gov (United States)

Longo, Nicola; Harding, Cary O.; Burton, Barbara K.; Grange, Dorothy K.; Vockley, Jerry; Wasserstein, Melissa; Rice, Gregory M.; Musson, Donald G.; Gu, Zhonghua; Sile, Saba

2014-01-01

Objective Phenylketonuria is an inherited disease caused by impaired activity of phenylalanine hydroxylase, the enzyme that converts phenylalanine to tyrosine, leading to accumulation of phenylalanine and subsequent neurocognitive dysfunction. A phenylalanine-restricted diet initiated early in life can ameliorate the toxic effects of phenylalanine. However, the diet is onerous and compliance is extremely difficult. Phenylalanine ammonia lyase (PAL) is a prokaryotic enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. This Phase 1, multicenter clinical trial evaluated the safety, tolerability, pharmacokinetics and efficacy of rAvPAL-PEG (recombinant Anabaena variabilis PAL produced in E. coli conjugated with polyethylene glycol [PEG] to reduce immunogenicity) in reducing phenylalanine levels in subjects with phenylketonuria. Methods Single subcutaneous injections of rAvPAL-PEG in escalating doses (0·001, 0·003, 0·01, 0·03, and 0·1 mg/kg) were administered to 25 adults with phenylketonuria recruited from those attending metabolic clinics in North America whose blood phenylalanine concentrations were ≥600 μmol/L. Results The most frequently reported adverse events were injection-site reactions and dizziness. Reactions were self-limited without sequelae. During the trial, two subjects had adverse reactions to intramuscular (IM) medroxyprogesterone acetate, a drug containing polyethylene glycol as an excipient. Three subjects developed a generalized skin rash at the highest rAvPAL-PEG dose (0·1 mg/kg). Drug levels peaked ∼5 days after the injection. Treatment was effective in reducing blood phenylalanine in all five subjects receiving the highest dose (0·1 mg/kg, mean percent change of -58 from baseline), with a nadir ∼6 days after injection and inverse correlation between drug and phenylalanine concentrations in plasma. Phenylalanine concentrations returned to near-baseline levels ∼20 days after the single injection. Conclusions

Therapeutic implication of L-phenylalanine aggregation mechanism and its modulation by D-phenylalanine in phenylketonuria

Science.gov (United States)

Singh, Virender; Rai, Ratan Kumar; Arora, Ashish; Sinha, Neeraj; Thakur, Ashwani Kumar

2014-01-01

Self-assembly of phenylalanine is linked to amyloid formation toxicity in phenylketonuria disease. We are demonstrating that L-phenylalanine self-assembles to amyloid fibrils at varying experimental conditions and transforms to a gel state at saturated concentration. Biophysical methods including nuclear magnetic resonance, resistance by alpha-phenylglycine to fibril formation and preference of protected phenylalanine to self-assemble show that this behaviour of L-phenylalanine is governed mainly by hydrophobic interactions. Interestingly, D-phenylalanine arrests the fibre formation by L-phenylalanine and gives rise to flakes. These flakes do not propagate further and prevent fibre formation by L-phenylalanine. This suggests the use of D-phenylalanine as modulator of L-phenylalanine amyloid formation and may qualify as a therapeutic molecule in phenylketonuria. PMID:24464217

Mutational spectrum of phenylketonuria in Jiangsu province.

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Chen, Ya-fen; Jia, Hai-tao; Chen, Zhong-hai; Song, Jia-ping; Liang, Yu; Pei, Jing-jing; Wu, Zhi-jun; Wang, Jing; Qiu, Ya-li; Liu, Gang; Sun, Dong-mei; Jiang, Xin-ye

2015-10-01

Phenylketonuria (PKU) is caused by variants in the phenylalanine hydroxylase (PAH) gene. We systematically investigated all 13 exons of the PAH gene and their flanking introns in 31 unrelated patients and their parents using next-generation sequencing (NGS). A total of 33 different variants were identified in 58 of 62 mutant PAH alleles. The prevalent variants with a relative frequency of 5 % or more were c.721C > T, c.1068C > A, c.611A > G, c.1197A > T, c.728G > A, c.331C > T, and c.442-1G > A. One novel variant was identified in this study-c.699C > G. We studied genotype-phenotype correlations using the Guldberg arbitrary value (AV) system, which revealed a consistency rate of 38 % (8/21) among the 21 predicted phenotypes. The genotype-based prediction of BH4 responsiveness was also evaluated, and 14 patients (45.2 %) were predicted to be BH4 responsive. This study presents the spectrum of PAH variants in Jiangsu province. The information obtained from the genotype-based prediction of BH4 responsiveness might be used for the rational selection of candidates for BH4 testing. • Phenylketonuria (PKU) is caused by variants in the phenylalanine hydroxylase (PAH) gene. • The spectrum of PAH variants in different Chinese populations has been reported. What is new: • This is the first report on the spectrum of PAH variants in Jiangsu province. • This study identified one novel PAH variant-c.699C>G-and and tries to show a genotype-phenotype relationship also regarding BH4-responsiveness.

INCREASED MATERNAL SERUM ALPHA-FETOPROTEIN AND HUMAN CHORIONIC-GONADOTROPIN IN COMPROMISED PREGNANCIES OTHER THAN FOR NEURAL-TUBE DEFECTS OR DOWN-SYNDROME

NARCIS (Netherlands)

BEEKHUIS, [No Value; VANLITH, JMM; DEWOLF, BTHM; MANTINGH, A

Intrauterine fetal death occurred in four women who were 'screen-positive' in a screening programme for neural tube defects (NTDs) and Down syndrome (DS). These women had very high levels of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG). Therefore,

Fenilcetonúria no Brasil: evolução e casos Phenylketonuria in Brazil: evolution and cases

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Lenice Teresinha Bussolotto Monteiro

2006-06-01

Full Text Available Os objetivos deste trabalho foram: agrupar informações relevantes à fenilcetonúria, destacando causa, sintomas, tratamento dietético, prevalência nacional e internacional; e identificar a situação do Brasil quanto a essa disfunção metabólica. Foi realizado um levantamento de dados junto ao Ministério da Saúde e aos vários centros de tratamento para fenilcetonúricos no Brasil. Neste estudo foram localizados 1.225 casos de portadores da doença, que recebiam controle e assistência. Um dos principais problemas detectados foi que, na maioria das regiões brasileiras, portadores de fenilcetonúria precisam deslocar-se de seus estados, procurando centros mais capacitados para o tratamento. Nas regiões Norte e Nordeste são poucas as informações disponíveis. Com os resultados obtidos conclui-se que, nem a triagem neonatal, nem os centros de tratamento para fenilcetonúria cobrem todos os casos brasileiros. O Brasil está avançando na organização de dados e ações relativas à fenilcetonúria. Os alimentos específicos são restritos e de alto custo. Novas opções estão sendo pesquisadas, porém, há muito para ser feito, principalmente em pesquisa e produção de alimentos.The objectives of this work were to gather relevant information on phenylketonuria, highlighting the cause, symptoms, dietary treatment, national and international prevalence and to identify the situation of this metabolic disorder in Brazil. Data were obtained from the National Ministry of Health and phenylketonuria treatment units in Brazil. In this study, 1225 people who received control and assistance for the disease were included. One of the main problems detected was that in most of Brazil, phenylketonuria patients have to leave their home state seeking more qualified treatment centers. In the Northern and Northeastern Regions, little information is available. The results obtained lead to the conclusion that neither newborn screening, nor

Neonatal withdrawal syndrome after chronic maternal consumption of 4-methylethcathinone.

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Pichini, Simona; Rotolo, Maria Concetta; García, Jordi; Girona, Noelia; Leal, Lorna; García-Algar, Oscar; Pacifici, Roberta

2014-12-01

Synthetic cathinones have been markedly present in the Spanish drug market in recent years. These substances can be easily obtained in "smart shops", smoke shops, gas stations and web sites where they can be bought and received anonymously avoiding normal law controls. For the first time we present a case of a neonatal withdrawal syndrome in a baby born to a woman who was a chronic consumer of 4-methylethcathinone. The newborn presented with increased jitteriness and irritability, highpitched cry, hypertonia in the limbs and brisk tendon reflexes. 4-Methylethcathinone was identified and quantified by liquid chromatography tandem mass spectrometry in the four subsequent 3cm segments of maternal hair (4.3, 4.0, 4.0 and 3.9ng/mg hair starting from most proximal segment) accounting for maternal consumption during the whole pregnancy and before and in neonatal meconium (0.7ng/g) confirming fetal exposure during intrauterine life. Methadone and its metabolite were also measured in maternal and neonatal matrices. Counseling pregnant women and women who may become pregnant on the consequences of fetal drug exposure to new designer drugs like 4-methylethcathinone is critical to preventing poor neonatal outcomes. This case report is informative to those studying designer drugs and those clinically involved with pregnant women abusing psychoactive substances. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Indicator Amino Acid Oxidation Method with the Use of l-[1-13C]Leucine Suggests a Higher than Currently Recommended Protein Requirement in Children with Phenylketonuria.

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Turki, Abrar; Ueda, Keiko; Cheng, Barbara; Giezen, Alette; Salvarinova, Ramona; Stockler-Ipsiroglu, Sylvia; Elango, Rajavel

2017-02-01

Phenylketonuria is characterized by mutations in the Phe hydroxylase gene that leads to the accumulation of Phe in plasma and the brain. The standard of care for phenylketonuria is nutritional management with dietary restriction of Phe and the provision of sufficient protein and energy for growth and health maintenance. The protein requirement in children with phenylketonuria is empirically determined based upon phenylketonuria nutritional guidelines that are adjusted individually in response to biochemical markers and growth. We determined dietary protein requirements in children with phenylketonuria with the use of the indicator amino acid oxidation (IAAO) technique, with l-[1- 13 C]Leu as the indicator amino acid. Four children (2 males; 2 females) aged 9-18 y with phenylketonuria [mild hyperphenylalanemia (mHPA); 6-10 mg/dL (360-600 μmol/L)] were recruited to participate in ≥7 separate test protein intakes (range: 0.2-3.2 g ⋅ kg -1 ⋅ d -1 ) with the IAAO protocol with the use of l-[1- 13 C]Leu followed by the collection of breath and urine samples over 8 h. The diets were isocaloric and provided energy at 1.7 times the resting energy expenditure. Protein was provided as a crystalline amino acid mixture based on an egg protein pattern, except Phe and Leu, which were maintained at a constant across intakes. Protein requirement was determined with the use of a 2-phase linear-regression crossover analysis of the rate of l-[1- 13 C]Leu tracer oxidation. The mean protein requirement was determined to be 1.85 g ⋅ kg -1 ⋅ d -1 (R 2 = 0.66; 95% CI: 1.37, 2.33). This result is substantially higher than the 2014 phenylketonuria recommendations (1.14-1.33 g ⋅ kg -1 ⋅ d -1 ; based on 120-140% above the current RDA for age). To our knowledge, this is the first study to directly define a quantitative requirement for protein intake in children with mHPA and indicates that current protein recommendations in children with phenylketonuria may be insufficient. This

Doxycycline hinders phenylalanine fibril assemblies revealing a potential novel therapeutic approach in phenylketonuria.

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De Luigi, Ada; Mariani, Alessandro; De Paola, Massimiliano; Re Depaolini, Andrea; Colombo, Laura; Russo, Luca; Rondelli, Valeria; Brocca, Paola; Adler-Abramovich, Lihi; Gazit, Ehud; Del Favero, Elena; Cantù, Laura; Salmona, Mario

2015-10-29

A new paradigm for the aetiopathology of phenylketonuria suggests the presence of amyloid-like assemblies in the brains of transgenic mouse models and patients with phenylketonuria, possibly shedding light on the selective cognitive deficit associated with this disease. Paralleling the amyloidogenic route that identifies different stages of peptide aggregation, corresponding to different levels of toxicity, we experimentally address for the first time, the physico-chemical properties of phenylalanine aggregates via Small Angle, Wide Angle X-ray Scattering and Atomic Force Microscopy. Results are consistent with the presence of well-structured, aligned fibres generated by milliMolar concentrations of phenylalanine. Moreover, the amyloid-modulating doxycycline agent affects the local structure of phenylalanine aggregates, preventing the formation of well-ordered crystalline structures. Phenylalanine assemblies prove toxic in vitro to immortalized cell lines and primary neuronal cells. Furthermore, these assemblies also cause dendritic sprouting alterations and synaptic protein impairment in neurons. Doxycycline counteracts these toxic effects, suggesting an approach for the development of future innovative non-dietary preventive therapies.

Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism.

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Tufekcioglu, Zeynep; Cakar, Arman; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat

2016-06-01

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 μmol/L, normal 39-240 μmol/L) with normal tyrosine level (61.20 μmol/L, normal 35-100 μmol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging.

Maladaptive Behavior Differences in Prader-Willi Syndrome Due to Paternal Deletion versus Maternal Uniparental Disomy.

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Dykens, Elisabeth M.; King, Bryan H.; Cassidy, Suzanne B.

1999-01-01

This study compared maladaptive behavior in 23 people with Prader-Willi syndrome due to paternal deletion and in 23 age- and gender-matched subjects with maternal uniparental disomy. Controlling for IQs, the deletion cases showed significantly higher maladaptive ratings, more symptom-related distress, and more behavior problems. Findings suggest a…

Prenatal management and perinatal outcome in giant placental chorioangioma complicated with hydrops fetalis, fetal anemia and maternal mirror syndrome

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García-Díaz Lutgardo

2012-07-01

Full Text Available Abstract Background Giant placental chorioangiomas have been associated with a number of severe fetal complications and high perinatal mortality. Case presentation We report a case of giant chorioangioma with fetal hydrops, additionally complicated by severe anemia, mild cardiomegaly with hyperdinamic heart circulation and maternal mirror syndrome. Intrauterine blood transfusion and amniodrainage was performed at 29 weeks. Worsening of the fetal and maternal condition prompted us to proceed with delivery at 29 + 5 weeks. The newborn died 3 hours later due to pulmonary hypoplasia and hemodynamic failure. Maternal course was favourable, mirror syndrome resolved in the second day and the patient was discharged four days following delivery. Conclusions In the case described here, fetal condition got worse despite of the anemia correction and amniodrainage. Our outcome raises the issue whether additional intrauterine clinical intervention, as intersticial laser, should have been performed to stop further deterioration of the fetal condition when progressive severe hydrops develops.

A pilot study: pain, fatigue and stress in maternal relatives of adolescent female psychiatric inpatients assessed for juvenile primary fibromyalgia syndrome.

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Lommel, Karen; Bamford, Jaime; Jhavari, Malhar; Martin, Catherine; Crofford, Leslie

2011-01-01

This study was designed to assess the presence of pain and impaired functioning in the maternal relatives of adolescent females in an inpatient adolescent psychiatric population. We compared the relatives of adolescents who met the criteria for juvenile primary fibromyalgia syndrome (JPFS) to relatives of adolescents who did not meet the criteria for JPFS. A total of 55 biological maternal relatives of adolescent females admitted to a psychiatric unit were recruited to participate in the study. Participants completed four self-administered questionnaires: Multidimensional Fatigue Inventory, Fibromyalgia Impact Questionnaire, Medical Outcomes Survey (SF36v2), and the EPIFUND Health Survey. The maternal relatives of adolescents who met the criteria for JPFS did not score higher than the maternal relatives of adolescents who did not meet the criteria for JPFS. However, all maternal relatives consistently scored higher on self-reported measures of pain, impaired functioning, fatigue, and fibromyalgia symptoms than the average patient diagnosed with fibromyalgia or a chronic pain syndrome. Mood disorders and pain disorders share genetic risk factors and vulnerability. Future research is needed to further delineate other factors impacting the maternal caregivers' functioning. These could include stress associated with an adolescent child with psychiatric issues severe enough to warrant hospitalization.

Adjusting diet with sapropterin in phenylketonuria

DEFF Research Database (Denmark)

MacDonald, Anita; Ahring, Kirsten; Dokoupil, Katharina

2011-01-01

others are able to relax the diet to some extent. Care is required when altering the phenylalanine-restricted diet, as this may have unintended nutritional consequences and must be undertaken with caution. New clinical protocols are required for managing any dietary change while maintaining control......The usual treatment for phenylketonuria (PKU) is a phenylalanine-restricted diet. Following this diet is challenging, and long-term adherence (and hence metabolic control) is commonly poor. Patients with PKU (usually, but not exclusively, with a relatively mild form of the disorder) who...... and new questions in the dietary management of these patients. Initially, patients and carers must understand clearly the likely benefits (and limitations) of sapropterin therapy. A minority of patients who respond to sapropterin are able to discontinue the phenylalanine-restricted diet completely, while...

Mosaic maternal uniparental disomy of chromosome 15 in Prader-Willi syndrome: utility of genome-wide SNP array.

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Izumi, Kosuke; Santani, Avni B; Deardorff, Matthew A; Feret, Holly A; Tischler, Tanya; Thiel, Brian D; Mulchandani, Surabhi; Stolle, Catherine A; Spinner, Nancy B; Zackai, Elaine H; Conlin, Laura K

2013-01-01

Prader-Willi syndrome is caused by the loss of paternal gene expression on 15q11.2-q13.2, and one of the mechanisms resulting in Prader-Willi syndrome phenotype is maternal uniparental disomy of chromosome 15. Various mechanisms including trisomy rescue, monosomy rescue, and post fertilization errors can lead to uniparental disomy, and its mechanism can be inferred from the pattern of uniparental hetero and isodisomy. Detection of a mosaic cell line provides a unique opportunity to understand the mechanism of uniparental disomy; however, mosaic uniparental disomy is a rare finding in patients with Prader-Willi syndrome. We report on two infants with Prader-Willi syndrome caused by mosaic maternal uniparental disomy 15. Patient 1 has mosaic uniparental isodisomy of the entire chromosome 15, and Patient 2 has mosaic uniparental mixed iso/heterodisomy 15. Genome-wide single-nucleotide polymorphism array was able to demonstrate the presence of chromosomally normal cell line in the Patient 1 and trisomic cell line in Patient 2, and provide the evidence that post-fertilization error and trisomy rescue as a mechanism of uniparental disomy in each case, respectively. Given its ability of detecting small percent mosaicism as well as its capability of identifying the loss of heterozygosity of chromosomal regions, genome-wide single-nucleotide polymorphism array should be utilized as an adjunct to the standard methylation analysis in the evaluation of Prader-Willi syndrome. Copyright © 2012 Wiley Periodicals, Inc.

Surfactant therapy for maternal blood aspiration: an unusual cause of neonatal respiratory distress syndrome.

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Celik, Istemi Han; Demirel, Gamze; Canpolat, Fuat Emre; Erdeve, Omer; Dilmen, Ugur

2012-10-01

Surfactant replacement therapy is the main treatment of neonatal respiratory distress syndrome. However, surfactant therapy has been shown to be effective in the treatment of other diseases causing neonatal respiratory diseases such as pulmonary hemorrhage, meconium aspiration syndrome, pneumonia/sepsis, pulmonary edema or acute lung injury resulting a secondary surfactant deficiency (SSD). Rarely, as like as in the present patient, exogenous blood aspiration such as breast milk or formula aspiration may lead to SSD. Blood in alveolus leads to a significant biochemical and functional disturbance of the surfactant system and inhibits surfactant production. Here, the authors report a preterm infant of 33 wk gestational age with secondary surfactant deficiency due to maternal blood aspiration because of abruptio placentae. She was received two courses of beractant, a natural bovine surfactant, therapy in 24 h. She was extubated on second day and did not require oxygen on 4(th) day. To the authors' knowledge, this is the first reported case of SSD due to maternal blood aspiration treated with surfactant. In conditions such as abruptio placentae, infant should be protected from blood aspiration and if respiratory distress occurs, surfactant inhibition and need for surfactant administration should be considered.

Up to date knowledge on different treatment strategies for phenylketonuria

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Bélanger-Quintana, Amaya; Burlina, Alberto; Harding, Cary O.; Muntau, Ania C.

2015-01-01

Dietary management for phenylketonuria was established over half a century ago, and has rendered an immense success in the prevention of the severe mental retardation associated with the accumulation of phenylalanine. However, the strict low-phenylalanine diet has several shortcomings, not the least of which is the burden it imposes on the patients and their families consequently frequent dietary non-compliance. Imperfect neurological outcome of patients in comparison to non-PKU individuals and nutritional deficiencies associated to the PKU diet are other important reasons to seek alternative therapies. In the last decade there has been an impressive effort in the investigation of other ways to treat PKU that might improve the outcome and quality of life of these patients. These studies have lead to the commercialization of sapropterin dihydrochloride, but there are still many questions regarding which patients to challenge with sapropterin what is the best challenge protocol and what could be the implications of this treatment in the long-term. Current human trials of PEGylated phenylalanine ammonia lyase are underway, which might render an alternative to diet for those patients non-responsive to sapropterin dihydrochloride. Preclinical investigation of gene and cell therapies for PKU is ongoing. In this manuscript, we will review the current knowledge on novel pharmacologic approaches to the treatment of phenylketonuria. PMID:21967857

Education of Students with Phenylketonuria (PKU): Information for Teachers, Administrators and Other School Personnel.

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National Inst. of Child Health and Human Development (NIH), Bethesda, MD.

This booklet summarizes current knowledge about phenylketonuria (PKU), an inherited condition that results in severe mental retardation if untreated, and discusses the psychoeducational implications of the condition. The introduction stresses the importance of early diagnosis (during the first days of life) and the effectiveness of a diet that…

Prevalence of Fetal Alcohol Syndrome and Maternal Characteristics in a Sample of Schoolchildren from a Rural Province of Croatia

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Ingeborg Barišić

2013-04-01

Full Text Available Fetal alcohol syndrome (FAS is a congenital syndrome caused by maternal alcohol consumption during pregnancy and is entirely preventable by abstinence from alcohol drinking during this time. Little is known about the prevalence of FAS and maternal alcohol consumption during pregnancy in Western countries. We present the results of FAS/partial fetal alcohol syndrome (PFAS prevalence study and maternal characteristics in a sample of schoolchildren from a rural province of Croatia. This study involved seven elementary schools with 1,110 enrolled children attending 1st to 4th grade and their mothers. We used an active case ascertainment method with passive parental consent and Clarified IOM criteria. The investigation protocol involved maternal data collection and clinical examination of children. Out of 1,110 mothers, 917 (82.6% answered the questionnaire. Alcohol exposure during pregnancy was admitted by 11.5%, regular drinking by 4.0% and binge drinking by 1.4% of questioned mothers. Clinical examination involved 824 (74.2% schoolchildren and disclosed 14 (1.7% with clinical signs of FAS and 41 (5.0% of PFAS. The observed FAS prevalence, based on 74.2% participation rate, was 16.9, PFAS 49.7 and combined prevalence was 66.7/1,000 examined schoolchildren. This is the first FAS prevalence study based on active ascertainment among schoolchildren and pregnancy alcohol drinking analysis performed in a rural community of Croatia and Europe. High prevalence of FAS/PFAS and pregnancy alcohol consumption observed in this study revealed that FAS is serious health problem in rural regions as well as a need to develop future studies and preventive measures for pregnancy alcohol drinking and FASD.

Prevalence of Fetal Alcohol Syndrome and Maternal Characteristics in a Sample of Schoolchildren from a Rural Province of Croatia

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Petković, Giorgie; Barišić, Ingeborg

2013-01-01

Fetal alcohol syndrome (FAS) is a congenital syndrome caused by maternal alcohol consumption during pregnancy and is entirely preventable by abstinence from alcohol drinking during this time. Little is known about the prevalence of FAS and maternal alcohol consumption during pregnancy in Western countries. We present the results of FAS/partial fetal alcohol syndrome (PFAS) prevalence study and maternal characteristics in a sample of schoolchildren from a rural province of Croatia. This study involved seven elementary schools with 1,110 enrolled children attending 1st to 4th grade and their mothers. We used an active case ascertainment method with passive parental consent and Clarified IOM criteria. The investigation protocol involved maternal data collection and clinical examination of children. Out of 1,110 mothers, 917 (82.6%) answered the questionnaire. Alcohol exposure during pregnancy was admitted by 11.5%, regular drinking by 4.0% and binge drinking by 1.4% of questioned mothers. Clinical examination involved 824 (74.2%) schoolchildren and disclosed 14 (1.7%) with clinical signs of FAS and 41 (5.0%) of PFAS. The observed FAS prevalence, based on 74.2% participation rate, was 16.9, PFAS 49.7 and combined prevalence was 66.7/1,000 examined schoolchildren. This is the first FAS prevalence study based on active ascertainment among schoolchildren and pregnancy alcohol drinking analysis performed in a rural community of Croatia and Europe. High prevalence of FAS/PFAS and pregnancy alcohol consumption observed in this study revealed that FAS is serious health problem in rural regions as well as a need to develop future studies and preventive measures for pregnancy alcohol drinking and FASD. PMID:23591786

Histopathological effects on the eye development during perinatal growth of albino rats maternally treated with experimental phenylketonuria during pregnancy

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Hany A. Hefty

2016-04-01

Full Text Available Phenylketonuria (PKU is a genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. The disease results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine to tyrosine. Although, this inborn error of metabolism was among the first in humans to be understood biochemically and genetically, little is known about the mechanisms involved in the pathology of PKU during neonatal brain development. Elevated concentrations of plasma phenylalanine were induced in pregnant rats by oral administration of 50mg/100g body weight alpha-methylphenylalanine plus phenylalanine supplementation at a dosage of 60mg/100g body weight two times daily after 6th day of onset of gestation till 14 & 16 days prenatal as well as at parturition. Treatment with alpha-methylphenylalanine resulted in significant reduction of retinal cell layers of prenatal fetuses and delivered newborns.   Histological abnormalities were detected manifested by either hyaline degeneration of lens structure or inducing lens cataract as well as comparative atrophy of retina associated with the development of malignant polypoid mass in the ganglionic cell layers in contact with the lens.

Maternal burn-out: an exploratory study.

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Séjourné, N; Sanchez-Rodriguez, R; Leboullenger, A; Callahan, S

2018-02-21

Maternal burn-out is a psychological, emotional and physiological condition resulting from the accumulation of various stressors characterised by a moderate but also a chronic and repetitive dimension. Little research has focused on this syndrome. The current study aims to assess maternal burn-out rate and to identify factors associated with this state of exhaustion. 263 French mothers aged between 20 and 49 years answered five scales quantifying maternal burn-out, perceived social support, parental stress, depression and anxiety symptoms and history of postnatal depression. About 20% of mothers were affected by maternal burn-out. The main factors related to maternal burn-out were having a child perceived as difficult, history of postnatal depression, anxiety, satisfaction of a balance between professional and personal life and parental stress. This research shows the need for further work on maternal burn-out to better understand and prevent this syndrome.

Phenylketonuria in The Netherlands : 93% of the mutations are detected by single-strand conformation analysis

NARCIS (Netherlands)

vanderSijsBos, CJM; Diepstraten, CM; Juyn, JA; Plaisier, M; Giltay, JC; vanSpronsen, FJ; Smit, GPA; Berger, R; Smeitink, JAM; PollThe, BT; vanAmstel, JKP

1996-01-01

Single-strand conformational analysis was used to screen for genetic defects in all thirteen exons of the phenylalanine hydroxylase gene (PAH) in phenylketonuria and hyperphenylalaninemia patients in the Netherlands. Exons that showed a bandshift were sequenced directly, In this way, we were able to

Randomized controlled trial of a protein substitute with prolonged release on the protein status of children with phenylketonuria.

Science.gov (United States)

Giovannini, Marcello; Riva, Enrica; Salvatici, Elisabetta; Cefalo, Graziella; Radaelli, Giovanni

2014-01-01

To examine whether a phenylalanine-free protein substitute with prolonged release may be beneficial to the protein status of children with phenylketonuria (PKU) compared to conventional substitutes. Sixty children with PKU, 7 to 16 years of age, were randomly allocated to receive either a prolonged-release (test) or the current conventional protein substitute for 30 days. Subjects were additionally sex and age matched with 60 subjects with mild hyperphenylalaninemia and 60 unaffected subjects. The protein status in children with PKU was assessed by albumin, transthyretin, and retinol-binding protein (RBP), and changes throughout the trial period were the primary outcome measures. Children with PKU did not differ in anthropometry from children with mild hyperphenylalaninemia or unaffected children but they ingested lower amounts of proteins (p phenylketonuria.

Social-cognitive functioning and social skills in patients with early treated phenylketonuria : a PKU-COBESO study

NARCIS (Netherlands)

Jahja, Rianne; van Spronsen, Francinus; de Sonneville, Leonardus; van der Meere, Jacob; Huijbregts, S; Bosch, Annet M.; Hollak, Carla E. M.; Rubio-Gozalbo, M. Estela; Brouwers, Martijn C. G. J.; Hofstede, Floris C.; de Vries, Maaike C.; Janssen, Mirian C. H.; van der Ploeg, Ans T.; Langendonk, Janneke G.

OBJECTIVE: Early treatment of phenylketonuria (ET-PKU) prevents mental retardation, but many patients still show cognitive and mood problems. In this study, it was investigated whether ET-PKU-patients have specific phenylalanine (Phe-)related problems with respect to social-cognitive functioning and

Social-cognitive functioning and social skills in patients with early treated phenylketonuria: a PKU-COBESO study

NARCIS (Netherlands)

Jahja, Rianne; van Spronsen, Francjan J.; de Sonneville, Leo M. J.; van der Meere, Jaap J.; Bosch, Annet M.; Hollak, Carla E. M.; Rubio-Gozalbo, M. Estela; Brouwers, Martijn C. G. J.; Hofstede, Floris C.; de Vries, Maaike C.; Janssen, Mirian C. H.; van der Ploeg, Ans T.; Langendonk, Janneke G.; Huijbregts, Stephan C. J.

2016-01-01

Early treatment of phenylketonuria (ET-PKU) prevents mental retardation, but many patients still show cognitive and mood problems. In this study, it was investigated whether ET-PKU-patients have specific phenylalanine (Phe-)related problems with respect to social-cognitive functioning and social

Long-Term Follow-Up of Cognition and Mental Health in Adult Phenylketonuria: A PKU-COBESO Study

NARCIS (Netherlands)

R. Jahja (Rianne); F.J. van Spronsen; L.M.J. de Sonneville (Leo); J.J. van der Meere (J.); A.M. Bosch (Annet); C.E.M. Hollak (Carla); M.E. Rubio-Gozalbo (Estela); M.C.G.J. Brouwers (M. C G J); F.C. Hofstede (Floris); M. de Vries (Maaike); M.C.H. Janssen (Mirian); A.T. van der Ploeg (Ans); J.G. Langendonk (Janneke); S.C.J. Huijbregts (Stephan C.J.)

2017-01-01

textabstractCognitive and mental health problems in individuals with the inherited metabolic disorder phenylketonuria (PKU) have often been associated with metabolic control and its history. For the present study executive functioning (EF) was assessed in 21 PKU patients during childhood (T1, mean

Epidemiology and clinical study of phenylketonuria (PKU patients in Khorasan Province; Norteast Iran

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Negar Morovatdar

2015-03-01

Full Text Available Epidemiology and clinical study of phenylketonuria (PKU patients in Khorasan Province; Norteast Iran Background: Phenylketonuria is an autosomal recessive disease. Early diagnosis is a important public health intervention to prevent neurological impairment .This study was designed to describe characteristics of phenylketonouria patients in Khorasan ,Northeast of Iran. Methods: We included all  patients suffering from PKU in khorasan until September 2013. We gathered the variables like diagnosis age , sib of parents, cause of asking physician and screening based diagnosis or clinical based diagnosis. We use descriptive statistics for analysis. Results: The mean age of diagnosis was 19 months .80% pku patients had a positive history of consanguineous marriage in their parents. Incidence of new cases that identified by screening in 2012-2013 was 57 per 1000000 live birth. 10% patients identified with screening in first week of birth. Conclusion: Nearly all of our patients (90% had been diagnosed without screening in the first days of their life only due to clinical manifestations in the first year of their life . According to efficacy of early diagnosis and dietary treatment, enforcement of public health policy for screening is a critical public health preventive intervention.

Prenatal Maternal Smoking and Increased Risk for Tourette Syndrome and Chronic Tic Disorders.

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Browne, Heidi A; Modabbernia, Amirhossein; Buxbaum, Joseph D; Hansen, Stefan N; Schendel, Diana E; Parner, Erik T; Reichenberg, Abraham; Grice, Dorothy E

2016-09-01

We assessed the role of prenatal maternal smoking in risk for Tourette syndrome and chronic tic disorder (TS/CT) and pediatric-onset obsessive-compulsive disorder (OCD). In an analysis of 73,073 singleton pregnancies from the Danish National Birth Cohort, we calculated incidence rates (IR) per 1,000 person-year for TS/CT and OCD. We then determined crude and adjusted hazard ratios and 95% CIs associated with prenatal maternal smoking, considering smoking as a dichotomous (yes/no) variable or a stratified variable (no smoking, light smoking, and heavy smoking [≥10 cigarettes/day]). Additional analyses examined the effect of maternal smoking on risk for TS/CT with other comorbid psychiatric conditions. In final adjusted analyses, heavy smoking was associated with a 66% increased risk for TS/CT (adjusted hazard ratio = 1.66, 95% CI = 1.17-2.35). In addition, heavy smoking was associated with a 2-fold increased risk for TS/CT with comorbid attention-deficit/hyperactivity disorder (ADHD), and both light and heavy smoking were associated with a more than 2-fold increased risk for TS/CT with any non-ADHD psychiatric comorbidity. Our parallel analyses of pediatric-onset OCD were likely underpowered but showed similar relationships. Prenatal maternal smoking was associated with increased risk for TS/CT as well as TS/CT with comorbid psychiatric conditions, even after adjustment for several important variables, including maternal psychiatric history, socioeconomic status, and partner smoking. Our findings point to a pathway linking prenatal tobacco exposure and altered brain development to TS/CT. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Maternal responsivity in mothers of young children with Down syndrome.

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Sterling, Audra; Warren, Steven F

2014-10-01

The purpose of this study was to examine maternal responsivity and directive behaviors in mothers of children with Down syndrome (DS). Participants included 22 mothers with a young child with DS compared to 22 mothers of chronologically age-matched typically developing (TD) children using a cross-sectional design. The dyads participated in videotaped structured activities that were coded for responsive and directive behaviors. RESULTS indicated that the mothers of children with DS used a more facilitative style with the older children while these behaviors decreased with older children with TD; one directive behavior, request for behavioral comply, increased with the older children with DS. The mothers of children with DS adapted their parenting style to be facilitative of their children's linguistic development.

Maternal Choline Supplementation: A Potential Prenatal Treatment for Down Syndrome and Alzheimer's Disease.

Science.gov (United States)

Strupp, Barbara J; Powers, Brian E; Velazquez, Ramon; Ash, Jessica A; Kelley, Christy M; Alldred, Melissa J; Strawderman, Myla; Caudill, Marie A; Mufson, Elliott J; Ginsberg, Stephen D

2016-01-01

Although Down syndrome (DS) can be diagnosed prenatally, currently there are no effective treatments to lessen the intellectual disability (ID) which is a hallmark of this disorder. Furthermore, starting as early as the third decade of life, DS individuals exhibit the neuropathological hallmarks of Alzheimer's disease (AD) with subsequent dementia, adding substantial emotional and financial burden to their families and society at large. A potential therapeutic strategy emerging from the study of trisomic mouse models of DS is to supplement the maternal diet with additional choline during pregnancy and lactation. Studies demonstrate that maternal choline supplementation (MCS) markedly improves spatial cognition and attentional function, as well as normalizes adult hippocampal neurogenesis and offers protection to basal forebrain cholinergic neurons (BFCNs) in the Ts65Dn mouse model of DS. These effects on neurogenesis and BFCNs correlate significantly with spatial cognition, suggesting functional relationships. In this review, we highlight some of these provocative findings, which suggest that supplementing the maternal diet with additional choline may serve as an effective and safe prenatal strategy for improving cognitive, affective, and neural functioning in DS. In light of growing evidence that all pregnancies would benefit from increased maternal choline intake, this type of recommendation could be given to all pregnant women, thereby providing a very early intervention for individuals with DS, and include babies born to mothers unaware that they are carrying a fetus with DS.

Diet in phenylketonuria : A snapshot of special dietary costs and reimbursement systems in 10 international centers

NARCIS (Netherlands)

Belanger-Quintana, A.; Dokoupil, K.; Gokmen-Ozel, H.; Lammardo, A. M.; MacDonald, A.; Motzfeldt, K.; Nowacka, M.; van Rijn, M.; Ahring, K.; Robert, M.

Background and aims: To gather exploratory data on the costs and reimbursement of special dietary foods used in the management of phenylketonuria (PKU) from ten international specialist PKU centers. Methods: Experts from each center provided data on retail costs of the three most frequently used

Severe hypertensive syndrome – descriptive study with adolescents attended at a maternity school

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Andreia Gregório Lima

2012-06-01

Full Text Available This is an exploratory and descriptive study with the objective of analyzing the clinical and obstetric data related to the severe hypertensive disorders in adolescents assisted at a maternity school of Recife. The population was consisted of 186 pregnant adolescents with severe preeclampsia and/or eclampsia between 2003 and 2008. The age ranged between 15 and 19 years; they were black, single and had low education. Most of them were primiparas but the pregnancy recurrence was configured at 16% of cases. They did six or more prenatal consultations. The pregnancy progressed to term and the most frequent type of delivery was cesarean section. The comorbidities identified were changes in amniotic fluid volume, hemorrhages and infections. There were also identified cases of intrauterine growth retardation, prematurity, jaundice, hypoxia and low birth weight. It was concluded that teenage pregnancy associated with severe hypertensive syndrome is related to severe maternal, fetal and neonatal complications.

Brain MR imaging in dietarily treated phenylketonuria

Energy Technology Data Exchange (ETDEWEB)

Breysem, L. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Smet, M.H. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Johannik, K. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Hecke, P. van [Dept. of Radiology, University Hospitals, Leuven (Belgium); Francois, B. [L. Willems Inst., Diepenbeek (Belgium); Wilms, G. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Bosmans, H. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Marchal, G. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Jaeken, J. [Dept. of Pediatrics, University Hospitals, Leuven (Belgium); Demaerel, P. [Dept. of Radiology, University Hospitals, Leuven (Belgium)

1994-08-01

Magnetic resonance imaging is the most efficient imaging modality to evaluate brain gray and white matter of patients with metabolic diseases. The main purpose of our study was to investigate the relation between brain MRI abnormalities and the phenylalanine (phe) and tyrosine (tyr) blood levels in 38 phenylketonuria (PKU) patients. Increased periventricular white matter intensity on T2-weighted brain images was the only pathologic finding in 24 patients. Brain MRI abnormalities were scored (4) and correlated with the individual mean phe and phe/tyr levels during 1 year preceding MR examination and with phe tolerance. The residual activity of phenylalanine hydroxylase was defined for each patient by an oral phe tolerance. The appearance of MRI abnormalities on brain T2-weighted images correlates with a threshold mean phe level (averaged over the year preceding the examination). (orig.)

Brain MR imaging in dietarily treated phenylketonuria

International Nuclear Information System (INIS)

Breysem, L.; Smet, M.H.; Johannik, K.; Hecke, P. van; Francois, B.; Wilms, G.; Bosmans, H.; Marchal, G.; Jaeken, J.; Demaerel, P.

1994-01-01

Magnetic resonance imaging is the most efficient imaging modality to evaluate brain gray and white matter of patients with metabolic diseases. The main purpose of our study was to investigate the relation between brain MRI abnormalities and the phenylalanine (phe) and tyrosine (tyr) blood levels in 38 phenylketonuria (PKU) patients. Increased periventricular white matter intensity on T2-weighted brain images was the only pathologic finding in 24 patients. Brain MRI abnormalities were scored (4) and correlated with the individual mean phe and phe/tyr levels during 1 year preceding MR examination and with phe tolerance. The residual activity of phenylalanine hydroxylase was defined for each patient by an oral phe tolerance. The appearance of MRI abnormalities on brain T2-weighted images correlates with a threshold mean phe level (averaged over the year preceding the examination). (orig.)

Maternal methylenetetrahydrofolate reductase C677T polymorphism and down syndrome risk: a meta-analysis from 34 studies.

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Vandana Rai

Full Text Available Methylenetetrahydrofolate reductase (MTHFR is a key enzyme of folate metabolic pathway which catalyzes the irreversible conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. 5-methyltetrahydrofolate donates methyl group for the methylation of homocysteine to methionine. Several studies have investigated maternal MTHFR C677T polymorphism as a risk factor for DS, but the results were controversial and inconclusive. To come into a conclusive estimate, authors performed a meta-analysis.A meta-analysis of published case control studies was performed to investigate the association between maternal MTHFR C677T polymorphism and Down syndrome.PubMed, Google Scholar, Elsevier, Springer Link databases were searched to select the eligible case control studies using appropriate keywords. The pooled odds ratio (OR with 95%confidence interval were calculated for risk assessment.Thirty four studies with 3,098 DS case mothers and 4,852 control mothers were included in the present meta-analysis. The pooled OR was estimated under five genetic models and significant association was found between maternal MTHFR 677C>T polymorphism and Down syndrome under four genetic models except recessive model (for T vs. C, OR = 1.26, 95% CI = 1.09-1.46, p = 0.001; for TT vs. CC, OR = 1.49, 95% CI = 1.13-1.97, p = 0.008; for CT vs. CC, OR = 1.29, 95% CI = 1.10-1.51, p = 0.001; for TT+CT vs. CC, OR = 1.35, 95% CI = 1.13-1.60, p = 0.0008; for TT vs. CT+CC, OR = 0.76, 95% CI = 0.60-0.94, p = 0.01.The results of the present meta-analysis support that maternal MTHFR C677T polymorphism is a risk factor for DS- affected pregnancy.

Abnormal tyrosine and phenylalanine metabolism in patients with tyrosyluria and phenylketonuria; gas-liquid chromatographic analysis of urinary metabolites

NARCIS (Netherlands)

Wadman, S.K.; Heiden, C. van der; Ketting, D.; Sprang, F.J. van

Gas-liquid chromatographic methods have been developed for the analysis of: urinary phenylalanine metabolites (I) in patients with phenylketonuria, tyrosine metabolites (II) in patients with a disturbed tyrosine metabolism at the level of p-hydroxyphenylpyruvate hydroxylase, and homogentisic acid in

Perceptual-motor functioning in children with phenylketonuria.

Science.gov (United States)

Koff, E; Boyle, P; Pueschel, S M

1977-10-01

Children with treated phenylketonuria (PKU) have been described as being at high risk for perceptual-motor dysfunction. In this study, the Wechsler Intelligence Scale for Children (WISC) and the Bender Gestalt test were administered to 19 school age children with treated PKU and of average intelligence who have been off diet from five months to six years four months. Perceptual-motor performance was evaluated, and school functioning was rated by classroom teachers. Substantial impairment of perceptual-motor functioning as measured by the Bender Gestalt test and lower WISC performance IQs than verbal IQs were observed in children of average intelligence. Quality of dietary control was found to be associated with performance on the Bender Gestalt test. These findings suggest the possibility of a specific deficit that could seriously interfere with academic progress, but which is not signalled by obvious impairment of overall intellectual functioning.

Chilean Nutrition Management Protocol for Patients With Phenylketonuria

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Gabriela Castro

2017-02-01

Full Text Available Since neonatal screening and early nutritional treatment began, it has been possible to reverse the neurological damage that phenylketonuria (PKU causes. Scientific evidence gathered over more than 50 years on the monitoring of individuals with PKU indicates that a phenylalanine level of about 6 mg/dL (360 µmol/L is ideal and points to the necessity of starting a long-term phenylalanine-restricted diet in which blood phenylalanine level should stay between 2 and 6 mg/dL (120-360 µmol/L. This article aims to establish the general basis for proper monitoring of people with PKU and provide a useful tool for clinicians overseeing treatment. We hope to establish similar criteria throughout Latin America and create a uniform protocol in order to have comparative monitoring results for the region.

Elevated second-trimester maternal serum β-human chorionic gonadotropin and amniotic fluid alpha-fetoprotein as indicators of adverse obstetric outcomes in fetal Turner syndrome.

Science.gov (United States)

Alvarez-Nava, Francisco; Soto, Marisol; Lanes, Roberto; Pons, Hector; Morales-Machin, Alisandra; Bracho, Ana

2015-12-01

The objective of this study was to determine the ability of biochemical analytes to identify adverse outcomes in pregnancies with Turner syndrome. Maternal serum and amniotic fluid (AF) marker concentrations were measured in 73 singleton pregnancies with Turner syndrome (10-22 weeks of gestation). Fetal Turner syndrome was definitively established by cytogenetic analysis. Two subgroups, fetuses with hydrops fetalis versus fetuses with cystic hygroma, were compared. Receiver operating characteristic curves and relative risk were established for a cut-off multiples of the median ≥3.5 for β-subunit of human chorionic gonadotropin (hCG) or AF alpha-fetoprotein (AFP). Forty-nine (67%) of 73 pregnant women had an abnormal maternal serum. While levels of pregnancy-associated plasma protein-A and free β-subunit (fβ)-hCG were not different to those of the control group, AFP, unconjugated estriol and β-hCG concentrations were significantly different in the study group (P Turner syndrome pregnancies with the highest risk of fetal death. © 2015 Japan Society of Obstetrics and Gynecology.

Co-variables in first trimester maternal serum screening

NARCIS (Netherlands)

de Graaf, I. M.; Cuckle, H. S.; Pajkrt, E.; Leschot, N. J.; Bleker, O. P.; van Lith, J. M.

2000-01-01

The objective of this study was to determined the influence of maternal weight, maternal smoking habits, gravidity, parity and fetal gender on the level of maternal serum marker used in first trimester screening for Down syndrome. A total of 2449 singleton unaffected pregnancies from two centres

Comparison of epidermal keratinocytes and dermal fibroblasts as potential target cells for somatic gene therapy of phenylketonuria

DEFF Research Database (Denmark)

Christensen, Rikke; Güttler, Flemming; Jensen, Thomas G

2002-01-01

Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase (PAH) and increased levels of phenylalanine. PAH requires the cofactor BH(4) to function and the rate-limiting step in the synthesis of BH(4) is GTP cyclohydrolase I (GTP-CH). The skin is a potential target tissue for PKU...

Maternal risk factors in fetal alcohol syndrome: provocative and permissive influences.

Science.gov (United States)

Abel, E L; Hannigan, J H

1995-01-01

We present an hypothesis integrating epidemiological, clinical case, and basic biomedical research to explain why only relatively few women who drink alcohol during pregnancy give birth to children with alcohol-related birth defects (ARBDs), in particular, Fetal Alcohol Syndrome (FAS). We argue that specific sociobehavioral risk factors, e.g., low socioeconomic status, are permissive for FAS in that they provide the context for increased vulnerability. We illustrate how these permissive factors are related to biological factors, e.g., decreased antioxidant status, which in conjunction with alcohol, provoke FAS/ARBDs in vulnerable fetuses. We propose an integrative heuristic model hypothesizing that these permissive and provocative factors increase the likelihood of FAS/ARBDs because they potentiate two related mechanisms of alcohol-induced teratogenesis, specifically, maternal/fetal hypoxia and free radical formation.

Phenylketonuria as a model for protein misfolding diseases and for the development of next generation orphan drugs for patients with inborn errors of metabolism.

Science.gov (United States)

Muntau, Ania C; Gersting, Søren W

2010-12-01

The lecture dedicated to Professor Horst Bickel describes the advances, successes, and opportunities concerning the understanding of the biochemical and molecular basis of phenylketonuria and the innovative treatment strategies introduced for these patients during the last 60 years. These concepts were transferred to other inborn errors of metabolism and led to significant reduction in morbidity and to an improvement in quality of life. Important milestones were the successful development of a low-phenylalanine diet for phenylketonuria patients, the recognition of tetrahydrobiopterin as an option to treat these individuals pharmacologically, and finally market approval of this drug. The work related to the discovery of a pharmacological treatment led metabolic researchers and pediatricians to new insights into the molecular processes linked to mutations in the phenylalanine hydroxylase gene at the cellular and structural level. Again, phenylketonuria became a prototype disorder for a previously underestimated but now rapidly expanding group of diseases: protein misfolding disorders with loss of function. Due to potential general biological mechanisms underlying these disorders, the door may soon open to a systematic development of a new class of pharmaceutical products. These pharmacological chaperones are likely to correct misfolding of proteins involved in numerous genetic and nongenetic diseases.

Trisomy 15 with loss of the paternal 15 as a cause of Prader-Willi syndrome due to maternal disomy

Energy Technology Data Exchange (ETDEWEB)

Cassidy, S.B.; Lai, Li-Wen; Erickson, R.P. (Univ. of Arizona College of Medicine, Tucson, AZ (United States)); Magnuson, L.; Thomas, E.; Herrmann, J. (Great Lakes Genetics, Milwaukee, AZ (United States)); Gendron, R. (Great Lakes Genetics, Kingsport, TN (United States))

1992-10-01

Uniparental disomy has recently been recognized to cause human disorders, including Prader-Willi syndrome (PWS). The authors describe a particularly instructive case which raises important issues concerning the mechanisms producing uniparental disomy and whose evaluation provides evidence that trisomy may precede uniparental disomy in a fetus. Chorionic villus sampling performed for advanced maternal age revealed trisomy 15 in all direct and cultured cells, though the fetus appeared normal. Chromosome analysis of amniocytes obtained at 15 wk was normal in over 100 cells studied. The child was hypotonic at birth, and high-resolution banding failed to reveal the deletion of 15q11-13, a deletion which is found in 50%-70% of patients with PWS. Over time, typical features of PWS developed. Molecular genetic analysis using probes for chromosome 15 revealed maternal disomy. Maternal nondisjunction with fertilization of a disomic egg by a normal sperm, followed by loss of the paternal 15, is a likely cause of confined placental mosaicism and uniparental disomy in this case of PWS, and advanced maternal age may be a predisposing factor. 38 refs., 3 figs., 2 tabs.

Alterações auditivas e fenilcetonúria: uma revisão sistemática Hearing disorders and phenylketonuria: a systematic review

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Patrícia Cotta Mancini

2010-02-01

Full Text Available TEMA: a fenilcetonúria é uma doença genética que provoca alterações bioquímicas conduzindo a uma deficiência na síntese de proteínas e de neurotransmissores, e prejudicando o processo de mielinização. Mudanças estruturais e funcionais da mielina podem alterar os padrões de condutividade neuronal e ou diminuir a conexão sináptica em indivíduos com fenilcetonúria. Essencialmente, um tratamento dietético deve ser realizado dentro das primeiras semanas de vida para evitar as manifestações clínicas e bioquímicas da doença. Quando a dieta é mantida ininterruptamente, as crianças com fenilcetonúria apresentam desenvolvimento normal. Porém, foram observados déficits em funções executivas, na interação inter-hemisférica, na linguagem e memória mesmo em crianças com tratamento precoce e dieta adequada. Algumas pesquisas foram realizadas para investigação da relação entre fenilcetonúria e alterações auditivas. OBJETIVO: rever de forma sistemática os artigos científicos dedicados à pesquisa da relação entre alterações auditivas e hiperfenilalaninemias, destacando a fenilcetonúria clássica. As referências bibliográficas foram obtidas por meio de pesquisa nas bases de dados Lilacs, Medline, Biblioteca Cochrane e Scielo e por busca na lista de referência dos artigos identificados e selecionados. CONCLUSÃO: conclui-se que a relação entre hiperfenilalaninemias, incluindo a fenilcetonúria, e alterações auditivas ainda é controversa na literatura. Sugere-se a realização de mais investigações sobre a função auditiva nesses indivíduos a fim de elucidar essa possível relação.BACKGROUND: phenylketonuria is a genetic disorder that causes biochemical alterations, leading to a deficiency in the synthesis of proteins and neurotransmitters and thereby hindering the myelination process. Structural and functional changes in myelin can alter neural conductivity patterns and or reduce synaptic connection

Mosaicism for maternal uniparental disomy 15 in a boy with some clinical features of Prader-Willi syndrome.

Science.gov (United States)

Zilina, Olga; Kahre, Tiina; Talvik, Inga; Oiglane-Shlik, Eve; Tillmann, Vallo; Ounap, Katrin

2014-01-01

Prader-Willi syndrome (PWS) is caused by the lack of paternal expression of imprinted genes in the human chromosomal region 15q11.2-q13.2, which can be due to an interstitial deletion at 15q11.2-q13 of paternal origin (65-75%), maternal uniparental disomy (matUPD) of chromosome 15 (20-30%), or an imprinting defect (1-3%). The majority of PWS-associated matUPD15 cases represent a complete heterodisomy of chromosome 15 or a mixture of hetero- and isodisomic regions across the chromosome 15. Pure maternal isodisomy is observed in only a few matUPD15 patients. Here we report a case of an 18-year-old boy with some clinical features of Prader-Willi syndrome, such as overweight, muscular hypotonia, facial dysmorphism and psychiatric problems, but there was no reason to suspect PWS in the patient based solely on the phenotype estimation. However, chromosomal microarray analysis (CMA) revealed mosaic loss of heterozygosity of the entire chromosome 15. Methylation-specific multiplex ligation-dependant probe amplification (MS-MLPA) analysis showed hypermethylation of the SNRPN and NDN genes in the PWS/AS critical region of chromosome 15 in this patient. Taking into consideration the MS-MLPA results and the presence of PWS features in the patient, we concluded that it was matUPD15, although the patient's parents were not enrolled in the study. According to CMA and karyotyping, no trisomic or monosomic cells were present. To the best of our knowledge, only two PWS cases with mosaic maternal isodisomy 15 and without trisomic/monosomic cell lines have been reported so far. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

An Investigation of the Neurological and Neuropsychiatric Disturbances in Adults with Undiagnosed and/or Untreated Phenylketonuria in Poland

Science.gov (United States)

Mazur, Artur; Jarochowicz, Sabina; Oltarzewski, Mariusz; Sykut-Cegielska, Jolanta; Gradowska, Wanda; Januszek-Trzciakowska, Aleksandra; O'Malley, Grace; Kwolek, Andrzej

2011-01-01

Background: The aim of the study was to determine neurological and neuropsychiatric manifestations in a group of patients with previously undiagnosed or untreated phenylketonuria (PKU) in the south-eastern part of Poland. Methods: The study was conducted among 400 adults with severe intellectual disability who were born prior to neonatal screening…

Metabolic syndrome in Spanish adolescents and its association with birth weight, breastfeeding duration, maternal smoking, and maternal obesity: a cross-sectional study.

Science.gov (United States)

González-Jiménez, Emilio; Montero-Alonso, Miguel A; Schmidt-RioValle, Jacqueline; García-García, Carmen J; Padez, Cristina

2015-06-01

The metabolic syndrome (MetS) in adolescents is a growing problem. The objectives were to verify the association among early predictors such as birth weight, breastfeeding, maternal weight status, smoking during pregnancy, and the development of MetS. A cross-sectional study was performed of 976 children and adolescents, 10-15 years of age, at schools in the provinces of Granada and Almeria (Spain). For this purpose, we analyzed the physical characteristics as well as the biochemical markers of the participants with a view to ascertaining the prevalence of the MetS. Relevant data were also extracted from the clinical histories of their mothers. It was found that 3.85% of the female subjects and 5.38% of the male subjects in the sample population suffered from MetS. In both sexes, there was an association between birth weight and positive MetS diagnosis (OR 1.27). For both males and females, there was an inverse association between the length of time that they had been breastfed and positive MetS diagnosis (OR1-3 months 3.16; OR4-6 months 1.70; OR(>6 months) 0.13). There was also a significant association between maternal weight (OR(overweight )30.79; OR(obesity) 49.36) and cigarette consumption during pregnancy (OR 1.47) and the subsequent development of MetS in the children of these mothers. Those subjects born with a higher than average birth weight had a greater risk of developing MetS in childhood and adolescence. Breastfeeding children for longer than 6 months protected them from MetS in their early years as well as in their teens. Other risk factors for MetS were maternal smoking during pregnancy as well as maternal overweight and obesity.

MR in phenylketonuria-related brain lesions

International Nuclear Information System (INIS)

Dezortova, M.; Hajek, M.; Tintra, J.; Hejcmanova, L.; Sykova, E.

2001-01-01

Purpose: Phenylketonuria (PKU) patients were examined by different MR techniques to explain the pathological changes observed in periventricular white brain matter using conventional MR imaging. Material and Methods: Fifteen patients with treated classical PKU were examined by 1 H spectroscopy, relaxometry and diffusion imaging on a whole-body 1.5-T MR imager. Results: Known PKU lesions characterized by T2 enhancement in periventricular white matter were observed in all patients. The MR spectra from the lesioned areas showed a significant decrease in choline concentration. The mean ADC of water decreased and tortuosity increased in PKU lesions compared to control data. Conclusion: The results support the following hypothesis: The T2 increase in the PKU lesion reflects a raised concentration of free water molecules (about 15%) that have an increased trajectory between collisions compared to the same region in controls. The increase in water mobility might be explained by changes in extracellular space volume and myelin sheaths, which, presumably, have a different geometry with more hydrophobic sites in PKU patients. The changes result in increased tortuosity and may be confirmed by the loss of anisotropy in PKU lesions

MR in phenylketonuria-related brain lesions

Energy Technology Data Exchange (ETDEWEB)

Dezortova, M.; Hajek, M.; Tintra, J. [Inst. for Clinical and Experimental Medicine, Prague (Czech Republic); Hejcmanova, L. [Charles University, Prague (Czech Republic). 3rd Medical Faculty; Sykova, E. [Charles University, Prague (Czech Republic). 2nd Medical Faculty

2001-09-01

Purpose: Phenylketonuria (PKU) patients were examined by different MR techniques to explain the pathological changes observed in periventricular white brain matter using conventional MR imaging. Material and Methods: Fifteen patients with treated classical PKU were examined by {sup 1}H spectroscopy, relaxometry and diffusion imaging on a whole-body 1.5-T MR imager. Results: Known PKU lesions characterized by T2 enhancement in periventricular white matter were observed in all patients. The MR spectra from the lesioned areas showed a significant decrease in choline concentration. The mean ADC of water decreased and tortuosity increased in PKU lesions compared to control data. Conclusion: The results support the following hypothesis: The T2 increase in the PKU lesion reflects a raised concentration of free water molecules (about 15%) that have an increased trajectory between collisions compared to the same region in controls. The increase in water mobility might be explained by changes in extracellular space volume and myelin sheaths, which, presumably, have a different geometry with more hydrophobic sites in PKU patients. The changes result in increased tortuosity and may be confirmed by the loss of anisotropy in PKU lesions.

Requirements for a minimum standard of care for phenylketonuria: the patients’ perspective

Science.gov (United States)

2013-01-01

Phenylketonuria (PKU, ORPHA716) is an inherited disorder that affects about one in every 10,000 children born in Europe. Early and continuous application of a modified diet is largely successful in preventing the devastating brain damage associated with untreated PKU. The management of PKU is inconsistent: there are few national guidelines, and these tend to be incomplete and implemented sporadically. In this article, the first-ever pan- European patient/carer perspective on optimal PKU care, the European Society for Phenylketonuria and Allied Disorders (E.S.PKU) proposes recommendations for a minimum standard of care for PKU, to underpin the development of new pan-European guideline for the management of PKU. New standards of best practice should guarantee equal access to screening, treatment and monitoring throughout Europe. Screening protocols and interpretation of screening results should be standardised. Experienced Centres of Expertise are required, in line with current European Union policy, to guarantee a defined standard of multidisciplinary treatment and care for all medical and social aspects of PKU. Women of childbearing age require especially intensive management, due to the risk of severe risks to the foetus conferred by uncontrolled PKU. All aspects of treatment should be reimbursed to ensure uniform access across Europe to guideline-driven, evidence-based care. The E.S.PKU urges PKU healthcare professionals caring for people with PKU to take the lead in developing evidence based guidelines on PKU, while continuing to play an active role in serving as the voice of patients and their families, whose lives are affected by the condition. PMID:24341788

Surface-enhanced Raman scattering (SERS) for detection of phenylketonuria for newborn screening

Science.gov (United States)

Javanmard, M.; Davis, R. W.

2014-02-01

Diagnosis of Phenylketonuria (PKU) in newborns is important because it can potentially help prevent mental retardation since it is treatable by dietary means. PKU results in phenylketonurics having phenylalanine levels as high as 2 mM whereas the normal upper limit in healthy newborns is 120 uM. To this end, we are developing a microfluidic platform integrated with a SERS substrate for detection of high levels of phenylalanine. We have successfully demonstrated SERS detection of phenylalanine using various SERS substrates fabricated using nanosphere lithography, which exhibit high levels of field enhancement. We show detection of SERS at clinically relevant levels.

Achados audiológicos em crianças com fenilcetonúria Audiologic findings in children with phenylketonuria

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Patrícia Cotta Mancini

2010-01-01

Full Text Available OBJETIVO: Investigar a existência de alterações na audição de crianças com fenilcetonúria diagnosticadas e tratadas precocemente e comparar os resultados com os encontrados nas avaliações auditivas de crianças normais de mesma idade. MÉTODOS: Foram realizadas imitanciometria e audiometria tonal e vocal em 63 crianças, sendo 30 no grupo controle, com média de idade de 8,1 anos, e 33 com fenilcetonúria no grupo de estudo, com média de idade de 7,7 anos. O grupo de estudo foi subdividido em 15 crianças com controle adequado da dieta e 18 crianças com controle inadequado da dieta, com médias de idade 8,1 e 7,2, respectivamente. A análise estatística utilizou o Teste t ou ANOVA. RESULTADOS: A audiometria revelou 83,3% de crianças com audição normal no grupo controle e 16,7% de perdas auditivas condutivas uni ou bilaterais. No grupo com fenilcetonúria, 66,7% das crianças apresentaram audição normal e 33,3% com perdas auditivas condutivas. Na imitanciometria, observou-se curvas normais em 91,7% das crianças do grupo controle e em 72,7% das crianças do grupo com fenilcetonúria. Houve diferença na comparação entre grupos para limiares aéreos, reflexos estapedianos, limiares de recepção da fala e índice de reconhecimento de fala. Não foi observada diferença entre os resultados das avaliações auditivas de crianças fenilcetonúricas com dieta adequada e inadequada. CONCLUSÃO: As crianças com fenilcetonúria diagnosticadas e tratadas precocemente apresentaram piores limiares de audibilidade por via aérea, limiares de recepção de fala e índice de reconhecimento de fala evidenciados à audiometria tonal e vocal, quando comparadas com crianças normais.PURPOSE: To investigate the existence of hearing impairments in infants with phenylketonuria with early diagnose and treatment, and to compare the audiological findings with those of their normal peers. METHODS: Vocal and pure-tone audiometry and acoustic immitance

Infection and acute respiratory distress syndrome during pregnancy: a case series of preventable maternal deaths from southern India.

Science.gov (United States)

Vasudeva, Akhila; Bhat, Rajeshwari G; Ramachandran, Amar; Kumar, Pratap

2013-02-01

Acute respiratory distress syndrome (ARDS) is common among women admitted to obstetric intensive care units, and it contributes significantly, both directly and indirectly, to maternal deaths. We present a case series of ARDS in pregnant women caused by non-obstetric causes. The women were treated at a tertiary hospital in southern India. The striking features were delayed referral from the primary care unit and the lack of a primary diagnosis or treatment. Undiagnosed rheumatic heart disease, anemia, and malaria and H1N1 epidemics contributed to these cases of ARDS and maternal death. It is necessary to increase the awareness of evidence-based uniform protocols to tackle common medical complaints during pregnancy. Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Whole body composition analysis by the BodPod air-displacement plethysmography method in children with phenylketonuria shows a higher body fat percentage

NARCIS (Netherlands)

Albersen, Monique; Bonthuis, Marjolein; de Roos, Nicole M.; van den Hurk, Dorine A. M.; Weber, Ems Carbasius; Hendriks, Margriet M. W. B.; de Sain-van der Velden, Monique G. M.; de Koning, Tom J.; Visser, Gepke

2010-01-01

BACKGROUND: Phenylketonuria (PKU) causes irreversible central nervous system damage unless a phenylalanine (PHE) restricted diet with amino acid supplementation is maintained. To prevent growth retardation, a protein/amino acid intake beyond the recommended dietary protein allowance is mandatory.

Total bile acids in the maternal and fetal compartment in relation to placental ABCG2 expression in preeclamptic pregnancies complicated by HELLP syndrome

NARCIS (Netherlands)

Jebbink, Jiska; Veenboer, Geertruda; Boussata, Souad; Keijser, Remco; Kremer, Andreas E.; Elferink, Ronald Oude; van der Post, Joris; Afink, Gijs; Ris-Stalpers, Carrie

2015-01-01

To investigate total bile acid (TBA) levels in maternal (MB) and umbilical cord blood (UCB) in normotensive, preeclamptic (PE), and PE pregnancies complicated by hemolysis elevated liver enzymes and low platelets (HELLP) syndrome in the context of ABCG2 placental gene expression levels, a recently

LEOPARD-syndrom

DEFF Research Database (Denmark)

Hansen, Lars Kjaersgård; Risby, Kirsten; Bygum, Anette

2009-01-01

We describe a 12-year-old boy with a typical phenotype of the LEOPARD syndrome (LS). The diagnosis was confirmed in the boy and his mother, who both had a mutation in the PTPN11 gene at Thr468Met (c.1403C > T). Several other members of the maternal family are suspected also to have the LEOPARD sy...... syndrome. We discuss the clinical characteristics of LS, the need for follow-up and genetic counselling, and the molecular-genetic background as well as the relationship to the allelic disease Noonan syndrome. Udgivelsesdato: 2009-Jan-26......We describe a 12-year-old boy with a typical phenotype of the LEOPARD syndrome (LS). The diagnosis was confirmed in the boy and his mother, who both had a mutation in the PTPN11 gene at Thr468Met (c.1403C > T). Several other members of the maternal family are suspected also to have the LEOPARD...

Unexpected Maternal Convulsion: An Idiopathic Case of Posterior Reversible Encephalopathy Syndrome after Delivery

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Jila Agah

2016-01-01

Full Text Available Posterior reversible encephalopathy syndrome (PRES is associated with various clinical manifestations such as headache, blurred vision, confusion and tonic-clonic convulsion. Some of the predisposing factors for PRES include hypertensive encephalopathy, preeclampsia and eclampsia, lupus erythematosus, thrombotic thrombocytopenic purpura and long-term use of immunosuppressive drugs. This condition rarely occurs after normotensive and uneventful pregnancies. Several theories have been proposed on the etiology of PRES. For instance, endothelial injury and brain edema have been reported as possible causes of PRES. Although PRES is a temporary condition, proper and timely management of the disorder in the acute phase is critical for the prevention of permanent neurological complications. During pregnancy, PRES is normally accompanied with hypertension. In this paper, we present a rare case of PRES in a normotensive pregnancy in a 25-year-old parturient woman (Gravida 2, Ab 1. The patient unexpectedly manifested symptoms of tonic-clonic convulsion one hour after an uneventful vaginal delivery, which were successfully managed. According to our observations, PRES has various clinical manifestations with unexpected occurrence in some cases. Therefore, it is recommended that maternity centers be well-equipped with resuscitation tools, emergency drugs and expert staff so as to manage unforeseen PRES efficiently and prevent permanent maternal neurological complications and mortality.

Genetics of Phenylketonuria: Then and Now.

Science.gov (United States)

Blau, Nenad

2016-06-01

More than 950 phenylalanine hydroxylase (PAH) gene variants have been identified in people with phenylketonuria (PKU). These vary in their consequences for the residual level of PAH activity, from having little or no effect to abolishing PAH activity completely. Advances in genotyping technology and the availability of locus-specific and genotype databases have greatly expanded our understanding of the correlations between individual gene variant, residual PAH activity, tetrahydrobiopterin (BH4 ) responsiveness, and the clinical PKU phenotype. Most patients (∼76%) have compound heterozygous PAH gene variants and one mutated allele may markedly influence the activity of the second mutated allele, which in turn may influence either positively or negatively the activity of the biologically active heterotetrameric form of the PAH. While it is possible to predict the level of BH4 responsiveness (∼71%) and PKU severity (∼78%) from the nature of the underlying gene variants, these relationships remain complex and incompletely understood. A greater understanding of these relationships may increase the potential for individualized management of PKU in future. Inherited deficiencies in BH4 metabolism account for about 1%-2% of all hyperphenylalaninemias and are clinically more severe than PKU. Almost 90% of all patients are deficient in 6-pyruvoyl-tetrahydropterin synthase and dihydropteridine reductase. © 2016 WILEY PERIODICALS, INC.

Plasma phenylalanine and tyrosine responses to different nutritional conditions (fasting/postprandial) in patients with phenylketonuria: effect of sample timing.

Science.gov (United States)

van Spronsen, F J; van Rijn, M; van Dijk, T; Smit, G P; Reijngoud, D J; Berger, R; Heymans, H S

1993-10-01

To evaluate the adequacy of dietary treatment in patients with phenylketonuria, the monitoring of plasma phenylalanine and tyrosine concentrations is of great importance. The preferable time of blood sampling in relation to the nutritional condition during the day, however, is not known. It was the aim of this study to define guidelines for the timing of blood sampling with a minimal burden for the patient. Plasma concentrations of phenylalanine and tyrosine were measured in nine patients with phenylketonuria who had no clinical evidence of tyrosine deficiency. These values were measured during the day both after a prolonged overnight fast, and before and after breakfast. Phenylalanine showed a small rise during prolonged fasting, while tyrosine decreased slightly. After an individually tailored breakfast, phenylalanine remained stable, while tyrosine showed large fluctuations. It is concluded that the patient's nutritional condition (fasting/postprandial) is not important in the evaluation of the phenylalanine intake. To detect a possible tyrosine deficiency, however, a single blood sample is not sufficient and a combination of a preprandial and postprandial blood sample on the same day is advocated.

Screening Children with Autism for Fragile-X Syndrome and Phenylketonuria. Brief Report.

Science.gov (United States)

Pueschel, Siegfried M.; And Others

1985-01-01

Family histories, comprehensive physical examinations, and chromosome analyses of 35 males with autism were performed. Results indicated that the fragile X syndrome may be present in less than 16 percent of persons whose family history or physical features suggest the condition's possible presence. Screening 42 autistic children for…

Prader-Willi syndrome and Tay-Sachs disease in association with mixed maternal uniparental isodisomy and heterodisomy 15 in a girl who also had isochromosome Xq.

Science.gov (United States)

Zeesman, Susan; McCready, Elizabeth; Sadikovic, Bekim; Nowaczyk, Małgorzata Jm

2015-01-01

Malsegregation of chromosomes during reproduction can result in uniparental disomy when associated with trisomy rescue, monosomy rescue or gamete complementation. Pathogenicity stemming from uniparental disomy in liveborns results from imprinting disorders or autozygosity for autosomal recessive disorders. We report on a girl with Prader-Willi syndrome and Tay-Sachs disease resulting from maternal uniparental disomy of chromosome 15. The child also had an isochromosome Xq. To further characterize the etiology of the aberrant chromosome 15 and the isochromosome Xq, SNP loci from both chromosomes were assessed in the proband and parents, and genome-wide DNA methylation analysis was performed. SNP and DNA methylation analysis confirmed maternal uniparental heterodisomy around the Prader-Willi locus, while the region around the HEXA locus showed maternal uniparental isodisomy. This result is consistent with trisomy rescue of a maternal meiosis l error in a chromosome 15 with two meiotic recombinations. SNP analysis of the X chromosomes is consistent with a maternal origin for the isochromosome. © 2014 Wiley Periodicals, Inc.

When should social service referral be considered in phenylketonuria?

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Margreet van Rijn

2015-03-01

Full Text Available Lifelong low-phenylalanine (Phe dietary management is the foundation of care in phenylketonuria (PKU. However, strict monitoring of food intake places a burden on patients and their caregivers, and adherence to the required diet frequently decreases in later childhood and adolescence. Rarely, parents of children with PKU refuse to recognise the importance of treatment and follow-up for this chronic condition. Here, two case studies are presented that document consideration of placement of children into foster care or kinship homes as a last resort to improve persistently high Phe concentrations. In the first case, social service referral led to a 3-year-old girl being placed in a kinship home with her grandparents, resulting in excellent Phe control thereafter. In the second case, discussion with the parents of possible placement of a 12-year-old child into foster care was sufficient to have a positive effect on Phe control. A staged approach for managing intractable non-adherence in PKU is proposed.

Associations of biochemical changes and maternal traits with mutation 1843 (C>T in the RYR1 gene as a common cause for porcine stress syndrome

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Popovski ZT

2016-12-01

Full Text Available Stress syndrome is usually caused by a mutation in the ryanodine receptor gene (ryr1 and it is widely studied in humans and swine populations. The protein product of this gene plays a crucial role in the regulation of calcium transport in muscle cells. A G>T mutation in the human ryr1 gene, which results in the replacement of a conserved arginine at position 614 where a leucine occurs at the same position as the previously identified Arg→Cys mutation reported in all cases of porcine stress syndrome (PSS. Porcine stress syndrome affects biochemical pathways in stress-susceptible individuals during a stress episode and some biochemical parameters that were used as markers for diagnostic purposes. Also, PSS has remarkable influence on the maternal characteristics of sows. This study dealt with different genotypes for PSS and its association with possible biochemical changes and maternal traits of sows. Seventy-three reproductive sows genotyped for PSS by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP were included in this survey. Sixty of them were stress-free (NN, 11 were heterozygous carriers (Nn and two animals were homozygous (nn for the 1843 (C>T mutation. Significant differences in non stress induced animals with different PSS genotypes were found in the values of creatine phoshokinase (CPK, lactate dehydrogenase (LDH, alkaline phosphatase (AP and aspartate aminotransferase (AST. Regarding the maternal traits, our study showed that stress susceptible animals (nn have an increased number of stillborn piglets and a reduced number of newborn piglets compared with heterozygous and normal animals.

The intake of total protein, natural protein and protein substitute and growth of height and head circumference in Dutch infants with phenylketonuria

NARCIS (Netherlands)

Hoeksma, M.; van Rijn, M. [=Margreet; Verkerk, P. H.; Bosch, A. M.; Mulder, M. F.; de Klerk, J. B. C.; de Koning, T. J.; Rubio-Gozalbo, E.; de Vries, M.; Sauer, P. J. J.; van Spronsen, F. J.

2005-01-01

In a previous study, Dutch children with phenylketonuria (PKU) were found to be slightly shorter than their healthy counterparts. In the literature, it has been hypothesized that a higher protein intake is necessary to optimize growth in PKU patients. The study aimed to investigate whether protein

Event-related potential correlates of selective processing in early- and continuously-treated children with phenylketonuria : Effects of concurrent phenylalanine level and dietary control

NARCIS (Netherlands)

de Sonneville, Leo M. J.; Huijbregts, Stephan C. J.; van Spronsen, Francjan J.; Verkerk, Paul H.; Sergeant, Joseph A.; Licht, Robert

2010-01-01

This Study focused on important characteristics of attentional (selective) processing in children with early-treated phenylketonuria (PKU). Seven to 14-year-old children with PKU were allocated to high phenylalanine (Phe) and low Phe groups and compared with control children on amplitudes and

Event-related potential correlates of selective processing in early- and continuously-treated children with phenylketonuria: Effects of concurrent phenylalanine level and dietary control

NARCIS (Netherlands)

Sonneville, L.M.J. de; Huijbregts, S.C.J.; Spronsen, F.J. van; Verkerk, P.H.; Sergeant, J.A.; Licht, R.

2009-01-01

This study focused on important characteristics of attentional (selective) processing in children with early-treated phenylketonuria (PKU). Seven to 14-year-old children with PKU were allocated to high phenylalanine (Phe) and low Phe groups and compared with control children on amplitudes and

Sensory analysis of passion fruit cake with chocolate sauce for individuals with phenylketonuria

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Juliana dos Santos Vilar

2013-07-01

Full Text Available The aim of this study was to develop a recipe of passion fruit cake with chocolate syrup for individuals who have phenylketonuria and evaluate its acceptance. The samples were served to 50 untrained tasters and evaluated by the acceptability test using the nine point hedonic scale. Flavor was the most appreciated attribute by 66% of tasters. The cake had a mean of 7,0 corresponding to "liked moderately" in the hedonic scale and 94% of purchase intent. Therefore, the cake was accepted and would be purchased by the majority of participants.

Multiple origins for phenylketonuria in Europe

Energy Technology Data Exchange (ETDEWEB)

Eisensmith, R.C.; Okano, Y.; Dasovich, M.; Wang, T.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (United States)); Guettler, F.; Lou, H.; Guldberg, P. (John F. Kennedy Inst., Glostrup (Denmark)); Lichter-Konecki, U.; Konecki, D.S. (Universitaets-Kinderklinik, Heidelberg (Germany)); Svensson, E.; Hagenfeldt, L. (Huddinge University Hospital (Sweden)); Rey, F.; Munnich, A.; Lyonnet, S. (Hopital des Enfants-Malades, Paris (France)); Cockburn, F.; Connor, J.M. (Univ. of Glasgow (United Kingdom)); Pembrey, M.E.; Smith, I. (Univ. of London (United Kingdom)); Gitzelmann, R.; Steinmann, B. (Universitaets-Kinderklinik, Zuerich (Switzerland)); Apold, J.; Eiken, H.G. (Universitet i Bergen (Norway)); Giovannini, M.; Riva, E.; Longhi, R. (Universita Degli Studi Di Milano, Milan (Italy)); Romano, C.; Cerone, R. (Universita Di Genova, Genoa (Italy)); Naughten, E.R.; Mullins, C.; Cahalane, S. (Children' s Hospital, Dublin (Ireland)); Oezalp, I. (Hacettepe Univ., Ankara (Turkey))

1992-12-01

Phenylketonuria (PKU), a disorder of amino acid metabolism prevalent among Caucasians and other ethnic groups, is caused primarily by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). PKU is a highly heterogeneous disorder, with more than 60 molecular lesions identified in the PAH gene. The haplotype associations, relative frequencies, and distributions of five prevalent PAH mutations (R158Q, R261Q, IVS10nt546, R408W, and IVS12nt1) were established in a comprehensive European sample population and subsequently were examined to determine the potential roles of several genetic mechanisms in explaining the present distribution of the major PKU alleles. Each of these five mutations was strongly associated with only one of the more than 70 chromosomal haplotypes defined by eight RFLPs in or near the PAH gene. These findings suggest that each of these mutations arose through a single founding event that occurred within time periods ranging from several hundred to several thousand years ago. From the significant differences observed in the relative frequencies and distributions of these five alleles throughout Europe, four of these putative founding events could be localized to specific ethnic subgroups. Together, these data suggest that there were multiple, geographically and ethnically distinct origins for PKU within the European population. 63 refs., 2 figs., 3 tabs.

Costs and Outcomes over 36 Years of Patients with Phenylketonuria Who Do and Do Not Remain on a Phenylalanine-Restricted Diet

Science.gov (United States)

Guest, J. F.; Bai, J. J.; Taylor, R. R.; Sladkevicius, E.; Lee, P. J.; Lachmann, R. H.

2013-01-01

Background: To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. Methods: A computer-based model was constructed depicting the management of PKU patients over the first…

[Maternal and fetal outcomes with aortic dissection in pregnant patients with Marfan syndrome].

Science.gov (United States)

Yang, Puyu; Zhang, Jun; Li, Yanna; Wang, Hui; Zheng, Jun

2015-05-01

To evaluate the clinical characteristics of aortic dissection in pregnant patients with Marfan syndrome and the maternal and fetal outcomes in cardiovascular surgery. Seven pregnant women with Marfan syndrome with aortic dissection were identified, who were treated in Beijing Anzhen Hospital Affiliated to Capital Medical University between January 2012 and September 2014. Patient charts were reviewed for cardiovascular surgery, occurrence of complications, clinical features and the maternal and fetal outcomes. (1) Among 7 patients, 4 cases were diagnosed as type A aortic dissection and 3 were cases diagnosed as type B aortic dissection. The diagnosis mainly depends on CT angiography. New York Heart Association (NYHA) classify into 5 of level II, 1 of level III, 1 of leveI IV. Except for 1 patient with cardiac tamponade lead to heart failure, the remaining 6 cases had no complications. (2) Three patients underwent heart surgery with cardiopulmonary bypass in second trimester and two patients underwent heart surgery in third trimester. Two patients terminated pregnancy before heart surgery (one of whom underwent artificial abortion, one of whom underwent cesarean section in second trimester). (3) The methods of cardiovascular surgeries were as follow: 3 of Bentall+Sun', 1 of Bentall+Sun'+ right coronary artery bypass grafting, 1 of Bentall, 1 of the whole chest aorta replacement surgery, and 1 of femoral artery catheter chest aorta with membrane mesh stent implantation. The diameter of aortic roots measured during operation were 5 cm in 2 cases, 7 cm in 2 cases and 10 cm in 2 cases respectively. Among the 7 cases, 3 were conducted cesarean sections during cardiovascular surgery, 1 was terminated pregnancy due to intrauterine fetal death after cardiovascular surgery, and 1 was conducted cesarean section due to severe early-onset preeclampsia at 30 weeks of pregnancy after cardiovascular surgery. (4) Among the 7 cases, 3 were conducted cesarean sections during

Maternal and Perinatal Outcomes among Eclamptic Patients ...

African Journals Online (AJOL)

HP

1Department of Obstetrics and Gynaecology, Bugando Medical Centre, Mwanza, ... (10.5%), pulmonary oedema (10.5%), maternal stroke (8.8%), HELLP syndrome (50.9%), and Disseminated ..... health care services and medical attention.

Subacute onset leukodystrophy and visual-spatial disorders revealing phenylketonuria combined with homocysteinmia in adulthood: A case report.

Science.gov (United States)

Wang, Chunchen; Li, Jieying

2018-02-01

Phenylketonuria (PKU) is a metabolic disorder, which manifests a progressive irreversible neurological impairment during infancy and childhood. Hyperhomocysteinemia also showed that it might be involved in pathophysiology of many neuropsychiatric disorders. The late-onset clinical manifestations of these 2 diseases have not been reported elsewhere. We speculated that the late-onset PKU is caused by 2 kinds of metabolic dysfunction synergistically, especially a short period of irregular diet directly caused clinical symptoms. A 21-year old Asian male patient demonstrated subacute leukodystrophy and visual-spatial disorders of late onset in adulthood. Phenylketonuria combined with homocysteinmia, who presented with heterozygous mutations in gene encoding PAH p.G247R (c.739G>C) and p.Y204C (c.611A>G), along with homozygous mutation of gene encoding MTHFR c.677C>T. The patient was treated with cobalamine (500 μg/day), vitamin B6 (30 mg/day), folate (5 mg/day) and encouraged to follow a protein-restricted diet. Visual disorientation and cognitive function showed improvement. Head MR showed similar resolution with the original lesion. Serum homocysteine and folate analysis were normal with decreased phenylalanine level. This case suggests that neurological involvement of progressive nervous system dysfunction could be caused by more than one kind of inherited metabolic disturbances, and each one can induce or deteriorate the manifestations of another metabolic disorders.

Evaluating the Agreement of Risk Categorization for Fetal Down Syndrome Screening between Ultrasound-Based Gestational Age and Menstrual-Based Gestational Age by Maternal Serum Markers.

Science.gov (United States)

Chaksuwat, Pakorn; Sirichotiyakul, Supatra; Luewan, Suchaya; Tongsong, Theera

2018-01-01

To evaluate the agreement of risk categorization for Down syndrome screening between ultrasound scan-based gestational age (GA) and last menstrual period-based gestational age in both first and second trimesters by maternal serum markers. Data comprising 4,055 and 4,016 cases of first and second trimester screening were used. The maternal serum markers were analyzed using the ultrasound-based GA and menstrual age. The subjects whose menstrual age and ultrasound-based GA fell in different trimesters were excluded because the risk could not be calculated due to the different serum markers used in each trimester. The agreement of risk categorization for fetal Down syndrome was evaluated. The agreement of Down syndrome screening in the first and the second trimesters were 92.7% and 89%, respectively. The study found a good agreement of risk categorization by Kappa index, which was 0.615 for the overall screening. The menstrual age had a slight decrease in the detection rate and a lower false-positive rate. Menstrual age is acceptable in cases of accurate last menstrual period. However, in places where ultrasonography is not readily available, gestational age estimation by menstrual age along with clinical examination that corresponds to the gestational age can be reliable.

Congenital Malformations Associated with Maternal Diabetes

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Chih-Ping Chen

2005-03-01

Full Text Available Maternal diabetes has toxic effects on the development of the embryo and significantly increases the risk of congenital malformations in humans. The incidence of fetal structural defects caused by maternal pregestational diabetes is three- to fourfold higher than that caused by non-diabetic pregnancy. The congenital malformations associated with diabetic pregnancy arise before the seventh gestational week. Diabetic embryopathy can affect any developing organ system, including the central nervous system (CNS (anencephaly, spina bifida, microcephaly, and holoprosencephaly, skeletal system (caudal regression syndrome, sacral agenesis, and limb defects, renal system (renal agenesis, hydronephrosis, and ureteric abnormalities, cardiovascular system (transposition of the great vessels, ventricular septal defects, atrial septal defects, coarctation of the aorta, cardiomyopathy, and single umbilical artery, and gastrointestinal system (duodenal atresia, anorectal atresia, and small left colon syndrome. Pregnant women with fetuses with diabetic embryopathy may have chronic or unrecognized hyperglycemia and elevated levels of glycerated hemoglobin. This review emphasizes the necessity to consider hyperglycemia-induced teratogenesis during genetic counseling of parents with prenatally detected fetal malformations. Successful preconception counseling for women with diabetes mellitus and metabolic control will reduce birth defects and maternal morbidity.

Maternal MTHFR polymorphism (677 C-T) and risk of Down's syndrome child: meta-analysis.

Science.gov (United States)

Kaur, Amandeep; Kaur, Anupam

2016-09-01

Methylenetetrahydrofolate reductase (MTHFR) is the most important gene that participates in folate metabolism. Presence of valine instead of alanine at position 677 and elevated levels of homocystein causes DNA hypomethylation which in turn favours nondisjunction. In this study, we conducted a meta-analysis to establish link between maternal single-nucleotide polymorphism (SNP) and birth of Down's syndrome (DS) child. A total of 37 case-control studies were selected for analysis including our own, in which we investigated 110 cases and 111 control mothers. Overall, the result of meta-analysis showed significant risk of DS affected by the presence of maternal SNP (MTHFR 677 C-T OR = 0.816, 95% CI = 0.741-0.900, P <0.0001). Heterogeneity of high magnitude was observed among the studies. The chi-square value suggested a highly significant association between homozygous mutant TT genotype and birth of DS child (χ² = 23.63, P = 0.000). Genetic models suggested that 'T' allele possesses high risk for DS whether present in dominant (OR = 1.23, 95% CI = 1.13-1.34); codominant (OR = 1.17, 95% CI = 1.10-1.25) or recessive (OR = 1.21, 95% CI = 1.05-1.38) form. The analysis from all 37 studies combined together suggested that MTHFR 677 C-T is a major risk factor for DS birth.

Breastfeeding infants with phenylketonuria in the United States and Canada.

Science.gov (United States)

Banta-Wright, Sandra A; Press, Nancy; Knafl, Kathleen A; Steiner, Robert D; Houck, Gail M

2014-04-01

This study described the prevalence and duration of mothers' breastfeeding infants with phenylketonuria (PKU) and explored factors related to duration of breastfeeding as a surrogate for breastfeeding success. Descriptive analysis as performed from an international Internet survey of mothers (n=103) who met the inclusion criteria: (1) at least 21 years of age, (2) able to read and write in English, (3) child with PKU, and (4) living in the United States or Canada. Of the 103 mothers, 89 (86%) initiated breastfeeding immediately following delivery, whereas 14 (14%) chose bottle feeding. In comparison to breastfeeding after delivery, significantly fewer mothers breastfed after diagnosis (McNemar's χ(2)=30.33, pmothers' milk was associated with a shorter duration of breastfeeding among infants with PKU: χ(2) (42, n=73)=88.13, pmothers' breastfeeding infants with PKU to guide the development of interventions specific to these mothers to support their efforts to continue breastfeeding after the diagnosis of PKU.

Neurological assessment of 38 late-diagnosed children with classic phenylketonuria

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Zeliha Haytoglu

2016-03-01

Material and Methods: Thirty-eight late-diagnosed classic phenylketonuria patients were enrolled in the study. Plasma phenylalanine levels were measured by spectrofluorometric method. MRI was evaluated by a pediatric neuroradiologist. Ankara developmental screening inventory (ADSI and Wechsler intelligence scale for Turkish children (WISC-R test were performed to detect IQ scores. Porteus Mazo test adapted for Turkish children intelligence test were performed to all children. The EEG of all patients were recorded. VEP was used to measure the electrical activity in the brain to visual stimulus. Results: The high plasma phenylalanine levels and late-diagnosis were associated with low IQ scores, pathological EEG, and pathological VEP patterns. High PA levels were also associated with more serious white matter signal abnormalities. Conclusion: Our results demonstrated the impact of early diagnosis and low levels of phenylalanine at diagnosis on the intellectual, neurological development and visual outcomes. [Cukurova Med J 2016; 41(1.000: 21-27

Analysis of preventability of hypertensive disorder in pregnancy-related maternal death using the nationwide registration system of maternal deaths in Japan.

Science.gov (United States)

Katsuragi, Shinji; Tanaka, Hiroaki; Hasegawa, Junichi; Nakamura, Masamitsu; Kanayama, Naohiro; Nakata, Masahiko; Murakoshi, Takeshi; Yoshimatsu, Jun; Osato, Kazuhiro; Tanaka, Kayo; Sekizawa, Akihiko; Ishiwata, Isamu; Ikeda, Tomoaki

2018-04-26

Hypertensive disorder of pregnancy (HDP) is a major cause of maternal death. The goal of this study was to investigate factors associated with maternal death due to HDP. HDP-related maternal deaths in Japan reported to the Committee of the Ministry of Health, Labor and Welfare from 2010 to 2015 were examined. Out of 47 cases of HDP, 30 were identified as the major cause of maternal death. The median maternal age was 34 years (range 24-45) and the mortality in women aged ≥40 years was seven times higher that than in women aged deaths in Japan. Mothers aged ≥40 years are most at risk for HDP-related maternal death. Major concerns for preventabilities were late hospitalization, maternal transportation, and termination of pregnancy for term or near-term HDP. Regular vital checks and prompt lowering of BP were lacked during labor in most cases. HELLP syndrome should be managed at a general hospital with sufficient medical resources.

Maternal and Perinatal Outcomes among Eclamptic Patients ...

African Journals Online (AJOL)

, pulmonary oedema (10.5%), maternal stroke (8.8%), HELLP syndrome (50.9%), and Disseminated Intravascular Coagulopathy (3.5%). Perinatal deaths were caused by prematurity (42.9%) and birth asphyxia (57.1%). Forty-eight babies had ...

No evidence for pathogenic variants or maternal effect of ZFP57 as the cause of Beckwith-Wiedemann Syndrome

DEFF Research Database (Denmark)

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

2012-01-01

in patients with BWS. We sequenced ZFP57 in 27 BWS probands and in 23 available mothers to test for a maternal effect. We identified three novel, presumably benign sequence variants in ZFP57; thus, we found no evidence for ZFP57 alterations as a major cause in sporadic BWS cases.......Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome, which, in 50-60% of sporadic cases, is caused by hypomethylation of KCNQ1OT1 differentially methylated region (DMR) at chromosome 11p15.5. The underlying defect of this hypomethylation is largely unknown. Recently, recessive mutations...... of the ZFP57 gene were reported in patients with transient neonatal diabetes mellitus type 1, showing hypomethylation at multiple imprinted loci, including KCNQ1OT1 DMR in some. The aim of our study was to determine whether ZFP57 alterations were a genetic cause of the hypomethylation at KCNQ1OT1 DMR...

Phenylketonuria: Direct and indirect effects of phenylalanine.

Science.gov (United States)

Schlegel, Gudrun; Scholz, Ralf; Ullrich, Kurt; Santer, René; Rune, Gabriele M

2016-07-01

High phenylalanine concentrations in the brain due to dysfunctional phenylalanine hydroxylase (Pah) are considered to account for mental retardation in phenylketonuria (PKU). In this study, we treated hippocampal cultures with the amino acid in order to determine the role of elevated levels of phenylalanine in PKU-related mental retardation. Synapse density and dendritic length were dramatically reduced in hippocampal cultures treated with phenylalanine. Changes in cofilin expression and phosphorylation status, which were restored by NMDA, as well as reduced activation of the small GTPase Rac1, likely underlie these structural alterations. In the Pah(enu2) mouse, which carries a mutated Pah gene, we previously found higher synaptic density due to delayed synaptic pruning in response to insufficient microglia function. Microglia activity and C3 complement expression, both of which were reduced in the Pah(enu2) mouse, however, were unaffected in hippocampal cultures treated with phenylalanine. The lack of a direct effect of phenylalanine on microglia is the key to the opposite effects regarding synapse stability in vitro and in the Pah(enu2) mouse. Judging from our data, it appears that another player is required for the inactivation of microglia in the Pah(enu2) mouse, rather than high concentrations of phenylalanine alone. Altogether, the data underscore the necessity of a lifelong phenylalanine-restricted diet. Copyright © 2016 Elsevier Inc. All rights reserved.

Early Screening for Tetrahydrobiopterin Responsiveness in Phenylketonuria.

Science.gov (United States)

Porta, Francesco; Spada, Marco; Ponzone, Alberto

2017-08-01

Since 2007, synthetic tetrahydrobiopterin (BH4) has been approved as a therapeutic option in BH4-responsive phenylketonuria (PKU) and since 2015 extended to infants younger than 4 years in Europe. The current definition of BH4 responsiveness relies on the observation of a 20% to 30% blood phenylalanine (Phe) decrease after BH4 administration, under nonstandardized conditions. By this definition, however, patients with the same genotype or even the same patients were alternatively reported as responsive or nonresponsive to the cofactor. These inconsistencies are troubling, as frustrating patient expectations and impairing cost-effectiveness of BH4-therapy. Here we tried a quantitative procedure through the comparison of the outcome of a simple Phe and a combined Phe plus BH4 loading in a series of infants with PKU, most of them harboring genotypes already reported as BH4 responsive. Under these ideal conditions, blood Phe clearance did not significantly differ after the 2 types of loading, and a 20% to 30% decrease of blood Phe occurred irrespective of BH4 administration in milder forms of PKU. Such early screening for BH4 responsiveness, based on a quantitative assay, is essential for warranting an evidence-based and cost-effective therapy in those patients with PKU eventually but definitely diagnosed as responsive to the cofactor. Copyright © 2017 by the American Academy of Pediatrics.

Management strategy in pregnancies with elevated second-trimester maternal serum alpha-fetoprotein based on a second assay.

Science.gov (United States)

Spaggiari, Emmanuel; Ruas, Marie; Dreux, Sophie; Valat, Anne-Sylvie; Czerkiewicz, Isabelle; Guimiot, Fabien; Schmitz, Thomas; Delezoide, Anne-Lise; Muller, Françoise

2013-04-01

To assess maternal-fetal outcomes in pregnancies associated with persistently elevated second-trimester maternal serum alpha-fetoprotein. A retrospective cohort study in 658 patients with maternal serum alpha-fetoprotein ≥2.5 multiple of median, performed at routine Down syndrome screening. Maternal serum alpha-fetoprotein was assayed a second time in 341 of them. Outcomes were recorded in all cases. The group with unexplained maternal serum alpha-fetoprotein persistently ≥2.5 multiple of median was associated with more pregnancy complications 37 of 92 (40.2%) as fetal death, preeclampsia, intrauterine growth restriction, and congenital nephrotic syndrome, compared with the group with maternal serum alpha-fetoprotein that returned to a normal level 37 of 226 (16.4%) (P alpha-fetoprotein returns to a normal level on a second assay, the risk of adverse outcome significantly decreases, but these pregnancies are still at risk of complications and therefore need close surveillance. Repeat maternal serum alpha-fetoprotein assay allows identification of patients who should be offered amniocentesis to evaluate the risk of nephrotic syndrome and epidermolysis bullosa. Alpha-fetoprotein should be monitored in pregnancies associated with unexplained high maternal serum alpha-fetoprotein. A management strategy based on ultrasound examination, second maternal serum alpha-fetoprotein assay and amniocentesis is proposed to improve prenatal counseling and management of such pregnancies. However, a prospective study remains necessary to evaluate it. Copyright © 2013 Mosby, Inc. All rights reserved.

Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts.

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Predrag Novakovic

Full Text Available The pathogenesis of fetal death caused by porcine reproductive and respiratory syndrome virus (PRRSV remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n = 114 or sham inoculated (n = 19 at 85±1 days of gestation. Dams and their litters were humanely euthanized and necropsied 21 days later. PRRSV RNA concentration was measured by qRT-PCR in the maternal-fetal interface and fetal thymus (n = 1391. Presence of fetal lesions was positively related to PRRSV RNA concentration in the maternal-fetal interface and fetal thymus (P<0.05 for both, but not to the distribution or severity of vasculitis, or the severity of endometrial inflammation. The presence of fetal and umbilical lesions was associated with greater odds of meconium staining (P<0.05 for both. The distribution and severity of vasculitis in endometrium were not significantly related to PRRSV RNA concentration in maternal-fetal interface or fetal thymus. Endometrial inflammation severity was positively related to distribution and severity of vasculitis in endometrium (P<0.001 for both. Conclusions from this study suggest that type 2 PRRSV infection in pregnant gilts induces significant histopathological lesions at maternal-fetal interface, but they are not associated with presence of PRRSV in the maternal-fetal interface at 21 days post infection. Conversely, fetal pathological lesions are associated with presence of PRRSV in the maternal-fetal interface and fetal thymus, and meconium staining is significantly associated with the presence of both fetal and umbilical lesions observed 21 days post infection.

Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts

Science.gov (United States)

Novakovic, Predrag; Harding, John C. S.; Al-Dissi, Ahmad N.; Ladinig, Andrea; Detmer, Susan E.

2016-01-01

The pathogenesis of fetal death caused by porcine reproductive and respiratory syndrome virus (PRRSV) remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n = 114) or sham inoculated (n = 19) at 85±1 days of gestation. Dams and their litters were humanely euthanized and necropsied 21 days later. PRRSV RNA concentration was measured by qRT-PCR in the maternal-fetal interface and fetal thymus (n = 1391). Presence of fetal lesions was positively related to PRRSV RNA concentration in the maternal-fetal interface and fetal thymus (P<0.05 for both), but not to the distribution or severity of vasculitis, or the severity of endometrial inflammation. The presence of fetal and umbilical lesions was associated with greater odds of meconium staining (P<0.05 for both). The distribution and severity of vasculitis in endometrium were not significantly related to PRRSV RNA concentration in maternal-fetal interface or fetal thymus. Endometrial inflammation severity was positively related to distribution and severity of vasculitis in endometrium (P<0.001 for both). Conclusions from this study suggest that type 2 PRRSV infection in pregnant gilts induces significant histopathological lesions at maternal-fetal interface, but they are not associated with presence of PRRSV in the maternal-fetal interface at 21 days post infection. Conversely, fetal pathological lesions are associated with presence of PRRSV in the maternal-fetal interface and fetal thymus, and meconium staining is significantly associated with the presence of both fetal and umbilical lesions observed 21 days post infection. PMID:26963101

Consequences of low birth weight, maternal illiteracy and poor access to medical care in rural India: infantile iatrogenic Cushing syndrome

OpenAIRE

Karande, Sunil

2015-01-01

Home delivery, low birth weight babies and maternal illiteracy among the poor in rural India are frequent. The rural poor prefer to seek healthcare from private providers, most of whom have no formal medical training and buy medicines from private pharmacies without a prescription owing to a weakly regulated environment. This report is of a 4-month-old baby from a remote village in northern India, who presented with exogenous Cushing syndrome. This baby was a full-term low birth weight home d...

Phenylketonuria: translating research into novel therapies

Science.gov (United States)

Ho, Gladys

2014-01-01

Phenylketonuria (PKU) is an inborn error of metabolism of the amino acid phenylalanine. It is an autosomal recessive disorder with a rate of incidence of 1 in 10,000 in Caucasian populations. Mutations in the phenylalanine hydroxylase (PAH) gene are the major cause of PKU, due to the loss of the catalytic activity of the enzyme product PAH. Newborn screening for PKU allows early intervention, avoiding irreparable neurological damage and intellectual disability that would arise from untreated PKU. The current primary treatment of PKU is the limitation of dietary protein intake, which in the long term may be associated with poor compliance in some cases and other health problems due to malnutrition. The only alternative therapy currently approved is the supplementation of BH4, the requisite co-factor of PAH, in the orally-available form of sapropterin dihydrochloride. This treatment is not universally available, and is only effective for a proportion (estimated 30%) of PKU patients. Research into novel therapies for PKU has taken many different approaches to address the lack of PAH activity at the core of this disorder: enzyme replacement via virus-mediated gene transfer, transplantation of donor liver and recombinant PAH protein, enzyme substitution using phenylalanine ammonia lyase (PAL) to provide an alternative pathway for the metabolism of phenylalanine, and restoration of native PAH activity using chemical chaperones and nonsense read-through agents. It is hoped that continuing efforts into these studies will translate into a significant improvement in the physical outcome, as well as quality of life, for patients with PKU. PMID:26835324

Systematic Review and Meta-Analysis of Neuropsychiatric Symptoms and Executive Functioning in Adults With Phenylketonuria

Science.gov (United States)

Bilder, Deborah A.; Noel, J. Kay; Baker, Erin R.; Irish, William; Chen, Yinpu; Merilainen, Markus J.; Prasad, Suyash; Winslow, Barbara J.

2016-01-01

ABSTRACT This systematic review and meta-analysis (MA) investigates the impact of elevated blood phenylalanine (Phe) on neuropsychiatric symptoms in adults with phenylketonuria (PKU). The meta-analysis of PKU is challenging because high-quality evidence is lacking due to the limited number of affected individuals and few placebo-controlled, double-blind studies of adults with high and low blood Phe. Neuropsychiatric symptoms associated with PKU exceed general population estimates for inattention, hyperactivity, depression, and anxiety. High Phe is associated with an increased prevalence of neuropsychiatric symptoms and executive functioning deficits whereas low Phe is associated with improved neurological performance. Findings support lifelong maintenance of low blood Phe. PMID:27805419

Dietary Proteins, Developmental Programming, and Potential Implication in Maternal Obesity

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Alireza Jahan-mihan

2017-08-01

Full Text Available Background: Proteins are known mainly based on their metabolic and nutritional functions including protein synthesis and a source of energy. In spite of various physiological properties attributed to proteins, their functions have neither been addressed by assessing quality of proteins nor by nutrition and dietetic practices. Methods: Studies were included if they were randomized animal studies, clinical trials and systematic reviews/meta-analysis published in English language. Results: The effect of maternal diet in general and dietary proteins in particular during development on health of offspring has been well-studied. Protein content as well as source of protein in the diet consumed during pregnancy and lactation influenced the risk of metabolic syndrome characteristics in offspring. Both high and low protein diets showed detrimental effects on health of offspring. Moreover, comparison of maternal casein-based diet with soy protein-based diet showed more favorable effect on body weight, body composition, blood pressure, and glucose metabolism in offspring. However, the role of maternal dietary proteins in developing the risk of metabolic syndrome characteristics in offspring in gestational obesity is still unclear and needs further study. Conclusions: Dietary proteins are determining factors in developmental programming. Both quantity and source of proteins in maternal diet influenced the development of metabolic syndrome characteristics in offspring. However, whether they have the same function in presence of gestational obesity is still unclear and needs further study.

Crianças com fenilcetonúria: avaliação audiológica básica e supressão das otoemissões Children with phenylketonuria: basic audiological evaluation and suppression of otoacoustic emissions

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Patrícia Souza Ribeiro

2012-01-01

Full Text Available OBJETIVO: Avaliar a via auditiva de crianças com fenilcetonúria tratadas precocemente, por meio de audiometria, imitanciometria e supressão das emissões otoacústicas transientes. MÉTODOS:Estudo prospectivo transversal comparativo com amostra composta por 28 crianças, sendo 12 com fenilcetonúria e 16 sem a doença. Foi realizada a pesquisa dos limiares de audibilidade por via aérea e óssea, logoaudiometria, imitanciometria e supressão das emissões otoacústicas transientes. RESULTADOS: A audiometria e a logoaudiometria estiveram normais em todos os participantes. Foram encontrados piores resultados para o índice de reconhecimento de fala (IRF no grupo com fenilcetonúria. A imitanciometria revelou curva normal para todas as crianças, mas a pesquisa dos reflexos estapedianos demonstrou que as crianças do grupo com fenilcetonúria apresentaram aumento nos seus limiares nas frequências de 2 e 4 kHz. A supressão das emissões otoacústicas transientes não revelou diferença na comparação entre os grupos. CONCLUSÃO: A avaliação audiológica básica não identifica alterações na audição das crianças com fenilcetonúria, mas há pior discriminação ao IRF e aumento nos limiares de reflexos estapedianos nessas crianças, podendo indicar distúrbios do processamento auditivo. O estudo da supressão das otoemissões demonstra integridade do sistema eferente olivococlear medial nas crianças com fenilcetonúria.PURPOSE: To evaluate the auditory pathways of children with early-treated phenylketonuria through audiometry, immitance tests, and suppression of transient otoacoustic emissions. METHODS: Prospective cross-sectional study with sample composed by 28 children: 12 with phenylketonuria and 16 without the disease. Participants underwent auditory evaluations composed of air- and bone-conduction pure-tone audiometry, speech audiometry, immittance tests and suppression of transient otoacoustic emissions. RESULTS: All participants

Phenylketonuria mutation analysis in Northern Ireland: A rapid stepwise approach

Energy Technology Data Exchange (ETDEWEB)

Zschocke, J.; Graham, C.A.; Nevin, N.C. [Queen`s Univ., Belfast (Australia)] [and others

1995-12-01

We present a multistep approach for the rapid analysis of phenylketonuria (PKU) mutations. In the first step, three common mutations and a polymorphic short tandem repeat (STR) system are rapidly analyzed with a fluorescent multiplex assay. In the second step, minihaplotypes combining STR and VNTR data are used to determine rare mutations likely to be present in an investigated patient, which are then confirmed by restriction enzyme analysis. The remaining mutations are analyzed with denaturant gradient-gel electrophoresis and sequencing. The first two steps together identify both mutations in 90%-95% of PKU patients, and results can be obtained within 2 d. We have investigated 121 Northern Irish families with hyperphenylalaninemia, including virtually all patients born since 1972, and have found 34 different mutations on 241 of the 242 mutant alleles. Three mutations (R408W, 165T, and F39L) account for 57.5% of mutations, while 14 mutations occur with a frequency of 1%-6%. The present analysis system is efficient and inexpensive and is particularly well suited to routine mutation analysis in a diagnostic setting. 19 refs., 5 tabs.

Maternal and fetal insulin levels at birth in women with polycystic ovary syndrome: data from a randomized controlled study on metformin.

Science.gov (United States)

Helseth, Ragnhild; Vanky, Eszter; Stridsklev, Solhild; Vogt, Christina; Carlsen, Sven M

2014-05-01

Metformin is suggested to reduce pregnancy complications in women with polycystic ovary syndrome (PCOS). Metformin crosses the placenta and therapeutic concentrations are measured in the fetal circulation. Whether metformin treatment in pregnant PCOS women affects maternal and fetal insulin concentrations at birth is not clarified. To investigate the possible effect of metformin on insulin concentrations in umbilical cord blood and the possible association between maternal and fetal insulin concentrations. Post-hoc analysis of a subgroup of PCOS women participating in a double-blind randomized controlled trial. University hospital setting. Women with PCOS (n=118), aged 19-39 years. Maternal and umbilical cord insulin concentrations immediately after birth. At delivery women randomized to metformin had lower insulin concentrations than those randomized to placebo (259±209 vs 361±261 pmol/l; P=0.020). No difference was found in insulin concentrations in umbilical venous (P=0.95) and arterial (P=0.39) blood between the metformin and placebo groups. The arteriovenous difference was also equal between the groups (P=0.38). Insulin concentrations were higher in the umbilical vein than in the umbilical artery independent of randomization (70±51 vs 45±48 pmol/l; Pmetformin treatment during pregnancy resulted in lower maternal insulin concentrations at delivery. Metformin treatment did not affect fetal insulin concentrations. Higher insulin concentrations in the umbilical vein indicate that the placenta somehow secretes insulin to the fetus. The possibility of placental insulin secretion to the fetus deserves further investigations.

Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (IV

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2008-06-01

Full Text Available Fetuses with neural tube defects (NTDs may be associated with maternal and fetal risk factors. This article provides a comprehensive review of maternal and fetal risk factors associated with NTDs, such as infertility, periconceptional clomiphene use and assisted reproductive technology, periconceptional folic acid deficiency and effects offolic acid supplementation and fortification on NTD rates, periconceptional vitamin B1 2 deficiency, single nucleotide polymorphisms and polymorphisms in genes of folate metabolism, and maternal autoantibodies to folate receptors. NTDs associated with maternal and fetal risk factors are an important cause of NTDs. Perinatal identification of NTDs should alert the clinician to the maternal and fetal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling. [Taiwan J Obstet Cynecol 2008;47(2:141-1 50

Maternal risk factors for fetal alcohol syndrome and partial fetal alcohol syndrome in South Africa: a third study.

Science.gov (United States)

May, Philip A; Gossage, J Phillip; Marais, Anna-Susan; Hendricks, Loretta S; Snell, Cudore L; Tabachnick, Barbara G; Stellavato, Chandra; Buckley, David G; Brooke, Lesley E; Viljoen, Denis L

2008-05-01

This is a third exploration of risk factors for the two most severe forms of fetal alcohol spectrum disorders (FASD), fetal alcohol syndrome (FAS) and Partial FAS (PFAS), in a South African community with the highest reported prevalence of FAS in the world. In a case control design, interview and collateral data concerning mothers of 72 first grade children with FAS or PFAS are compared with 134 randomly selected maternal controls of children from the same schools. Significant differences were found between the mothers of FASD children and controls in socio-economic status, educational attainment, and a higher prevalence of FASD among rural residents. The birth order of the index children, gravidity, and still birth were significantly higher among mothers of FASD children. Mothers of children with a FASD are less likely to be married and more likely to have a male partner who drank during the index pregnancy. Current and gestational alcohol use by mothers of FASD children is bingeing on weekends, with no reduction in drinking reported in any trimester in 75 to 90% of the pregnancies that resulted in an FAS child or during 50 to 87% of PFAS-producing pregnancies. There was significantly less drinking among the controls in the second and third trimesters (11 to 14%). Estimated peak blood alcohol concentrations (BAC)s of the mothers of PFAS children range from 0.155 in the first trimester to 0.102 in the third, and for mothers of FAS children the range is from 0.197 to 0.200 to 0.191 in the first, second, and third. Smoking percentage during pregnancy was significantly higher for mothers of FASD children (82 to 84%) than controls (35%); but average quantity smoked is low in the 3 groups at 30 to 41 cigarettes per week. A relatively young average age of the mother at the time of FAS and PFAS births (28.8 and 24.8 years respectively) is not explained by early onset of regular drinking (mean = 20.3 to 20.5 years of age). But the mean years of alcohol consumption is

ANALYSIS OF FREQUENCY OF PHENYLKETONURIA AMONG INSTITUTIONALIZED

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S VALIAN

2003-09-01

Full Text Available Introduction: Phenylketonuria (PKU is a genetic disease, which is caused by deficiency in phenylalanine hydroxylase (PAH enzyme. Untreated patients will develop a severe mental retardation, which is irreversible. In this study, the incidence of the PKU disease among isolated mentally retarded residents in institutions in Isfahan, was investigated. Methods: A total number of 1541 patients were involved in the study. Of the patients studied, 611 with no known reason for their mental retardation were chosen for blood sampling. Blood samples were collected on filter papers and examined by Gutheri bacterial inhibition assay (GBIA, which is specific for PKU In patients with positive test, the serum phenylalanine was quatitavely analyzed using high pressure liquid chromatography, HPLC. Results: Among the patients examined, 33 were found positive. Quantitative analysis of phenylalanine allowed classification of the patients, indicating 600 with classical, 36% with moderate, and 3% with mild type of PKU Furthermore; it was found that in 68% of the cases, parents are third grade relative. Discussion: The results obtained in this screening study indicated that 2.1% of the patients in the institutions for mentally related in Isfahan suffered from PKU The incidence of the disease is relatively high compare to the reports from other countries. Since, a large number of patients (68% are the results of consanguineous marriages, this kind of marriage could be considered as one of the important factors involved in the prevalence of PKU in Isfahan.

Pregnancy outcome in joint hypermobility syndrome and Ehlers-Danlos syndrome.

Science.gov (United States)

Sundelin, Heléne E K; Stephansson, Olof; Johansson, Kari; Ludvigsson, Jonas F

2017-01-01

An increased risk of preterm birth in women with joint hypermobility syndrome or Ehlers-Danlos syndrome is suspected. In this nationwide cohort study from 1997 through 2011, women with either joint hypermobility syndrome or Ehlers-Danlos syndrome or both disorders were identified through the Swedish Patient Register, and linked to the Medical Birth Register. Thereby, 314 singleton births to women with joint hypermobility syndrome/Ehlers-Danlos syndrome before delivery were identified. These births were compared with 1 247 864 singleton births to women without a diagnosis of joint hypermobility syndrome/Ehlers-Danlos syndrome. We used logistic regression, adjusted for maternal age, smoking, parity, and year of birth, to calculate adjusted odds ratios for adverse pregnancy outcomes. Maternal joint hypermobility syndrome/Ehlers-Danlos syndrome was not associated with any of our outcomes: preterm birth (adjusted odds ratio = 0.6, 95% confidence interval 0.3-1.2), preterm premature rupture of membranes (adjusted odds ratio = 0.8; 95% confidence interval 0.3-2.2), cesarean section (adjusted odds ratio = 0.9, 95% confidence interval 0.7-1.2), stillbirth (adjusted odds ratio = 1.1, 95% confidence interval 0.2-7.9), low Apgar score (adjusted odds ratio = 1.6, 95% confidence interval 0.7-3.6), small for gestational age (adjusted odds ratio = 0.9, 95% confidence interval 0.4-1.8) or large for gestational age (adjusted odds ratio = 1.2, 95% confidence interval 0.6-2.1). Examining only women with Ehlers-Danlos syndrome (n = 62), we found a higher risk of induction of labor (adjusted odds ratio = 2.6; 95% confidence interval 1.4-4.6) and amniotomy (adjusted odds ratio = 3.8; 95% confidence interval 2.0-7.1). No excess risks for adverse pregnancy outcome were seen in joint hypermobility syndrome. Women with joint hypermobility syndrome/Ehlers-Danlos syndrome do not seem to be at increased risk of adverse pregnancy outcome. © 2016 Nordic Federation of

Association between pre- and perinatal exposures and Tourette syndrome or chronic tic disorder in the ALSPAC cohort.

Science.gov (United States)

Mathews, Carol A; Scharf, Jeremiah M; Miller, Laura L; Macdonald-Wallis, Corrie; Lawlor, Debbie A; Ben-Shlomo, Yoav

2014-01-01

Tourette syndrome and chronic tic disorder are heritable but aetiologically complex. Although environment plays a role in their development, existing studies of non-genetic risk factors are inconsistent. To examine the association between pre- and perinatal exposures and Tourette syndrome/chronic tic disorder in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective longitudinal pre-birth cohort. Relationships between exposures and Tourette syndrome/chronic tic disorder were examined in 6090 children using logistic regression. Maternal alcohol and cannabis use, inadequate maternal weight gain and parity were associated with Tourette syndrome or Tourette syndrome/chronic tic disorder. Other previously reported exposures, including birth weight and prenatal maternal smoking, were not associated with Tourette syndrome/chronic tic disorder. This study supports previously reported relationships between Tourette syndrome/chronic tic disorder and prenatal alcohol exposure, and identifies additional previously unexplored potential prenatal risk factors.

Clinical teratology

International Nuclear Information System (INIS)

McCormack, M.K.

1983-01-01

Of particular importance in teratogenesis is the time of exposure to the offending environmental agent, route of exposure, and genotype of the embryo and the mother. The major teratogens include irradiation, maternal infections, other illnesses in pregnancy (diabetes, thyroid disease, maternal phenylketonuria, virilizing diseases), a host of pharmacologic agents and environmental contaminants. Teratogen exposure carries the potential for cancer in later life. Several sources of information on teratogens are now available

Clinical teratology

Energy Technology Data Exchange (ETDEWEB)

McCormack, M.K.

1983-12-01

Of particular importance in teratogenesis is the time of exposure to the offending environmental agent, route of exposure, and genotype of the embryo and the mother. The major teratogens include irradiation, maternal infections, other illnesses in pregnancy (diabetes, thyroid disease, maternal phenylketonuria, virilizing diseases), a host of pharmacologic agents and environmental contaminants. Teratogen exposure carries the potential for cancer in later life. Several sources of information on teratogens are now available.

Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring

NARCIS (Netherlands)

Pruis, M. G. M.; Lendvai, A.; Bloks, V. W.; Zwier, M. V.; Baller, J. F. W.; de Bruin, A.; Groen, A. K.; Plosch, T.

AimMetabolic programming via components of the maternal diet during gestation may play a role in the development of different aspects of the metabolic syndrome. Using a mouse model, we aimed to characterize the role of maternal western-type diet in the development of non-alcoholic fatty liver

Current thoughts on maternal nutrition and fetal programming of the metabolic syndrome.

Science.gov (United States)

Brenseke, Bonnie; Prater, M Renee; Bahamonde, Javiera; Gutierrez, J Claudio

2013-01-01

Chronic diseases such as type 2 diabetes and cardiovascular disease are the leading cause of death and disability worldwide. Although the metabolic syndrome has been defined in various ways, the ultimate importance of recognizing this combination of disorders is that it helps identify individuals at high risk for both type 2 diabetes and cardiovascular disease. Evidence from observational and experimental studies links adverse exposures in early life, particularly relating to nutrition, to chronic disease susceptibility in adulthood. Such studies provide the foundation and framework for the relatively new field of developmental origins of health and disease (DOHaD). Although great strides have been made in identifying the putative concepts and mechanisms relating specific exposures in early life to the risk of developing chronic diseases in adulthood, a complete picture remains obscure. To date, the main focus of the field has been on perinatal undernutrition and specific nutrient deficiencies; however, the current global health crisis of overweight and obesity demands that perinatal overnutrition and specific nutrient excesses be examined. This paper assembles current thoughts on the concepts and mechanisms behind the DOHaD as they relate to maternal nutrition, and highlights specific contributions made by macro- and micronutrients.

Programming social behavior by the maternal fragile X protein.

Science.gov (United States)

Zupan, B; Sharma, A; Frazier, A; Klein, S; Toth, M

2016-07-01

The developing fetus and neonate are highly sensitive to maternal environment. Besides the well-documented effects of maternal stress, nutrition and infections, maternal mutations, by altering the fetal, perinatal and/or early postnatal environment, can impact the behavior of genetically normal offspring. Mutation/premutation in the X-linked FMR1 (encoding the translational regulator FMRP) in females, although primarily responsible for causing fragile X syndrome (FXS) in their children, may also elicit such maternal effects. We showed that a deficit in maternal FMRP in mice results in hyperactivity in the genetically normal offspring. To test if maternal FMRP has a broader intergenerational effect, we measured social behavior, a core dimension of neurodevelopmental disorders, in offspring of FMRP-deficient dams. We found that male offspring of Fmr1(+/-) mothers, independent of their own Fmr1 genotype, exhibit increased approach and reduced avoidance toward conspecific strangers, reminiscent of 'indiscriminate friendliness' or the lack of stranger anxiety, diagnosed in neglected children and in patients with Asperger's and Williams syndrome. Furthermore, social interaction failed to activate mesolimbic/amygdala regions, encoding social aversion, in these mice, providing a neurobiological basis for the behavioral abnormality. This work identifies a novel role for FMRP that extends its function beyond the well-established genetic function into intergenerational non-genetic inheritance/programming of social behavior and the corresponding neuronal circuit. As FXS premutation and some psychiatric conditions that can be associated with reduced FMRP expression are more prevalent in mothers than full FMR1 mutation, our findings potentially broaden the significance of FMRP-dependent programming of social behavior beyond the FXS population. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

A familial Cri-du-Chat/5p deletion syndrome resulted from rare maternal complex chromosomal rearrangements (CCRs and/or possible chromosome 5p chromothripsis.

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Heng Gu

Full Text Available Cri-du-Chat syndrome (MIM 123450 is a chromosomal syndrome characterized by the characteristic features, including cat-like cry and chromosome 5p deletions. We report a family with five individuals showing chromosomal rearrangements involving 5p, resulting from rare maternal complex chromosomal rearrangements (CCRs, diagnosed post- and pre-natally by comprehensive molecular and cytogenetic analyses. Two probands, including a 4½-year-old brother and his 2½-year- old sister, showed no diagnostic cat cry during infancy, but presented with developmental delay, dysmorphic and autistic features. Both patients had an interstitial deletion del(5(p13.3p15.33 spanning ≈ 26.22 Mb. The phenotypically normal mother had de novo CCRs involving 11 breakpoints and three chromosomes: ins(11;5 (q23;p14.1p15.31,ins(21;5(q21;p13.3p14.1,ins(21;5(q21;p15.31p15.33,inv(7(p22q32dn. In addition to these two children, she had three first-trimester miscarriages, two terminations due to the identification of the 5p deletion and one delivery of a phenotypically normal daughter. The unaffected daughter had the maternal ins(11;5 identified prenatally and an identical maternal allele haplotype of 5p. Array CGH did not detect any copy number changes in the mother, and revealed three interstitial deletions within 5p15.33-p13.3, in the unaffected daughter, likely products of the maternal insertions ins(21;5. Chromothripsis has been recently reported as a mechanism drives germline CCRs in pediatric patients with congenital defects. We postulate that the unique CCRs in the phenotypically normal mother could resulted from chromosome 5p chromothripsis, that further resulted in the interstitial 5p deletions in the unaffected daughter. Further high resolution sequencing based analysis is needed to determine whether chromothripsis is also present as a germline structural variation in phenotypically normal individuals in this family.

Association between pre- and perinatal exposures and Tourette syndrome or chronic tic disorder in the ALSPAC cohort†

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Mathews, Carol A.; Scharf, Jeremiah M.; Miller, Laura L.; Macdonald-Wallis, Corrie; Lawlor, Debbie A.; Ben-Shlomo, Yoav

2014-01-01

Background Tourette syndrome and chronic tic disorder are heritable but aetiologically complex. Although environment plays a role in their development, existing studies of non-genetic risk factors are inconsistent. Aims To examine the association between pre- and perinatal exposures and Tourette syndrome/chronic tic disorder in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective longitudinal pre-birth cohort. Method Relationships between exposures and Tourette syndrome/chronic tic disorder were examined in 6090 children using logistic regression. Results Maternal alcohol and cannabis use, inadequate maternal weight gain and parity were associated with Tourette syndrome or Tourette syndrome/chronic tic disorder. Other previously reported exposures, including birth weight and prenatal maternal smoking, were not associated with Tourette syndrome/chronic tic disorder. Conclusions This study supports previously reported relationships between Tourette syndrome/chronic tic disorder and prenatal alcohol exposure, and identifies additional previously unexplored potential prenatal risk factors. PMID:24262815

Congenital varicella syndrome: cranial MRI in a long-term survivor

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Deasy, N.P.; Jarosz, J.M.; Cox, T.C.S.; Hughes, E.

1999-01-01

Congenital varicella syndrome is a rare disorder which follows maternal infection in the first or early second trimester. The syndrome comprises a number of malformations including microcephaly, cortical destruction and limb hypoplasia. We describe a case where there has been long-term survival following second trimester maternal infection. The clinical findings, including the characteristic lower limb hypoplasia, are documented, as are the appearances on cranial MRI indicating an encephaloclastic porencephaly. (orig.) (orig.)

78 FR 54255 - Single-Case Deviation From Competition Requirements: Maternal and Child Health (MCH) Bureau's...

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2013-09-03

... Deviation From Competition Requirements: Maternal and Child Health (MCH) Bureau's Research Network on... practice over time (e.g., Preterm birth, Diabetes during pregnancy, Obesity, Nausea and vomiting of... disorders during pregnancy, Down syndrome); Studies that assess the maternal-child health workforce (e.g...

Salivary serotonin does not correlate with central serotonin turnover in adult phenylketonuria (PKU patients

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Joseph Leung

2018-06-01

Full Text Available Introduction: Phenylketonuria (PKU is an inborn error of metabolism associated with an increased risk of behavioural and mood disorders. There are currently no reliable markers for monitoring mood in PKU. The purpose of this study was to evaluate salivary serotonin as a possible non-invasive marker of long-term mood symptoms and central serotonin activity in patients with PKU. Methods: 20 patients were recruited from our Adult Metabolic Diseases Clinic. Age, sex, plasma phenylalanine (Phe level, DASS (Depression Anxiety Stress Scales depression score, DASS anxiety score, BMI, salivary serotonin, salivary cortisol, 2-year average Phe, 2-year average tyrosine (Tyr, and 2-year average Phe:Tyr ratio were collected for each patient. Spearman's ρ correlation analysis was used to determine if there was any relationship between any of the parameters. Results: There were positive correlations between DASS anxiety and DASS depression scores (Spearman's ρ = 0.8708, p-value < 0.0001, BMI and plasma Phe level (Spearman's ρ = 0.6228, p-value = .0034, and 2-year average Phe and BMI (Spearman's ρ = 0.5448, p-value = .0130. There was also a negative correlation between salivary cortisol and plasma Phe level (Spearman's ρ = −0.5018, p-value = .0338. All other correlations were not statistically significant. Conclusion: Salivary serotonin does not correlate with peripheral phenylalanine levels, DASS depression scale scores, or DASS anxiety scale scores, implying that salivary serotonin does not reflect central serotonin turnover. Additionally, this study suggests that salivary serotonin is not a suitable marker for monitoring dietary control, mood, or anxiety in PKU. Synopsis: Salivary serotonin does not correlate with peripheral phenylalanine levels, DASS depression scale scores, or DASS anxiety scale scores, suggesting that salivary serotonin is not a suitable marker for monitoring dietary control, mood, or anxiety in PKU

[Maternal deaths due to infectious cause, results from the French confidential enquiry into maternal deaths, 2010-2012].

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Rigouzzo, A; Tessier, V; Zieleskiewicz, L

2017-12-01

Over the period 2010-2012, maternal mortality from infectious causes accounted for 5% of maternal deaths by direct causes and 16% of maternal deaths by indirect causes. Among the 22 deaths caused by infection occurred during this period, 6 deaths were attributed to direct causes from genital tract origin, confirming thus the decrease in direct maternal deaths by infection during the last ten years. On the contrary, indirect maternal deaths by infection, from extragenital origin, doubled during the same period, with 16 deaths in the last triennium, dominated by winter respiratory infections, particularly influenza: the 2009-2010 influenza A (H1N1) virus pandemic was the leading cause of indirect maternal mortality by infection during the studied period. The main infectious agents involved in maternal deaths from direct causes were Streptococcus A, Escherichia Coli and Clostridium perfringens: these bacterias were responsible for toxic shock syndrome, severe sepsis, secondary in some cases to cellulitis or necrotizing fasciitis. Of the 6 deaths due to direct infection, 4 were considered avoidable because of inadequate management: delayed or missed diagnosis, delayed or inadequate initiation of a specific medical and/or surgical treatment. Of the 16 indirect maternal deaths due to infection causes, the most often involved infectious agents were influenza A (H1N1) virus and Streptococcus pneumonia with induced purpura fulminans: the absence of influenza vaccination during pregnancy, delayed diagnosis and emergency initiation of a specific treatment, were the main contributory factors to these deaths and their avoidability in 70% of the cases analyzed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Analog kefir production with a low phenylalanine for Phenylketonuria

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Amir Yari

2017-06-01

Full Text Available Phenylketonuria (PKU is one of the most prevalent types of hereditary metabolic disorders which is caused due to an absence or reduction of the activity of the Phenylalanine hydroxylase enzyme in the liver which in turn, inhibits the transformation of phenylalanine (Phe to tyrosine. In clinical terms, this disorder is displayed with severe, permanent and irreversible mental retardation. This research was aimed at development of a highly nutrient and acceptable suitable analogue Kefir drink for these patients. The mentioned drink is based on milk permeate, cream powder and includes glycomacropeptide (GMP as a source of protein, starter as a fermentation source, the trance glutamines (TG enzyme, dough stabilizer and modified corn starch as tissue maker, salt and water. The GMP used in this analogue drink is intended for enrichment of the product and therefore it was added by 3% to one formula. The aforementioned sample had a lower calculated amount of pH and alcohol percentage in comparison with the 16 samples which did not have GMP. The results of this study showed that the analog kefir has a low level of phenylalanine (30.40 mg/100g and in that regard, it can be considered to be useful for patients with PKU.

Cushing's syndrome in pregnancy.

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Nassi, Rossella; Ladu, Cristina; Vezzosi, Chiara; Mannelli, Massimo

2015-02-01

Cushing's syndrome is a rare condition in the general population and is even less common during pregnancy with only a few cases reported in literature. The diagnosis of Cushing's syndrome may be difficult during pregnancy because the typical features of the disorder and pregnancy may overlap. However, Cushing's syndrome results in increased fetal and maternal complications, and diagnosis and treatment are critical. This report describes a case of 26-year-old female at the 19th week of pregnancy with symptoms and signs of hypercortisolism, where ACTH-independent Cushing's syndrome was diagnosed and treated by robotic laparoscopic adrenalectomy at the 21th week of gestation.

Breast-feeding success among infants with phenylketonuria.

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Banta-Wright, Sandra A; Shelton, Kathleen C; Lowe, Nancy D; Knafl, Kathleen A; Houck, Gail M

2012-08-01

Breast milk is the nutrition of choice for human infants (American Academy of Pediatrics, 2005; American Association of Family Physicians, 2008; Association of Women's Health Obstetric and Neonatal Nurses, 2005; Canadian Paediatric Society, 2005; U.S. Preventive Services Task Force, 2008; World Health Organization, 2009). In comparison to standard commercial formula, human breast milk has a lower concentration of protein and a lower content of the amino acid phenylalanine (Phe). For infants with phenylketonuria (PKU), these attributes of human breast milk make it ideal as a base source of nutrition. The purpose of this study was to compare the incidence and duration of breast-feeding and corresponding Phe levels of breast-fed and formula-fed infants with PKU in the caseload of a pediatric metabolic clinic at an urban tertiary-care medical center. Charts were reviewed for infants diagnosed with PKU beginning with 2005 and ending with 1980, the year no further breast-feeding cases were identified in the PKU population. During the first year of life, most of the infants, whether breast-fed or formula-fed, had similar mean Phe levels. However, the frequency distributions revealed that more breast-fed infants with PKU had Phe levels within the normal range (120-360 μmol/L) and were less likely to have low Phe levels (<120 μmol/L) than formula-fed infants with PKU. Further research is needed to understand how mothers manage breast-feeding in the context of PKU. Copyright © 2012 Elsevier Inc. All rights reserved.

Language processing and executive functions in early treated adults with phenylketonuria (PKU).

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De Felice, Sara; Romani, Cristina; Geberhiwot, Tarekegn; MacDonald, Anita; Palermo, Liana

We provide an in-depth analysis of language functions in early-treated adults with phenylketonuria (AwPKUs, N = 15-33), as compared to age- and education-matched controls (N = 24-32; N varying across tasks), through: a. narrative production (the Cinderella story), b. language pragmatics comprehension (humour, metaphors, inferred meaning), c. prosody discrimination d. lexical inhibitory control and planning (Blocked Cyclic Naming; Hayling Sentence Completion Test, Burgess & Shallice, 1997). AwPKUs exhibited intact basic language processing (lexical retrieval, phonology/articulation, sentence construction). Instead, deficits emerged in planning and reasoning abilities. Compared to controls, AwPKUs were: less informative in narrative production (lower rate of Correct Information Units); slower in metaphorical understanding and inferred meaning; less accurate in focused lexical-search (Hayling test). These results suggest that i) executive deficits in PKU cannot be explained by an accumulation of lower-order deficits and/or general speed impairments, ii) executive functions engage dedicated neurophysiological resources, rather than simply being an emergent property of lower-level systems.

Molecular mechanisms of maternal vascular dysfunction in preeclampsia.

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Goulopoulou, Styliani; Davidge, Sandra T

2015-02-01

In preeclampsia, as a heterogeneous syndrome, multiple pathways have been proposed for both the causal as well as the perpetuating factors leading to maternal vascular dysfunction. Postulated mechanisms include imbalance in the bioavailability and activity of endothelium-derived contracting and relaxing factors and oxidative stress. Studies have shown that placenta-derived factors [antiangiogenic factors, microparticles (MPs), cell-free nucleic acids] are released into the maternal circulation and act on the vascular wall to modify the secretory capacity of endothelial cells and alter the responsiveness of vascular smooth muscle cells to constricting and relaxing stimuli. These molecules signal their deleterious effects on the maternal vascular wall via pathways that provide the molecular basis for novel and effective therapeutic interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Parent-of-origin effects in Turner Syndrome patients

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Wang, Jada; Styers, Marshall; Sayres, Melissa Wilson

2015-01-01

Turner Syndrome patients have a single X chromosome, without a partner, X or Y. It has been suggested that the inheritance of the maternal X or paternal X may affect the severity of Turner Syndrome, as well as the incidence of mental disorders in Turner Syndrome individuals. Parental imprinting on the X chromosome may lead to different phenotypic variations in Turner Syndrome patients. In this project, we conduct an analysis of the current state of research on Turner Syndrome, and review the ...

Current Thoughts on Maternal Nutrition and Fetal Programming of the Metabolic Syndrome

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Bonnie Brenseke

2013-01-01

Full Text Available Chronic diseases such as type 2 diabetes and cardiovascular disease are the leading cause of death and disability worldwide. Although the metabolic syndrome has been defined in various ways, the ultimate importance of recognizing this combination of disorders is that it helps identify individuals at high risk for both type 2 diabetes and cardiovascular disease. Evidence from observational and experimental studies links adverse exposures in early life, particularly relating to nutrition, to chronic disease susceptibility in adulthood. Such studies provide the foundation and framework for the relatively new field of developmental origins of health and disease (DOHaD. Although great strides have been made in identifying the putative concepts and mechanisms relating specific exposures in early life to the risk of developing chronic diseases in adulthood, a complete picture remains obscure. To date, the main focus of the field has been on perinatal undernutrition and specific nutrient deficiencies; however, the current global health crisis of overweight and obesity demands that perinatal overnutrition and specific nutrient excesses be examined. This paper assembles current thoughts on the concepts and mechanisms behind the DOHaD as they relate to maternal nutrition, and highlights specific contributions made by macro- and micronutrients.

Ketonuria and HELLP syndrome.

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Gubbala, Phanendra Kumar; Karoshi, Mahantesh; Zakaria, Faris

2009-01-01

We recently managed a patient with the HELLP syndrome (Haemolysis, Elevated Liver enzymes and Low Platelet count) where there was a delay in diagnosis due to gastroenteritis. This case also reiterates the varied or lack of symptomatology in patients developing HELLP and obscuring the initial diagnosis. Patients with HELLP syndrome have significant maternal morbidity and mortality, hence clinical vigilance and high suspicion play a key role in the diagnosis and subsequent management.

Phenylketonuria is not a risk factor for changes of inflammation status as assessed by interleukin 6 and interleukin 8 concentrations.

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Mozrzymas, Renata; Duś-Żuchowska, Monika; Kałużny, Łukasz; Wenska-Chyży, Ewa; Walkowiak, Jarosław

2016-01-01

High oxidative stress and a reduced potential for free radical scavenging in phenylketonuria (PKU) patients, a phenomenon confirmed in a few studies, may lead to systemic chronic inflammation. The aim of this study was to compare the inflammation status, as assessed by interleukin 6 and interleukin 8 concentrations, in patients with PKU and in healthy controls. Twenty patients with classical PKU, aged 18-34 years and under dietary control, were enrolled in the study. The control group comprised of 20 healthy subjects matched for age and sex. Interleukin 6 and 8 levels were measured by enzyme-linked immunosorbent assay (ELISA) kits in all study participants. IL-6 concentrations in the study group ranged from 0.74 pg/ml to 1.34 pg/ml. No significant differences were found between IL-6 concentration between the study group and the control group (p = 0.989). IL-8 concentrations ranged from 17.56 pg/ml to 20.87 pg/ml. The obtained results of IL-8 levels did not differ significantly between the study group and control group (p = 0.192). No significant correlation was observed between Phe blood levels and IL-6 or IL-8 concentrations in the study group (ρ respectively: -0.225, 0.177). In a multivariate analysis, neither IL-6 nor IL-8 concentrations were correlated with sex, age, BMI and Phe levels. Phenylketonuria is not a risk factor for changes of inflammation status as assessed by IL-6 and IL-8 concentrations.

Adult phenylketonuria presenting with subacute severe neurologic symptoms.

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Seki, M; Takizawa, T; Suzuki, S; Shimizu, T; Shibata, H; Ishii, T; Hasegawa, T; Suzuki, N

2015-08-01

We report a 48-year-old Japanese woman with phenylketonuria (PKU) who presented with severe neurological symptoms more than 30 years after discontinuation of dietary treatment. She was diagnosed with PKU at 6-years-old and was treated with a phenylalanine restricted diet until she was 15 years old. When she was 48-years-old she started having difficulty walking. After several months, she presented with severe disturbance of consciousness and was admitted. She was diagnosed as having neurological complications associated with PKU. We observed temporal changes in her laboratory data, brain MRI and single-photon emission computed tomography (SPECT) scan findings. Brain MRI on T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted images revealed high intensity lesions in her bilateral frontal lobes and 123I-IMP SPECT showed marked and diffuse hypoperfusion in the bilateral cerebrum and cerebellum. After the resumption of dietary treatment, serum phenylalanine concentrations immediately decreased to the normal range. However, her neurological symptoms took longer to improve. We also found no clear temporal association between MRI findings and clinical severity. SPECT abnormalities showed marked improvement after treatment. It is well known that PKU patients who discontinue the dietary restriction from their childhood develop minor neurological impairments. However, PKU patients with late-onset severe neurological symptoms are very rare. To our knowledge, this is the first report regarding SPECT findings of PKU patients with late-onset severe neurological deterioration. Copyright © 2015 Elsevier Ltd. All rights reserved.

What Causes Prader-Willi Syndrome?

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... a fundamental role in regulating hunger and fullness. Maternal uniparental disomy (pronounced yoo-nuh-puh-REN-tl ... 2018). Prader-Willi syndrome and early-onset morbid obesity NIH rare disease consortium: A review of natural ...

Neonatal abstinence syndrome: Diagnostic dilemmas in the maternity ward

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Lazić-Mitrović Tanja

2015-01-01

Full Text Available Introduction. Neonatal abstinence syndrome (NAS refers to a newborn neurological, gastrointestinal and/or respiratory disorder if a newborn was exposed to psychoactive substances in the intrauterine period. NAS is difficult to diagnose due to unreliability of the data on addictive substances use during pregnancy, limited possibilities of the prenatal exposure diagnosis and postnatal substance detection, which all lead to diagnostic dilemmas. Objective. The aim of this study was to indicate the problems in patients with early NAS diagnosis in the maternity ward and the importance of clinical presentation used as a guide toward the diagnosis. Methods. This retrospective study included five term eutrophic newborns with high Apgar score, good adaptation in the first day and with clinical presentation of NAS during the second day of life. The clinical presentation was dominated by irritability, increased wakefulness, increased muscle tone, shrilly crying, tremors, problems with accepting food, tachypnea, subfebrility and hyperhidrosis. Finnegan scale was introduced in order to diagnose NAS and apply the therapy. Single-medication therapy of phenobarbitone was applied in four cases and a combination of phenobarbitone and morphine in one case. For toxicological analysis newborns’ urine samples were used. Results. Conditions such as perinatal asphyxia, infection, hunger, polycythemia, hypoglycemia or hypocalcemia were excluded. Finnegan score implied that pharmacological treatment had to be administered. The discrepancy between the NAS anamnesis and toxicological analysis existed. Response to the treatment was positive in all cases. Conclusion. NAS is a multisystemic disorder and should be suspected when it is noticed that children exhibit characteristic signs. However, other pathological conditions have to be excluded. Quantification according to the adopted scales for NAS leads toward appropriate treatment and recovery of the newborns.

Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China.

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Liu, Ning; Huang, Qiuying; Li, Qingge; Zhao, Dehua; Li, Xiaole; Cui, Lixia; Bai, Ying; Feng, Yin; Kong, Xiangdong

2017-10-05

Phenylketonuria (PKU), which primarily results from a deficiency of phenylalanine hydroxylase (PAH), is one of the most common inherited inborn errors of metabolism that impairs postnatal cognitive development. The incidence of various PAH variations differs by race and ethnicity. The aim of the present study was to characterize the PAH gene variants of a Han population from Northern China. In total, 655 PKU patients and their families were recruited for this study; each proband was diagnosed both clinically and biochemically with phenylketonuria. Subjects were sequentially screened for single-base variants and exon deletions or duplications within PAH via direct Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). A spectrum of 174 distinct PAH variants was identified: 152 previously documented variants and 22 novel variants. While single-base variants were distributed throughout the 13 exons, they were particularly concentrated in exons 7 (33.3%), 11 (14.2%), 6 (13.2%), 12 (11.0%), 3 (10.4%), and 5 (4.4%). The predominant variant was p.Arg243Gln (17.7%), followed by Ex6-96A > G (8.3%), p.Val399 = (6.4%), p.Arg53His (4.7%), p.Tyr356* (4.7%), p.Arg241Cys (4.6%), p.Arg413Pro (4.6%), p.Arg111* (4.4%), and c.442-1G > A (3.4%). Notably, two patients were also identified as carrying de novo variants. The composition of PAH gene variants in this Han population from Northern China was distinct from those of other ethnic groups. As such, the construction of a PAH gene variant database for Northern China is necessary to lay a foundation for genetic-based diagnoses, prenatal diagnoses, and population screening.

New protein structures provide an updated understanding of phenylketonuria.

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Jaffe, Eileen K

2017-08-01

Phenylketonuria (PKU) and less severe hyperphenylalaninemia (HPA) constitute the most common inborn error of amino acid metabolism, and is most often caused by defects in phenylalanine hydroxylase (PAH) function resulting in accumulation of Phe to neurotoxic levels. Despite the success of dietary intervention in preventing permanent neurological damage, individuals living with PKU clamor for additional non-dietary therapies. The bulk of disease-associated mutations are PAH missense variants, which occur throughout the entire 452 amino acid human PAH protein. While some disease-associated mutations affect protein structure (e.g. truncations) and others encode catalytically dead variants, most have been viewed as defective in protein folding/stability. Here we refine this view to address how PKU-associated missense variants can perturb the equilibrium among alternate native PAH structures (resting-state PAH and activated PAH), thus shifting the tipping point of this equilibrium to a neurotoxic Phe concentration. This refined view of PKU introduces opportunities for the design or discovery of therapeutic pharmacological chaperones that can help restore the tipping point to healthy Phe levels and how such a therapeutic might work with or without the inhibitory pharmacological chaperone BH 4 . Dysregulation of an equilibrium of architecturally distinct native PAH structures departs from the concept of "misfolding", provides an updated understanding of PKU, and presents an enhanced foundation for understanding genotype/phenotype relationships. Copyright © 2017 Elsevier Inc. All rights reserved.

Advances in the nutritional and pharmacological management of phenylketonuria

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Ney, Denise M.; Blank, Robert D.; Hansen, Karen E.

2014-01-01

Structural Abstract Purpose of review The purpose is to discuss advances in the nutritional and pharmacological management of phenylketonuria (PKU). Recent findings Glycomacropeptide (GMP), a whey protein produced during cheese production, is a low-phe intact protein that represents a new dietary alternative to synthetic amino acids (AAs) for people with PKU. Skeletal fragility is a long-term complication of PKU that based on murine research, appears to result from both genetic and nutritional factors. Skeletal fragility in murine PKU is attenuated with the GMP diet, compared with an AA diet, allowing greater radial bone growth. Pharmacologic therapy with tetrahydrobiopterin (BH4), acting as a molecular chaperone for phenylalanine hydroxylase, increases tolerance to dietary phe in some individuals. Large neutral AAs (LNAA) inhibit phe transport across the intestinal mucosa and blood brain barrier; LNAA are most effective for individuals unable to comply with the low-phe diet. Summary Although a low-phe synthetic AA diet remains the mainstay of PKU management, new nutritional and pharmacological treatment options offer alternative approaches to maintain lifelong low phe concentrations. GMP medical foods provide an alternative to AA formula that may improve bone health, and BH4 permits some individuals with PKU to increase tolerance to dietary phe. Further research is needed to characterize the long-term efficacy of these new approaches for PKU management. PMID:24136088

The Prevalence of Phenylketonuria in Arab Countries, Turkey, and Iran: A Systematic Review

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Ashraf El-Metwally

2018-01-01

Full Text Available Background/Objectives. This paper seeks to identify the prevalence of Phenylketonuria (PKU in Arab countries, Turkey, and Iran. The study reviewed the existence of comprehensive national newborn screening programs and reported consanguinity rates. Methods. A computer based literature search was conducted using relevant keywords to retrieve studies conducted on PKU. A total of 34 articles were included. Prevalence was categorized based on the type of screening method used for PKU diagnoses. Results. The prevalence of classical PKU diagnosed through a comprehensive national newborn screening program ranged from 0.005% to 0.0167%. The highest prevalence was reported in Turkey at 0.0167%, whereas the lowest prevalence was reported in the UAE, 0.005%. Conclusion. The findings of this review emphasize the need for the establishment of more efficient reporting systems in these countries that would help measure Disability-Adjusted Life Year (DALY in order to estimate the overall societal burden of PKU.

Imaging clues in the prenatal diagnosis of syndromes and aneuploidy

International Nuclear Information System (INIS)

Estroff, Judy A.

2012-01-01

Advances in fetal sonography and MRI have increased both the range and diagnostic accuracy of detectable fetal anomalies, with many anomalies detectable earlier in pregnancy. The presence of structural anomalies greatly raises the risk that the fetus has a syndrome or abnormal karyotype. In addition, new techniques in maternal serum screening have greatly increased the ability to identify pregnant patients at risk for anomalies and syndromes. This paper reviews maternal first- and second-trimester serum screening and imaging and covers many of the most common fetal karyotypic and structural anomalies. (orig.)

Imaging clues in the prenatal diagnosis of syndromes and aneuploidy

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Estroff, Judy A. [Harvard Medical School, Fetal-Neonatal Radiology, Boston, MA (United States); Children' s Hospital Boston, Advanced Fetal Care Center, Department of Radiology, Boston, MA (United States)

2012-01-15

Advances in fetal sonography and MRI have increased both the range and diagnostic accuracy of detectable fetal anomalies, with many anomalies detectable earlier in pregnancy. The presence of structural anomalies greatly raises the risk that the fetus has a syndrome or abnormal karyotype. In addition, new techniques in maternal serum screening have greatly increased the ability to identify pregnant patients at risk for anomalies and syndromes. This paper reviews maternal first- and second-trimester serum screening and imaging and covers many of the most common fetal karyotypic and structural anomalies. (orig.)

Brain MRI diffusion-weighted imaging in patients with classical phenylketonuria

International Nuclear Information System (INIS)

Manara, Renzo; Citton, Valentina; Carollo, Carla; Burlina, Alessandro P.; Ermani, Mario; Vespignani, Francesco; Burlina, Alberto B.

2009-01-01

The aim of this study was to grade magnetic resonance white matter abnormalities (WMAs) of classical phenylketonuria (cPKU) patients treated from birth and to compare sensitivity and specificity of T2-weighted and diffusion-weighted images (DWI). Twenty early-treated cPKU patients still on a low-phenylalanine diet (12 males; mean age 21.2 years) and 26 normal subjects (ten males; mean age 25.1 years) were enrolled. Typical T2- and diffusion-weighted WMAs were semiquantitatively graded according to Thompson score (TS). Besides, a regional magnetic resonance imaging (MRI) score (mTS) was developed according to extension and intensity of WMAs. Phenylalanine and tyrosine plasma concentrations before performing MRI and the amino acid mean levels collected the year before MRI (Tyr year and Phe year ) were measured. No patient with Phe year concentration below 460 μmol/L showed WMAs. In cPKU patients, TS and mTS were significantly higher on DWI than on T2 images (3.50 vs 2.65 and 23.65 vs 15.85, respectively, p year levels. Among the different MR sequences, DWI seems to be the most sensitive and reliable in detecting and grading the typical WMAs of cPKU patients. (orig.)

"I Feel Lucky" - Gratitude Among Young Adults with Phenylketonuria (PKU).

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Diesen, Plata Sofie

2016-10-01

If persons with phenylketonuria (PKU) do not start a protein restricted diet in early infancy, they will suffer severe brain damage. Previous qualitative research on adults and adolescents with PKU has identified stigmatization, uncertain risk perceptions, considerable time spent on preparing food, and incongruence between the PKU diet and certain lifestyle demands. The aim of this study was to explore young and early treated Norwegian adults' experiences, by conducting in-depth interviews in 2011 with 11 adults with PKU, aged 20-30. Being the first qualitative study on people with PKU in Norway, the process was inspired by grounded theory. All participants reflected on their own health and existence by expressing positive counterfactual thoughts. They considered themselves lucky to have had parents who had managed the diet, they were grateful for the time and place they were born, and for information and treatment availability, although the results also show some ambiguous attitudes towards the hospital which provided the treatment. The expression of gratitude in association with having PKU suggests a major positive coping strategy. It contributes to a more holistic understanding of the experiences and attitudes of young, Norwegian adults with PKU, as it provides a counterweight to the negative experiences.

Chilean model for long-term follow-up of phenylketonuria (PKU

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Verónica Cornejo

2014-07-01

Full Text Available Chilean newborn screening program began in 1984 through of a covenant between the National Ministry of Health and the Chilean University through its Institute of Nutrition and Food Technology (INTA with the aim of implementing a pilot study for neonatal detection of phenylketonuria (PKU in Santiago’s central area. In 1989 a program for neonatal diagnosis of PKU and congenital hypothyroidism (HC was initiated by INTA along with Santiago´s occidental health ministry rural area, which covered 20% of newborn population. PKU and HC had an incidence of 1:14,640 and 1:2000 living newborns respectively. These findings allowed the establishment of a favorable cost/benefit ratio which validated the implementation of a program with National character. In 1992 the Chilean Ministry of Health ruled the initiation of PKU and HC newborn screening program and by 1998 the coverage across the country was achieved. INTA is the National Reference Center for confirmation and long term treatment for PKU and HC patients. A follow-up program consists of medical, nutritional, neurological and psychological outcome evaluations as well as periodic biochemical testing in order to guarantee normal patient growth and development. To date 184 children have been diagnosed with classic or moderate PKU, all of them follow a strict monitoring program.

A Case of Alloimmune Thrombocytopenia, Hemorrhagic Anemia-Induced Fetal Hydrops, Maternal Mirror Syndrome, and Human Chorionic Gonadotropin–Induced Thyrotoxicosis

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Venu Jain

2013-05-01

Full Text Available Fetal/neonatal alloimmune thrombocytopenia (FNAIT can be a cause of severe fetal thrombocytopenia, with the common presentation being intracranial hemorrhage in the fetus, usually in the third trimester. A very unusual case of fetal anemia progressed to hydrops. This was further complicated by maternal Mirror syndrome and human chorionic gonadotropin–induced thyrotoxicosis. Without knowledge of etiology, and possibly due to associated cardiac dysfunction, fetal transfusion resulted in fetal demise. Subsequent testing revealed FNAIT as the cause of severe hemorrhagic anemia. In cases with fetal anemia without presence of red blood cell antibodies, FNAIT must be ruled out as a cause prior to performing fetal transfusion. Fetal heart may adapt differently to acute hemorrhagic anemia compared with a more subacute hemolytic anemia.

Shape analysis of corpus callosum in phenylketonuria using a new 3D correspondence algorithm

Science.gov (United States)

He, Qing; Christ, Shawn E.; Karsch, Kevin; Peck, Dawn; Duan, Ye

2010-03-01

Statistical shape analysis of brain structures has gained increasing interest from neuroimaging community because it can precisely locate shape differences between healthy and pathological structures. The most difficult and crucial problem is establishing shape correspondence among individual 3D shapes. This paper proposes a new algorithm for 3D shape correspondence. A set of landmarks are sampled on a template shape, and initial correspondence is established between the template and the target shape based on the similarity of locations and normal directions. The landmarks on the target are then refined by iterative thin plate spline. The algorithm is simple and fast, and no spherical mapping is needed. We apply our method to the statistical shape analysis of the corpus callosum (CC) in phenylketonuria (PKU), and significant local shape differences between the patients and the controls are found in the most anterior and posterior aspects of the corpus callosum.

Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.

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Yong-Hui Jiang

2010-08-01

Full Text Available Angelman syndrome (AS is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11-q13 (70%, paternal uniparental disomy (UPD of chromosome 15 (5%, imprinting mutations (rare, and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%. Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11-q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m-/p+ were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m-/p+, but not paternal (m+/p-, deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal

Maternal placental syndromes: pathological mechanisms and long-term consequences

NARCIS (Netherlands)

Veerbeek, J.H.W.

2015-01-01

Preeclampsia, intra uterine growth restriction (IUGR) and placental abruption are major contributors to maternal and perinatal morbidity and mortality. In these disorders the placenta is a key aetiological factor and therefore preeclampsia, IUGR and placental abruption are also referred to as

Age–related psychophysiological vulnerability to phenylalanine in phenylketonuria

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Vincenzo eLeuzzi

2014-06-01

Full Text Available Background. Phenylketonuria (PKU is caused by the inherited defect of the phenylalanine hydroxylase enzyme, which converts phenylalanine (Phe into tyrosine (Tyr. Neonatal screening programs and early treatment have radically changed the natural history of PKU. Nevertheless, an increased risk of neurocognitive and psychiatric problems in adulthood remains a challenging aspect of the disease. In order to assess the vulnerability of complex skills to Phe, we explored: a the effect of a rapid increase in blood Phe levels on event-related potentials (ERP in PKU subjects during their second decade of life; b the association (if existing between psychophysiological and neurocognitive features.Methods. Seventeen early-treated PKU subjects, aged 10 to 20, underwent ERP (Mismatch Negativity, auditory P300, Contingent Negative Variation (CNV, and Intensity Dependence of Auditory Evoked Potentials recording before and 2 hours after an oral loading of Phe. Neurocognitive functioning, historical and concurrent biochemical values of blood Phe, Tyr, and Phe/Tyr ratio, were all included in the statistical analysis.Results. ERP components were normally detected in all the subjects. In subjects younger than 13 CNV amplitude, W2-CNV area, P3b latency, and Reaction Times in motor responses were negatively influenced by Phe loading. Independently from the psychophysiological vulnerability, some neurocognitive skills were more impaired in younger patients. No correlation was found between biochemical alterations and neurocognitive and psychophysiological findings. Conclusion. The vulnerability of the emerging neurocognitive functions to Phe suggests a strict metabolic control in adolescents affected by PKU and a neurodevelopmental approach in the study of neurocognitive outcome in PKU.

to generation

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Michał Otręba

2014-09-01

Full Text Available Inherited diseases of pigmentation were among the first traits studied in humans because of their easy recognition. This article presents selected hypopigmentary disorders, which can be divided into hypomelanocytoses and hypomelanoses. Hereditary hypomelanoses are caused by abnormal melanin biosynthesis as well as by abnormal transfer of mature melanosomes to melanocyte dendrites and to neighboring cells. These disorders are represented by oculocutaneous albinism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Griscelli syndrome, Menkes syndrome and phenylketonuria, and are caused by different mutations of the following genes: TYR, P, TRP1, MATP, HPS, CHS, MYO5A, RAB27A, MLPH, ATP7A and PAH. Oculocutaneous albinism is caused by a deficiency of melanin pigment in the skin, hair, and eye and results from mutations in the TYR, P, TRP1 and MATP genes involved in the biosynthesis of melanin pigment. Mutations in the HPS, CHS, MYO5A, RAB27A and MLPH genes, which regulate the biogenesis, maturation and transfer of me-lanosomes to neighboring cells, are responsible for such disorders as Hermansky-Pudlak, Chediak-Higashi and Griscelli syndromes. In turn, mutations of the ATP7A and PAH genes, regulating intracellular copper concentration and activity of phenylalanine hydroxylase, lead to Menkes syndrome and phenylketonuria.

ALPHA-FETOPROTEIN IN FETAL SERUM, AMNIOTIC-FLUID, AND MATERNAL SERUM

NARCIS (Netherlands)

VANLITH, JMM; BEEKHUIS, [No Value; VANLOON, AJ; MANTINGH, A; DEWOLF, BTHM; BREED, ASPM

In order to gain more insight into the association between alpha-fetoprotein (AFP) and fetal chromosomal disorders, especially Down's syndrome, we measured AFP in fetal serum, amniotic fluid, and maternal serum at cordocentesis. We compared the concentration and gradient of AFP in these three

Arterial stiffness assessment in patients with phenylketonuria

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Hermida-Ameijeiras, Alvaro; Crujeiras, Vanesa; Roca, Iria; Calvo, Carlos; Leis, Rosaura; Couce, María-Luz

2017-01-01

Abstract In patients with phenylketonuria (PKU) compliant to diet greater tendency to overweight and higher inflammatory biomarkers levels than controls were reported. Although this could lead to atherogenesis, the elastic properties of large arteries in PKU patients have never been assessed. The aim of this study was to assess arterial stiffness measured by applanation tonometry in PKU patients compared to healthy controls. We carried out a cross-sectional study in 41 PKU patients (range age: 6–50 years old) and 41 age- and gender-matched healthy controls. Evaluated data included pharmacological treatment with sapropterin, clinical, and biochemical parameters. Aortic stiffness was assessed noninvasively by applanation tonometry measuring central blood pressure, aortic augmentation index (Aix@HR75), augmentation pressure (AP), and pulse wave velocity (PWV). We found higher PWV in classic PKU patients (6.60 m/second vs 5.26 m/second; P: .044). Percentage of PKU patients with PWV above 90 percentile was higher than controls (14.63% vs 2.32%; P: .048). A positive relationship was observed between the annual Phe median and PWV (r: 0.496; P: .012). PKU subjects with lower Phe tolerance showed more body weight (67.6 kg vs 56.8 kg; P: .012) and more PWV than those with higher Phe tolerance (6.55 m/second vs 5.42 m/second; P: .044). Our data show increased aortic stiffness in PKU patients, measured by applanation tonometry, when compared to healthy controls. Higher Phe levels are associated with a bigger PWV increase, which is not present in those subjects compliant to diet or under sapropterin treatment. These results could have marked effects in both research and clinical daily practice for a proper evaluation of cardiovascular risk in PKU subjects. PMID:29390507

Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (IV)

OpenAIRE

Chen, Chih-Ping

2008-01-01

Fetuses with neural tube defects (NTDs) may be associated with maternal and fetal risk factors. This article provides a comprehensive review of maternal and fetal risk factors associated with NTDs, such as infertility, periconceptional clomiphene use and assisted reproductive technology, periconceptional folic acid deficiency and effects offolic acid supplementation and fortification on NTD rates, periconceptional vitamin B1 2 deficiency, single nucleotide polymorphisms and polymorphisms in g...

Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria.

Science.gov (United States)

Demirdas, Serwet; van Spronsen, Francjan J; Hollak, Carla E M; van der Lee, J Hanneke; Bisschop, Peter H; Vaz, Fred M; Ter Horst, Nienke M; Rubio-Gozalbo, M Estela; Bosch, Annet M

2017-01-01

In phenylketonuria (PKU), a natural protein-restricted dietary treatment prevents severe cognitive impairment. Nutrient deficiencies may occur due to strict diet. This study is aimed at evaluating the dietary intake and blood concentrations of micronutrients and essential fatty acids (FA), bone mineral density (BMD) and fracture history in patients on long-term dietary treatment. Sixty early diagnosed Dutch patients (aged 1-39 years) were included in a multi-center cross-sectional study. Their dietary intake, blood concentrations of micronutrients, FA, fracture history and BMD were assessed. Selenium dietary intake and serum concentrations were low in 14 and 46% of patients, respectively. The serum 25-OH vitamin D2 + D3 concentration was low in 14% of patients while 20% of patients had a low vitamin D intake. Zinc serum concentrations were below normal in 14% of patients, despite adequate intake. Folic acid serum concentrations and intake were elevated. Despite safe total protein and fat intake, arginine plasma concentrations and erythrocyte eicosapentaenoic acid were below reference values in 19 and 6% of patients, respectively. Low BMD (Z-score <-2) was slightly more prevalent in patients, but the lifetime fracture prevalence was comparable to the general population. Dutch patients with PKU on long-term dietary treatment have a near normal nutrient status. Supplementation of micronutrients of which deficiency may be deleterious (e.g., vitamin D and selenium) should be considered. BMD warrants further investigation. © 2017 S. Karger AG, Basel.

Maternal leptin and body composition in the first trimester of pregnancy.

LENUS (Irish Health Repository)

Fattah, Chro

2012-02-01

BACKGROUND: Leptin is produced mainly by adipocytes. Levels are increased in women with obesity and during pregnancy. Increased levels are also associated with pregnancy complications such as, pre-eclampsia and gestational diabetes mellitus. OBJECTIVE: We studied what component of body composition correlated best with maternal leptin in the first trimester of pregnancy and, whether maternal leptin correlated better with visceral fat rather than fat distributed elsewhere. SUBJECTS AND METHODS: Women were recruited in the first trimester. Maternal adiposity was measured using body mass index and advanced bioelectrical impedance analysis. Maternal leptin was measured using an enzyme-linked immunosorbent assay technique. RESULTS: Of the 100 subjects studied, the mean leptin concentration was 37.7 ng\\/ml (range: 2.1-132.8). Leptin levels did not correlate with gestational age in the first trimester, maternal age, parity or birth weight. Serum leptin correlated positively with maternal weight and body mass index, and with the different parameters of body composition. On multiple regression analysis, serum leptin correlated with visceral fat but not fat distributed elsewhere. CONCLUSIONS: Visceral fat is the main determinant of circulating maternal leptin in the first trimester of pregnancy. This raises the possibility that maternal leptin in early pregnancy may be a marker for the development of metabolic syndrome, including diabetes mellitus.

Epigenomics, gestational programming and risk of metabolic syndrome.

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Desai, M; Jellyman, J K; Ross, M G

2015-04-01

Epigenetic mechanisms are emerging as mediators linking early environmental exposures during pregnancy with programmed changes in gene expression that alter offspring growth and development. There is irrefutable evidence from human and animal studies that nutrient and environmental agent exposures (for example, endocrine disruptors) during pregnancy may affect fetal/newborn development resulting in offspring obesity and obesity-associated metabolic abnormalities (metabolic syndrome). This concept of 'gestational programming' is associated with alterations to the epigenome (nongenomic) rather than changes in the DNA sequence (genomic). Epigenetic alterations induced by suboptimal maternal nutrition/endocrine factors include DNA methylation, histone modifications, chromatin remodeling and/or regulatory feedback by microRNAs, all of which have the ability to modulate gene expression and promote the metabolic syndrome phenotype. Recent studies have shown tissue-specific transcriptome patterns and phenotypes not only in the exposed individual, but also in subsequent progeny. Notably, the transmission of gestational programming effects to subsequent generations occurs in the absence of continued adverse environmental exposures, thus propagating the cycle of obesity and metabolic syndrome. This phenomenon may be attributed to an extrinsic process resulting from the maternal phenotype and the associated nutrient alterations occurring within each pregnancy. In addition, epigenetic inheritance may occur through somatic cells or through the germ line involving both maternal and paternal lineages. Since epigenetic gene modifications may be reversible, understanding how epigenetic mechanisms contribute to transgenerational transmission of obesity and metabolic dysfunction is crucial for the development of novel early detection and prevention strategies for programmed metabolic syndrome. In this review we discuss the evidence in human and animal studies for the role of

Application of Neural Networks for classification of Patau, Edwards, Down, Turner and Klinefelter Syndrome based on first trimester maternal serum screening data, ultrasonographic findings and patient demographics.

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Catic, Aida; Gurbeta, Lejla; Kurtovic-Kozaric, Amina; Mehmedbasic, Senad; Badnjevic, Almir

2018-02-13

The usage of Artificial Neural Networks (ANNs) for genome-enabled classifications and establishing genome-phenotype correlations have been investigated more extensively over the past few years. The reason for this is that ANNs are good approximates of complex functions, so classification can be performed without the need for explicitly defined input-output model. This engineering tool can be applied for optimization of existing methods for disease/syndrome classification. Cytogenetic and molecular analyses are the most frequent tests used in prenatal diagnostic for the early detection of Turner, Klinefelter, Patau, Edwards and Down syndrome. These procedures can be lengthy, repetitive; and often employ invasive techniques so a robust automated method for classifying and reporting prenatal diagnostics would greatly help the clinicians with their routine work. The database consisted of data collected from 2500 pregnant woman that came to the Institute of Gynecology, Infertility and Perinatology "Mehmedbasic" for routine antenatal care between January 2000 and December 2016. During first trimester all women were subject to screening test where values of maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (β-hCG) were measured. Also, fetal nuchal translucency thickness and the presence or absence of the nasal bone was observed using ultrasound. The architectures of linear feedforward and feedback neural networks were investigated for various training data distributions and number of neurons in hidden layer. Feedback neural network architecture out performed feedforward neural network architecture in predictive ability for all five aneuploidy prenatal syndrome classes. Feedforward neural network with 15 neurons in hidden layer achieved classification sensitivity of 92.00%. Classification sensitivity of feedback (Elman's) neural network was 99.00%. Average accuracy of feedforward neural network was 89.6% and for

Prenatal Screening Using Maternal Markers

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Howard Cuckle

2014-05-01

Full Text Available Maternal markers are widely used to screen for fetal neural tube defects (NTDs, chromosomal abnormalities and cardiac defects. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia. The methods initially developed for NTDs using a single marker have since been built upon to develop high performance multi-maker tests for chromosomal abnormalities. Although cell-free DNA testing is still too expensive to be considered for routine application in public health settings, it can be cost-effective when used in combination with existing multi-maker marker tests. The established screening methods can be readily applied in the first trimester to identify pregnancies at high risk of pre-eclampsia and offer prevention though aspirin treatment. Prenatal screening for fragile X syndrome might be adopted more widely if the test was to be framed as a form of maternal marker screening.

Single-dose, subcutaneous recombinant phenylalanine ammonia lyase conjugated with polyethylene glycol in adult patients with phenylketonuria: an open-label, multicentre, phase 1 dose-escalation trial.

Science.gov (United States)

Longo, Nicola; Harding, Cary O; Burton, Barbara K; Grange, Dorothy K; Vockley, Jerry; Wasserstein, Melissa; Rice, Gregory M; Dorenbaum, Alejandro; Neuenburg, Jutta K; Musson, Donald G; Gu, Zhonghua; Sile, Saba

2014-07-05

Phenylketonuria is an inherited disease caused by impaired activity of phenylalanine hydroxylase, the enzyme that converts phenylalanine to tyrosine, leading to accumulation of phenylalanine and subsequent neurocognitive dysfunction. Phenylalanine ammonia lyase is a prokaryotic enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. We aimed to assess the safety, tolerability, pharmacokinetic characteristics, and efficacy of recombinant Anabaena variabilis phenylalanine ammonia lyase (produced in Escherichia coli) conjugated with polyethylene glycol (rAvPAL-PEG) in reducing phenylalanine concentrations in adult patients with phenylketonuria. In this open-label, phase 1, multicentre trial, single subcutaneous injections of rAvPAL-PEG were given in escalating doses (0·001, 0·003, 0·010, 0·030, and 0·100 mg/kg) to adults with phenylketonuria. Participants aged 18 years or older with blood phenylalanine concentrations of 600 μmol/L or higher were recruited from among patients attending metabolic disease clinics in the USA. The primary endpoints were safety and tolerability of rAvPAL-PEG. Secondary endpoints were the pharmacokinetic characteristics of the drug and its effect on concentrations of phenylalanine. Participants and investigators were not masked to assigned dose group. This study is registered with ClinicalTrials.gov, number NCT00925054. 25 participants were recruited from seven centres between May 6, 2008, and April 15, 2009, with five participants assigned to each escalating dose group. All participants were included in the safety population. The most frequently reported adverse events were injection-site reactions and dizziness, which were self-limited and without sequelae. Two participants had serious adverse reactions to intramuscular medroxyprogesterone acetate, a drug that contains polyethylene glycol as an excipient. Three of five participants given the highest dose of rAvPAL-PEG (0·100 mg/kg) developed a generalised skin rash

Post-Traumatic Stress Disorder and severe maternal morbidity: is there an association?

Science.gov (United States)

Angelini, Carina R; Pacagnella, Rodolfo C; Parpinelli, Mary A; Silveira, Carla; Andreucci, Carla B; Ferreira, Elton C; Santos, Juliana P; Zanardi, Dulce M; Souza, Renato T; Cecatti, Jose G

2018-01-01

To evaluate the occurrence of Post-Traumatic Stress Disorder among women experiencing a severe maternal morbidity event and associated factors in comparison with those without maternal morbidity. In a retrospective cohort study, 803 women with or without severe maternal morbidity were evaluated at 6 months to 5 years postpartum for the presence of Post-Traumatic Stress Disorder. Interviews were conducted by telephone and electronic data was stored. Data analysis was carried out by using χ2, Fisher's Exact test, and logistic regression analysis. There was no significant change in the prevalence of Post-Traumatic Stress Disorder related to a previous severe maternal morbidity experience. There were also no differences in diagnostic criteria for severe maternal morbidity (hypertensive syndromes, hemorrhage, surgical intervention or intensive care unit admission required, among other management criteria). Low parity (2.5-fold risk) and increasing age were factors associated with Post-Traumatic Stress Disorder. A severe maternal morbidity episode is not associated with Post-Traumatic Stress Disorder symptoms within five years of the severe maternal morbidity event and birth. However, a more advanced maternal age and primiparity increased the risk of Post-Traumatic Stress Disorder. This does not imply that women who had experienced a severe maternal morbidity event did not suffer or need differentiated care.

Depression and anxiety among parents of phenylketonuria children

Science.gov (United States)

Gunduz, Mehmet; Arslan, Nur; Unal, Ozlem; Cakar, Sevim; Kuyum, Pınar; Bulbul, Selda F.

2015-01-01

Objective: To investigate the existence of depression and/or anxiety with underlying risk factors among parents of children with classical phenylketonuria (PKU). Methods: This cross-sectional study was conducted in the Division of Pediatric Metabolism, Ankara Children’s Hospital, Dokuz Eylul University, Kırıkkale University, and Erzurum Local Research Hospital, Turkey, between January and July 2014. Parents of 61 patients and 36 healthy controls completed the self-report questionnaires. We used Beck Depression Inventory (BDI) to assess the parental depression and State-Trait Anxiety Inventory S-T (STAI S-T) to assess parental anxiety. Results: Depression and anxiety scores were significantly higher in the case group (BDI 12.3±9.1; STAI-S: 38.2±9.6; STAI-T: 43.2±6.9) than controls (BDI: 5.4±4.1 p=0.000; STAI-S: 31.8±7.6 p=0.001; STAI-T: 37.0±7.2 p=0.000). Mothers of the patients had higher scores than the other parental groups (BDI: p=0.000, STAI-S: p=0.001 and STAI-T: p=0.000). Logistic regression analysis showed that low educational level of the parent was the only independent factor for depression (OR 9.96, 95% CI: 1.89-52.35, p=0.007) and state anxiety (OR: 6.99, 95% CI: 1.22-40.48, p=0.030) in the case group. Conclusion: A subset of parents with PKU patients have an anxiety or depressive disorder. Supportive services dealing with the parents of chronically ill children such as PKU are needed in order to reduce the level of anxiety. PMID:26492114

Growth and Final Height Among Children With Phenylketonuria.

Science.gov (United States)

Thiele, Alena G; Gausche, Ruth; Lindenberg, Cornelia; Beger, Christoph; Arelin, Maria; Rohde, Carmen; Mütze, Ulrike; Weigel, Johannes F; Mohnike, Klaus; Baerwald, Christoph; Scholz, Markus; Kiess, Wieland; Pfäffle, Roland; Beblo, Skadi

2017-11-01

Growth is an important criterion to evaluate health in childhood and adolescence, especially in patients depending on special dietary treatment. Phenylketonuria (PKU) is the most common inherited disease of amino acid metabolism. Patients with PKU depend on a special phenylalanine-restricted diet, low in natural protein. The study aimed to evaluate growth, growth rate, and target height in 224 patients with PKU. Retrospective, longitudinal analysis of standardized, yearly measurements of height, weight, and calculated growth rate (SD score [SDS]) of patients with PKU aged 0 to 18 years were conducted by using the national computerized CrescNet database. Inclusion was restricted to patients carried to term with a confirmed diagnosis of PKU or mild hyperphenylalaninemia determined by newborn screening and early treatment initiation. From birth to adulthood, patients with PKU were significantly shorter than healthy German children (height SDS at 18 years: -0.882 ± 0.108, P < .001). They missed their target height by 3 cm by adulthood (women: P = .02) and 5 cm (men: P = .01). In patients receiving casein hydrolysate during childhood, this was more pronounced compared with patients receiving amino acid mixtures ( P < .001). Growth rate was significantly reduced during their first 2 years of life and in puberty (growth rate SDS: -1.1 to -0.5 m/year, P < .001 and -0.5; P < .02). Early diagnosed, treated, and continuously monitored patients with PKU showed reduced height from birth onward. During the last 2 decades, this phenomenon attenuated, probably because of advances in PKU therapy related to protein supplements and special low-protein foods. Copyright © 2017 by the American Academy of Pediatrics.

Mother-Child Interaction as a Window to a Unique Social Phenotype in 22q11.2 Deletion Syndrome and in Williams Syndrome

Science.gov (United States)

Weisman, Omri; Feldman, Ruth; Burg-Malki, Merav; Keren, Miri; Geva, Ronny; Diesendruck, Gil; Gothelf, Doron

2015-01-01

Mother-child interactions in 22q11.2 Deletion syndrome (22q11.2DS) and Williams syndrome (WS) were coded for maternal sensitivity/intrusiveness, child's expression of affect, levels of engagement, and dyadic reciprocity. WS children were found to express more positive emotions towards their mothers compared to 22q11.2DS children and those with…

Founder effect of a prevalent phenylketonuria mutation in the Oriental population

Energy Technology Data Exchange (ETDEWEB)

Wang, Tao (Baylor College of Medicine, Houston, TX (United States) Chinese Academy of Medical Sciences, Beijing (China)); Okano, Yoshiyuki; Eisensmith, R.C.; Harvey, M.L.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (United States)); Lo, W.H.Y.; Yuan, Lifang (Chinese Academy of Medical Sciences, Beijing (China)); Huang, Shuzhen; Zeng, Yitao (Shanghai Children' s Hospital (China)); Furuyama, Junichi (Hyogo College of Medicine, Nishinomiya (Japan)); Oura, Toshiaki (Osaka Municipal Rehabilitation Center for the Disabled, Osaka (Japan)); Sommer, S.S. (Mayo Clinic/Foundation, Rochester, MN (United States))

1991-03-15

A missense mutation has been identified in the human phenylalanine hydroxylase Chinese patient with classic phenylketonuria (PKU). A G-to-C transition at the second base of codon 413 in exon 12 of the gene results in the substitution of Pro{sup 413} for Arg{sup 413} in the mutant protein. This mutation (R413P) results in negligible enzymatic activity when expressed in heterologous mammalian cells and is compatible with a classic PKU phenotype in the patient. Population genetic studies reveal that this mutation is tightly linked to restriction fragment length polymorphism haplotype 4, which is the predominant haplotype of the PAH locus in the Oriental population. It accounts for 13.8% of northern Chinese and 27% of Japanese PKU alleles, but it is rare in southern Chinese (2.2%) and is absent in the Caucasian population. The data demonstrate unambiguously that the mutation occurred after racial divergence of Orientals and Caucasians and suggest that the allele has spread throughout the Orient by a founder effect. Previous protein polymorphism studies in eastern Asia have led to the hypothesis that northern Mongoloids represented a founding population in Asia. The results are compatible with this hypothesis in that the PKU mutation might have occurred in northern Mongoloids and subsequently spread to the Chinese and Japanese populations.

Founder effect of a prevalent phenylketonuria mutation in the Oriental population

International Nuclear Information System (INIS)

Wang, Tao; Okano, Yoshiyuki; Eisensmith, R.C.; Harvey, M.L.; Woo, S.L.C.; Lo, W.H.Y.; Yuan, Lifang; Huang, Shuzhen; Zeng, Yitao; Furuyama, Junichi; Oura, Toshiaki; Sommer, S.S.

1991-01-01

A missense mutation has been identified in the human phenylalanine hydroxylase Chinese patient with classic phenylketonuria (PKU). A G-to-C transition at the second base of codon 413 in exon 12 of the gene results in the substitution of Pro 413 for Arg 413 in the mutant protein. This mutation (R413P) results in negligible enzymatic activity when expressed in heterologous mammalian cells and is compatible with a classic PKU phenotype in the patient. Population genetic studies reveal that this mutation is tightly linked to restriction fragment length polymorphism haplotype 4, which is the predominant haplotype of the PAH locus in the Oriental population. It accounts for 13.8% of northern Chinese and 27% of Japanese PKU alleles, but it is rare in southern Chinese (2.2%) and is absent in the Caucasian population. The data demonstrate unambiguously that the mutation occurred after racial divergence of Orientals and Caucasians and suggest that the allele has spread throughout the Orient by a founder effect. Previous protein polymorphism studies in eastern Asia have led to the hypothesis that northern Mongoloids represented a founding population in Asia. The results are compatible with this hypothesis in that the PKU mutation might have occurred in northern Mongoloids and subsequently spread to the Chinese and Japanese populations

Morphometric analysis of gray matter integrity in individuals with early-treated phenylketonuria.

Science.gov (United States)

Christ, Shawn E; Price, Mason H; Bodner, Kimberly E; Saville, Christopher; Moffitt, Amanda J; Peck, Dawn

2016-05-01

The most widely-reported neurologic finding in individuals with early-treated phenylketonuria (PKU) is abnormality in the white matter of the brain. In contrast, much less is known regarding the impact of PKU on cortical gray matter (GM) structures. Presently, we applied advanced morphometric methods to the analysis of high-resolution structural MRI images from a sample of 19 individuals with early-treated PKU and an age- and gender-matched comparison group of 22 healthy individuals without PKU. Data analysis revealed decreased GM volume in parietal cortex for the PKU group compared with the non-PKU group. A similar trend was observed for occipital GM volume. There was no evidence of group-related differences in frontal or temporal GM volume. Within the PKU group, we also found a significant relationship between blood phenylalanine levels and GM volume for select posterior cortical sub-regions. Taken together with previous research on white matter and gray matter abnormalities in PKU, the present findings point to the posterior cortices as the primary site of neurostructural changes related to early-treated PKU. Copyright © 2016 Elsevier Inc. All rights reserved.

Behavioural effects of phenylalanine-free amino acid tablet supplementation in intellectually disabled adults with untreated phenylketonuria

DEFF Research Database (Denmark)

Kalkanoğlu, H Serap; Ahring, Kirsten K; Sertkaya, Durdu

2005-01-01

AIM: To evaluate the effects of phenylalanine (Phe)-free essential amino acid (AA) tablets enriched in tyrosine and tryptophan on the performance of intellectually disabled adult patients with untreated phenylketonuria (PKU). METHODS: Phe-free AA tablets and placebo tablets were administered to 19....... The statistical significance of the results was tested by means of the Fisher's exact and Wilcoxon tests. RESULTS: The most significant changes were an improved concentration and the development of a meaningful smile, which were observed in 44% and 43% of the patients on AA tablet treatment, respectively......, but not patients on placebo. Other important but less significant changes included increased awareness of external stimuli (63%) and less self-injury (43%), and 40% were smiling and laughing occasionally. The mean overall rating increased from an initial value of 6.3 to 10.1 in patients when on AA tablet treatment...

Angelman syndrome in an inbred family

NARCIS (Netherlands)

Beuten, J.; Hennekam, R. C.; van Roy, B.; Mangelschots, K.; Sutcliffe, J. S.; Halley, D. J.; Hennekam, F. A.; Beaudet, A. L.; Willems, P. J.

1996-01-01

Angelman syndrome (AS) is characterized by severe mental retardation, absent speech, puppet-like movements, inappropriate laughter, epilepsy, and abnormal electroencephalogram. The majority of AS patients (approximately 65%) have a maternal deficiency within chromosomal region 15q11-q13, caused by

Prenatal exposure to very severe maternal obesity is associated with adverse neuropsychiatric outcomes in children.

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Mina, T H; Lahti, M; Drake, A J; Räikkönen, K; Minnis, H; Denison, F C; Norman, J E; Reynolds, R M

2017-01-01

Prenatal maternal obesity has been linked to adverse childhood neuropsychiatric outcomes, including increased symptoms of attention deficit hyperactivity disorder (ADHD), internalizing and externalizing problems, affective disorders and neurodevelopmental problems but few studies have studied neuropsychiatric outcomes among offspring born to very severely obese women or assessed potential familial confounding by maternal psychological distress. We evaluated neuropsychiatric symptoms in 112 children aged 3-5 years whose mothers had participated in a longitudinal study of obesity in pregnancy (50 very severe obesity, BMI ⩾40 kg/m2, obese class III and 62 lean, BMI 18.5-25 kg/m2). The mothers completed the Conners' Hyperactivity Scale, Early Symptomatic Syndrome Eliciting Neurodevelopmental Clinical Examination Questionnaire (ESSENCE-Q), Child's Sleep Habits Questionnaire (CSHQ), Strengths and Difficulties Questionnaire (SDQ), and Child Behavior Checklist (CBCL) to assess child neuropsychiatric symptoms. Covariates included child's sex, age, birthweight, gestational age, socioeconomic deprivation levels, maternal age, parity, smoking status during pregnancy, gestational diabetes and maternal concurrent symptoms of anxiety and depression assessed using State Anxiety of Spielberger State-Trait Anxiety Index (STAI) and General Health Questionnaire (GHQ), respectively. Children exposed to prenatal maternal very severe obesity had significantly higher scores in the Conners' Hyperactivity Scale; ESSENCE-Q; total sleep problems in CSHQ; hyperactivity, conduct problems and total difficulties scales of the SDQ; higher externalizing and total problems, anxious/depressed, aggressive behaviour and other problem syndrome scores and higher DSM-oriented affective, anxiety and ADHD problems in CBCL. Prenatal maternal very severe obesity remained a significant predictor of child neuropsychiatric problems across multiple scales independent of demographic factors, prenatal factors and

Minimally invasive (13)C-breath test to examine phenylalanine metabolism in children with phenylketonuria.

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Turki, Abrar; Murthy, Gayathri; Ueda, Keiko; Cheng, Barbara; Giezen, Alette; Stockler-Ipsiroglu, Sylvia; Elango, Rajavel

2015-01-01

Phenylketonuria (PKU) is an autosomal recessive disorder caused by deficiency of hepatic phenylalanine hydroxylase (PAH) leading to increased levels of phenylalanine in the plasma. Phenylalanine levels and phenylalanine hydroxylase (PAH) activity monitoring are currently limited to conventional blood dot testing. 1-(13)C-phenylalanine, a stable isotope can be used to examine phenylalanine metabolism, as the conversion of phenylalanine to tyrosine occurs in vivo via PAH and subsequently releases the carboxyl labeled (13)C as (13)CO2 in breath. Our objective was to examine phenylalanine metabolism in children with PKU using a minimally-invasive 1-(13)C-phenylalanine breath test ((13)C-PBT). Nine children (7 M: 2 F, mean age 12.5 ± 2.87 y) with PKU participated in the study twice: once before and once after sapropterin supplementation. Children were provided 6 mg/kg oral dose of 1-(13)C-phenylalanine and breath samples were collected at 20 min intervals for a period of 2h. Rate of CO2 production was measured at 60 min post-oral dose using indirect calorimetry. The percentage of 1-(13)C-phenylalanine exhaled as (13)CO2 was measured over a 2h period. Prior to studying children with PKU, we tested the study protocol in healthy children (n = 6; 4M: 2F, mean age 10.2 ± 2.48 y) as proof of principle. Production of a peak enrichment (Cmax) of (13)CO2 (% of dose) in all healthy children occurred at 20 min ranging from 17-29% of dose, with a subsequent return to ~5% by the end of 2h. Production of (13)CO2 from 1-(13)C-phenylalanine in all children with PKU prior to sapropterin treatment remained low. Following sapropterin supplementation for a week, production of (13)CO2 significantly increased in five children with a subsequent decline in blood phenylalanine levels, suggesting improved PAH activity. Sapropterin treatment was not effective in three children whose (13)CO2 production remained unchanged, and did not show a reduction in blood phenylalanine levels and improvement

Angelman syndrome in an inbred family

NARCIS (Netherlands)

J. Beuten (Joke); R.C.M. Hennekam (Raoul); B. van Roy (Bernadette); K. Mangelschots (Kathelijne); J.S. Sutcliffe (James); D.J.J. Halley (Dicky); R.C.M. Hennekam (Raoul); L. Beaudet (Lucille); P.J. Willems (Patrick)

1996-01-01

textabstractAngelman syndrome (AS) is characterized by severe mental retardation, absent speech, puppet-like movements, inappropriate laughter, epilepsy, and abnormal electroencephalogram. The majority of AS patients (≃ 65%) have a maternal deficiency within chromosomal region 15q11-q13, caused by

Gypsy Phenylketonuria: A point mutation of the phenylalanine hydroxylase gene in Gypsy families from Slovakia

Energy Technology Data Exchange (ETDEWEB)

Kalanin, J. [Institute for Clinical and Experical Medicine, Praha (Czechoslovakia); Takarada, Y. [Toyobo Research Center, Shiga (Japan); Kagawa, S.; Yamashita, K.; Ohtsuka, N.; Matsuoka, A. [Hyogo College of Medicine, Nishinomiya (Japan)

1994-01-15

A direct mutational analysis of the phenylalanine hydroxylase gene (PAH) in Gypsy families with phenylketonuria (PKU) has not yet been presented. However, they obviously represent a group at high risk for this inherited disease. The authors analyzed the PAH loci of 65 Gypsies originating from Eastern Slovakia by a combination of PCR amplification, direct sequencing and ASO hybridization. These studies uncovered 10 {open_quotes}classical PKU{close_quotes} patients to be homozygous for a R252W (CGG-TGG) transition, and 29 heterozygous carriers of this mutation. Fifteen control Caucasoid PKU patients from the Czech and Slovak Republics were selected. In this group they detected R252W mutation in two subjects (6.67% of all mutant alleles). Both were compound heterozygous for two different mutations. Previous haplotype studies of Welsh Gypsies with PKU were uninformative in the determination of heterozygosity. ASO hybridization served effectively for the consequent analyses in Gypsy PKU-related families and to identify the carriers among the unrelated subjects. 19 refs., 2 figs.

[Good's syndrome and congenital toxoplasmosis due to maternal reactivation during pregnancy].

Science.gov (United States)

Tahiri, J; Fouyssac, F; Morel, O; Maatouk, A

2017-05-01

Good syndrome is a rare condition in which thymoma is associated with hypogammaglobulinemia. It is characterized by an increased susceptibility to infections. We report a woman with Good's syndrome diagnosed after severe congenital toxoplasmosis in her daughter, even though she was immunized against this infection during pregnancy. This presentation is very unusual by its early diagnosis and to our knowledge is the first report of parasitic infection in this syndrome. Copyright © 2016. Published by Elsevier SAS.

Maternal Plasma and Amniotic Fluid Chemokines Screening in Fetal Down Syndrome

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Piotr Laudanski

2014-01-01

Full Text Available Objective. Chemokines exert different inflammatory responses which can potentially be related to certain fetal chromosomal abnormalities. The aim of the study was to determine the concentration of selected chemokines in plasma and amniotic fluid of women with fetal Down syndrome. Method. Out of 171 amniocentesis, we had 7 patients with confirmed fetal Down syndrome (15th–18th weeks of gestation. For the purpose of our control, we chose 14 women without confirmed chromosomal aberration. To assess the concentration of chemokines in the blood plasma and amniotic fluid, we used a protein macroarray, which allows the simultaneous determination of 40 chemokines per sample. Results. We showed significant decrease in the concentration of 4 chemokines, HCC-4, IL-28A, IL-31, and MCP-2, and increase in the concentration of CXCL7 (NAP-2 in plasma of women with fetal Down syndrome. Furthermore, we showed decrease in concentration of 3 chemokines, ITAC, MCP-3, MIF, and increase in concentration of 4 chemokines, IP-10, MPIF-1, CXCL7, and 6Ckine, in amniotic fluid of women with fetal Down syndrome. Conclusion. On the basis of our findings, our hypothesis is that the chemokines may play role in the pathogenesis of Down syndrome. Defining their potential as biochemical markers of Down syndrome requires further investigation on larger group of patients.

Epigenoty-pephenotype correlations in Silver-Russell syndrome

NARCIS (Netherlands)

Wakeling, E. L.; Abu Amero, S.; Alders, M.; Bliek, J.; Forsythe, E.; Kumar, S.; Lim, D. H.; MacDonald, F.; Mackay, D. J.; Maher, E. R.; Moore, G. E.; Poole, R. L.; Price, S. M.; Tangeraas, T.; Turner, C. L. S.; Van Haelst, M. M.; Willoughby, C.; Temple, I. K.; Cobben, J. M.

2010-01-01

Background Silver Russell syndrome (SRS) is characterised by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, triangular face and asymmetry. Maternal uniparental disomy (mUPD) of chromosome 7 and hypomethylation of the imprinting control region (ICR) 1 on chromosome

The impact of Folate Pathway Polymorphisms Combined to Nutritional Deficiency As a Maternal Predisposition Factor for Down Syndrome

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C. B. Santos-Rebouças

2008-01-01

Full Text Available Polymorphisms in genes encoding folate metabolizing enzymes have been linked to an increased risk of maternal chromosomal nondisjunction in several populations. With the purpose of evaluating this relationship, we compared the frequencies of 677C>T and 1298A>C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR and 66A>G in the methionine synthase reductase gene (MTRR between 103 young mothers of Down syndrome (DS individuals and 108 control mothers, whose offspring was karyotypically normal, correlating it with an estimative of folate and – related micronutrients levels intake. Maternal and paternal transmission frequencies of MTHFR 677T allele were also examined to access potential parent-of-origin effects. PCR-RFLP for genomic DNA was accomplished and allele/genotype frequencies differences were determined using the x2 test, whereas pattern of transmission of the MTHFR 677 allele was analyzed by transmission disequilibrium test. None of the polymorphisms seemed to be more frequent in case mothers than in controls, either individually or combined. The estimative of nutritional intake revealed that folate consumption median was inadequate in both groups, whereas methionine and zinc consumption medians were significantly greater in control mothers. It suggests that such interaction between genetic profile and environment could predispose this sub group of women to have a DS child. Additional studies focusing the interaction between nutritional intakes, biochemical data and folate pathway polymorphisms are needed to confirm the present results. The possibility of neutralize the biochemical negative effects of folate-related polymorphisms through oral supplementation could provide new targets for DS prevention.

The Role of KCNQ1 Mutations and Maternal Beta Blocker Use During Pregnancy in the Growth of Children With Long QT Syndrome

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Heta Huttunen

2018-04-01

Full Text Available ObjectiveTwo missense mutations in KCNQ1, an imprinted gene that encodes the alpha subunit of the voltage-gated potassium channel Kv7.1, cause autosomal dominant growth hormone deficiency and maternally inherited gingival fibromatosis. We evaluated endocrine features, birth size, and subsequent somatic growth of patients with long QT syndrome 1 (LQT1 due to loss-of-function mutations in KCNQ1.DesignMedical records of 104 patients with LQT1 in a single tertiary care center between 1995 and 2015 were retrospectively reviewed.MethodsClinical and endocrine data of the LQT1 patients were included in the analyses.ResultsAt birth, patients with a maternally inherited mutation (n = 52 were shorter than those with paternal inheritance of the mutation (n = 29 (birth length, −0.70 ± 1.1 SDS vs. −0.2 ± 1.0 SDS, P < 0.05. Further analyses showed, however, that only newborns (n = 19 of mothers who had received beta blockers during pregnancy were shorter and lighter at birth than those with paternal inheritance of the mutation (n = 29 (−0.89 ± 1.0 SDS vs. −0.20 ± 1.0 SDS, P < 0.05; and 3,173 ± 469 vs. 3,515 ± 466 g, P < 0.05. Maternal beta blocker treatment during the pregnancy was also associated with lower cord blood TSH levels (P = 0.011 and significant catch-up growth during the first year of life (Δ0.08 SDS/month, P = 0.004. Later, childhood growth of the patients was unremarkable.ConclusionLoss-of-function mutations in KCNQ1 are not associated with abnormalities in growth, whereas maternal beta blocker use during pregnancy seems to modify prenatal growth of LQT1 patients—a phenomenon followed by catch-up growth after birth.

Predictive equations underestimate resting energy expenditure in female adolescents with phenylketonuria

Science.gov (United States)

Quirk, Meghan E.; Schmotzer, Brian J.; Schmotzer, Brian J.; Singh, Rani H.

2010-01-01

Resting energy expenditure (REE) is often used to estimate total energy needs. The Schofield equation based on weight and height has been reported to underestimate REE in female children with phenylketonuria (PKU). The objective of this observational, cross-sectional study was to evaluate the agreement of measured REE with predicted REE for female adolescents with PKU. A total of 36 females (aged 11.5-18.7 years) with PKU attending Emory University’s Metabolic Camp (June 2002 – June 2008) underwent indirect calorimetry. Measured REE was compared to six predictive equations using paired Student’s t-tests, regression-based analysis, and assessment of clinical accuracy. The differences between measured and predicted REE were modeled against clinical parameters to determine to if a relationship existed. All six selected equations significantly under predicted measured REE (P< 0.005). The Schofield equation based on weight had the greatest level of agreement, with the lowest mean prediction bias (144 kcal) and highest concordance correlation coefficient (0.626). However, the Schofield equation based on weight lacked clinical accuracy, predicting measured REE within ±10% in only 14 of 36 participants. Clinical parameters were not associated with bias for any of the equations. Predictive equations underestimated measured REE in this group of female adolescents with PKU. Currently, there is no accurate and precise alternative for indirect calorimetry in this population. PMID:20497783

Mutation profiles of phenylketonuria in Quebec populations: Evidence of stratification and novel mutations

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Rozen, R.; Mascisch, A.; Scriver, C.R. (McGill Univ., Montreal (Canada)); Lambert, M. (Hopital Ste-Justine, Montreal (Canada)); Laframboise, R. (Centre Hospitalier Universite Laval, Quebec (Canada))

1994-08-01

Independent phenylketonuria (PKU) chromosomes (n=109) representing 80% of a proband cohort in Quebec province carry 18 different identified mutations in 20 different mutation/haplotype combinations. The study reported here, the third in a series on Quebec populations, was done in the Montreal region and predominantly on French Canadians. It has identified three novel mutations (A309D, D338Y, and 1054/1055delG [352fs]) and one unusual mutation/RFLP haplotype combination (E280K on Hp 2). The relative frequencies and distribution of PKU mutations were then compared in three regions and population subsets (eastern Quebec, French Canadian; western Quebec, French Canadian; and Montreal, non-French Canadian). The distributions of the prevalent and rare mutations are nonrandom and provide evidence for genetic stratification. The latter and the presence of eight unusual mutation/haplotype combinations in Quebec families with European ancestries (the aforementioned four and M1V, 165T, S349P, and R408W on Hp 1) corroborate demographic and anthropologic evidence, from elsewhere, for different origins of French Canadians in eastern and western Quebec. 29 refs., 1 fig., 1 tab.

Measurement of functional independence level and falls-risk in individuals with undiagnosed phenylketonuria.

LENUS (Irish Health Repository)

Mazur, Artur

2009-01-01

The aim of the study was to determine the level of functional independence in adult patients with previously undiagnosed or untreated phenylketonuria (PKU). The study was conducted among 400 intellectually impaired adult residents of Social Welfare Homes in South-Eastern Poland born prior to the introduction of neonatal PKU screening programs. PKU was screened by filter paper test using tandem mass spectrometry methods, and confirmed by gas chromatography-mass spectrometric analysis of PKU organic acids in urine. Degree of functional independence included the assessment of activities of daily living (Barthel Index) and measures of balance and gait (Tinetti scale). Eleven individuals with previously untreated PKU were identified whereby eight presented with moderate disability and three with mild disability. Six had a high risk of falls and five had a moderate risk of falls. This study indicates that there is considerable number of undiagnosed PKU patients within the Polish population who require assessment and management in order to reduce the impact of the neurological and neuropsychiatric problems associated with the condition. Appropriate therapy for those with undiagnosed PKU should, in particular, address the risk of falls.

Evaluation of Maternal Complications in Severe Preeclampsia in a University Hospital in Tirana

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Eriseida Ndoni

2016-02-01

Full Text Available BACKGROUND: Preeclampsia is a hypertensive multisystem disorder of pregnancy that complicates up to 10% of pregnancies worldwide and is one of the leading causes of maternal and perinatal morbidity and mortality. AIM: To evaluate maternal complications associated with severe preeclampsia. METHODS: This is a retrospective cross-sectional study conducted in the UHOG “Koço Gliozheni”, in Tirana. Primary outcomes evaluated: maternal death, eclampsia, stroke, HELLP syndrome, and pulmonary edema. Secondary outcomes: renal failure, admission in ICU, caesarean section, placental abruption, and postpartum hemorrhage. Fisher’s exact test and Chi-squared test were used as statistical methods. RESULTS: In women with severe preeclampsia we found higher rates of complications comparing to the group with preeclampsia. Eclampsia (1.5% vs. 7.1%, P < 0.001, HELLP syndrome (2.4% vs. 11.0%; P < 0.001, stroke (0.5% vs 1.9%, P = 0.105 pulmonary edema (0.25% vs. 1.3%, P = 0.0035, renal failure (0.9% vs. 2.6%, P = 0.107, admission in ICU (19.5% vs. 71.4%, P = 0.007, caesarean section rates (55.5% vs. 77%, P = 0.508, placental abruption (4.3% vs. 7.8%, P = 0.103 and severe postpartum hemorrhage (3.2% vs. 3.9%, P = 0.628. CONCLUSION: Severe preeclampsia is associated with high rates of maternal severe morbidity and early diagnosis and timely intervention can prevent life treating complications.

Developmental programming in response to maternal over-nutrition

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Maria eAlfaradhi

2011-06-01

Full Text Available Metabolic disorders have seen an increased prevalence in recent years in developed as well as developing countries. While it is clear lifestyle choices and habits have contributed to this epidemic, mounting evidence suggests the nutritional milieu during critical stages of development in early life can ‘program’ individuals to develop the metabolic syndrome later in life. Extensive epidemiological data presents an association between maternal obesity and nutrition during pregnancy and offspring obesity, and a number of animal models have been established in order to uncover the underlying mechanisms contributing to the programming of physiological systems. It is hard to distinguish the causal factors due to the complex nature of the maternal-fetal relationship; however, in order to develop adequate prevention strategies it is vital to identify which maternal factor(s – be it the diet, diet-induced obesity or weight gain – and at which time during early development instigate the programmed phenotype. Curtailing the onset of obesity at this early stage in life presents a promising avenue through which to stem the growing epidemic of obesity.

Epigenotype-phenotype correlations in Silver-Russell syndrome

NARCIS (Netherlands)

Wakeling, E. L.; Amero, S. Abu; Alders, M.; Bliek, J.; Forsythe, E.; Kumar, S.; Lim, D. H.; Macdonald, F.; Mackay, D. J.; Maher, E. R.; Moore, G. E.; Poole, R. L.; Price, S. M.; Tangeraas, T.; Turner, C. L. S.; van Haelst, M. M.; Willoughby, C.; Temple, I. K.; Cobben, J. M.

2010-01-01

Silver-Russell syndrome (SRS) is characterised by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, triangular face and asymmetry. Maternal uniparental disomy (mUPD) of chromosome 7 and hypomethylation of the imprinting control region (ICR) 1 on chromosome 11p15 are

Parenting of children with Down syndrome compared to fragile X syndrome.

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Sterling, Audra; Warren, Steven F

2018-01-01

Children with Down syndrome (DS) and fragile X syndrome (FXS) struggle with language development. Parenting variables, such as responsiveness to children's communication attempts (Maternal Responsivity), and techniques used to support and teach appropriate behavior (Behavior Management) are known to have a significant impact on early child development. We examined these two aspects of parenting style via coded, videotaped parent-child interactions in two groups of participants matched on child age (2-5 years) and child expressive language level: mothers of children with DS and mothers of children with FXS. The mothers differed in their use of gestures and redirecting the child's attention. Overall, mothers in both groups of children appeared to adapt appropriately to their children's developmental needs.

Preeclampsia complicated by advanced maternal age: a registry-based study on primiparous women in Finland 1997–2008

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Lamminpää Reeta

2012-06-01

Full Text Available Abstract Background Preeclampsia is a frequent syndrome and its cause has been linked to multiple factors, making prevention of the syndrome a continuous challenge. One of the suggested risk factors for preeclampsia is advanced maternal age. In the Western countries, maternal age at first delivery has been steadily increasing, yet few studies have examined women of advanced maternal age with preeclampsia. The purpose of this registry-based study was to compare the obstetric outcomes in primiparous and preeclamptic women younger and older than 35 years. Methods The registry-based study used data from three Finnish health registries: Finnish Medical Birth Register, Finnish Hospital Discharge Register and Register of Congenital Malformations. The sample contained women under 35 years of age (N = 15,437 compared with those 35 and over (N = 2,387 who were diagnosed with preeclampsia and had their first singleton birth in Finland between 1997 and 2008. In multivariate modeling, the main outcome measures were Preterm delivery (before 34 and 37 weeks, low Apgar score (5 min., small-for-gestational-age, fetal death, asphyxia, Cesarean delivery, induction, blood transfusion and admission to a Neonatal Intensive Care Unit. Results Women of advanced maternal age (AMA exhibited more preeclampsia (9.4% than younger women (6.4%. They had more prior terminations (25 ( Conclusions Preeclampsia is more common in women with advanced maternal age. Advanced maternal age is an independent risk factor for adverse outcomes in first-time mothers with preeclampsia.

Sirenomelia (Mermaid syndrome in an infant of a diabetic mother

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Davari Tanha F

2003-05-01

Full Text Available Caudal regression syndrome (Caudal dysplasia sequence is a rare congenital malformation. It has a spectrum ranging from simple anal atresia to the absence of sacral, lumbar and possibly lower thoracic vertebrae and the most severe form called sirenomelia (Mermaid syndrome. Sirenomelia has a sole characteristic, which is the limbs fusion, with multiple internal structural abnormalities particularly in the renal tract (bilateral renal agenesis. This is a rare condition with a relative risk of 200-250 in diabetic pregnancies. The etiology of this syndrome is not well known. Maternal diabetes in considered to be other possible factors. We present birth of an infant with great congenital defect, which was categorized as the most intense form of caudal regression syndrome (sirenomelia. The baby was born from an uncontrolled diabetic mother who was ignorant of her diabetes. She had a sonographic report at early third-trimester of pregnancy, which had shown severe oligohydramnios and according to this reason the anomaly of the fetus was not detected at that time (antenatal. Since sirenomelia is a lethal abnormality, the infant died a few hours after birth. As notes above caudal regression syndrome is strongly associated with maternal diabetes; due to metabolic derangement in uncontrolled serum glucose.

Maternal smoking during pregnancy increases the risk of postnatal infections in preterm neonates

DEFF Research Database (Denmark)

Jeppesen, Dorthe Lisbeth; Nielsen, Susanne Dam; Ersbøll, Annette Kjær

2008-01-01

Background: Maternal smoking during pregnancy is known to be associated with perinatal complications such as preterm delivery, low birth weight, and sudden infant death syndrome. Objective: The purpose of this study was to evaluate the influence of smoking during pregnancy on the risk of postnata...

Placental vascular pathology and increased thrombin generation as mechanisms of disease in obstetrical syndromes

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Salvatore Andrea Mastrolia

2014-11-01

Full Text Available Obstetrical complications including preeclampsia, fetal growth restriction, preterm labor, preterm prelabor rupture of membranes and fetal demise are all the clinical endpoint of several underlying mechanisms (i.e., infection, inflammation, thrombosis, endocrine disorder, immunologic rejection, genetic, and environmental, therefore, they may be regarded as syndromes. Placental vascular pathology and increased thrombin generation were reported in all of these obstetrical syndromes. Moreover, elevated concentrations of thrombin-anti thrombin III complexes and changes in the coagulation as well as anticoagulation factors can be detected in the maternal circulation prior to the clinical development of the disease in some of these syndromes. In this review, we will assess the changes in the hemostatic system during normal and complicated pregnancy in maternal blood, maternal–fetal interface and amniotic fluid, and describe the contribution of thrombosis and vascular pathology to the development of the great obstetrical syndromes.

Neonatal opioid withdrawal syndrome.

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Sutter, Mary Beth; Leeman, Lawrence; Hsi, Andrew

2014-06-01

Neonatal opioid withdrawal syndrome is common due to the current opioid addiction epidemic. Infants born to women covertly abusing prescription opioids may not be identified as at risk until withdrawal signs present. Buprenorphine is a newer treatment for maternal opioid addiction and appears to result in a milder withdrawal syndrome than methadone. Initial treatment is with nonpharmacological measures including decreasing stimuli, however pharmacological treatment is commonly required. Opioid monotherapy is preferred, with phenobarbital or clonidine uncommonly needed as adjunctive therapy. Rooming-in and breastfeeding may decease the severity of withdrawal. Limited evidence is available regarding long-term effects of perinatal opioid exposure. Copyright © 2014 Elsevier Inc. All rights reserved.

Meckel Syndrome: Genetics, Perinatal Findings, and Differential Diagnosis

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Chih-Ping Chen

2007-03-01

Full Text Available Meckel syndrome (MKS is a lethal, autosomal recessive disorder characterized by occipital encephalocele, bilateral renal cystic dysplasia, hepatic ductal proliferation, fibrosis and cysts, and polydactyly. Genetic heterogeneity of MKS has been established by three reported MKS loci, i.e., MKS1 on 17q23, MKS2 on 11q13, and MKS3 on 8q21.13-q22.1. MKS1 encodes a component of flagellar apparatus basal body proteome, which is associated with ciliary function. MKS3 encodes a seven-transmembrane receptor protein, meckelin. The identification of the MKS3 gene as well as the MKS1 gene enables molecular genetic testing for at-risk families, and allows accurate genetic counseling, carrier testing, and prenatal diagnosis. Pregnancies with MKS fetuses may be associated with an elevated maternal serum α-fetoprotein level and an abnormal screening result in the second-trimester maternal serum screening test. The classic MKS triad of occipital encephalocele, postaxial polydactyly, and bilateral enlarged multicystic kidneys can be diagnosed before the 14th gestational weeks by ultrasonography. However, later in pregnancy, severe oligohydramnios may make the diagnosis of polydactyly and encephalocele difficult. Differential diagnosis for MKS includes autosomal recessive polycystic kidney disease, trisomy 13, Smith-Lemli-Opitz syndrome, hydrolethalus syndrome, Senior-Loken syndrome, Joubert syndrome, Bardet-Biedl syndrome, and oral-facial-digital syndrome type 1. This article provides an overview of genetics, perinatal findings, and differential diagnosis of MKS. The ciliopathy underlies the pathogenesis of MKS. Prenatal diagnosis of bilateral enlarged multicystic kidneys should alert MKS and prompt a thorough investigation of central nervous system malformations and polydactyly.

Antenatal Bartter Syndrome: A Review

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Y. Ramesh Bhat

2012-01-01

Full Text Available Antenatal Bartter syndrome (ABS is a rare autosomal recessive renal tubular disorder. The defective chloride transport in the loop of Henle leads to fetal polyuria resulting in severe hydramnios and premature delivery. Early onset, unexplained maternal polyhydramnios often challenges the treating obstetrician. Increasing polyhydramnios without apparent fetal or placental abnormalities should lead to the suspicion of this entity. Biochemical analysis of amniotic fluid is suggested as elevated chloride level is usually diagnostic. Awareness, early recognition, maternal treatment with indomethacin, and amniocentesis allow the pregnancy to continue. Affected neonates are usually born premature, have postnatal polyuria, vomiting, failure to thrive, hypercalciuria, and subsequently nephrocalcinosis. Hypokalemia, metabolic alkalosis, secondary hyperaldosteronism and hyperreninaemia are other characteristic features. Volume depletion due to excessive salt and water loss on long term stimulates renin-angiotensin-aldosterone system resulting in juxtaglomerular hyperplasia. Clinical features and electrolyte abnormalities may also depend on the subtype of the syndrome. Prenatal diagnosis and timely indomethacin administration prevent electrolyte imbalance, restitute normal growth, and improve activity. In this paper, authors present classification, pathophysiology, clinical manifestations, laboratory findings, complications, and prognosis of ABS.

Antenatal Bartter Syndrome: A Review

Science.gov (United States)

Bhat, Y. Ramesh; Vinayaka, G.; Sreelakshmi, K.

2012-01-01

Antenatal Bartter syndrome (ABS) is a rare autosomal recessive renal tubular disorder. The defective chloride transport in the loop of Henle leads to fetal polyuria resulting in severe hydramnios and premature delivery. Early onset, unexplained maternal polyhydramnios often challenges the treating obstetrician. Increasing polyhydramnios without apparent fetal or placental abnormalities should lead to the suspicion of this entity. Biochemical analysis of amniotic fluid is suggested as elevated chloride level is usually diagnostic. Awareness, early recognition, maternal treatment with indomethacin, and amniocentesis allow the pregnancy to continue. Affected neonates are usually born premature, have postnatal polyuria, vomiting, failure to thrive, hypercalciuria, and subsequently nephrocalcinosis. Hypokalemia, metabolic alkalosis, secondary hyperaldosteronism and hyperreninaemia are other characteristic features. Volume depletion due to excessive salt and water loss on long term stimulates renin-angiotensin-aldosterone system resulting in juxtaglomerular hyperplasia. Clinical features and electrolyte abnormalities may also depend on the subtype of the syndrome. Prenatal diagnosis and timely indomethacin administration prevent electrolyte imbalance, restitute normal growth, and improve activity. In this paper, authors present classification, pathophysiology, clinical manifestations, laboratory findings, complications, and prognosis of ABS. PMID:22518185

Cardiovascular causes of maternal sudden death. Sudden arrhythmic death syndrome is leading cause in UK.

Science.gov (United States)

Krexi, Dimitra; Sheppard, Mary N

2017-05-01

This study aims to determine the causes of sudden cardiac death during pregnancy and in the postpartum period and patients' characteristics. There are few studies in the literature. Eighty cases of sudden unexpected death due to cardiac causes in relation to pregnancy and postpartum period in a database of 4678 patients were found and examined macroscopically and microscopically. The mean age was 30±7 years with a range from 16 to 43 years. About 30% were 35 years old or older; 50% of deaths occurred during pregnancy and 50% during the postpartum period. About 59.18% were obese or overweight where body mass index data were available. The leading causes of death were sudden arrhythmic death syndrome (SADS) (53.75%) and cardiomyopathies (13.80%). Other causes include dissection of aorta or its branches (8.75%), congenital heart disease (2.50%) and valvular disease (3.75%). This study highlights sudden cardiac death in pregnancy or in the postpartum period, which is mainly due to SADS with underlying channelopathies and cardiomyopathy. We wish to raise awareness of these frequently under-recognised entities in maternal deaths and the need of cardiological screening of the family as a result of the diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of ethanol consumption during gestation on maternal-fetal amino acid metabolism in the rat

International Nuclear Information System (INIS)

Lin, G.W.

1981-01-01

The distribution of 14 C-alpha-aminoisobutyric acid (AIB), administered intravenously, in maternal, fetal and placental tissues was examined in the rat on gestation-day 21. Ethanol consumption during gestation (day 6 through 21) significantly reduced the uptake of AIB by the placenta and fetus while exerting no influence on maternal tissue AIB uptake. The concentration of fetal plasma free histidine was decreased 50% as a result of maternal ethanol ingestion, but the free histidine level of maternal plasma was not altered. Since no effect on protein content of fetal tissue could be detected, it is speculated that reduced histidine to the fetus might significantly alter the amounts of histamine and carnosine formed via their precursor. The significance of these findings in relation to the Fetal Alcohol Syndrome is discussed

Maternal Sensitivity and Overt Aggression in Young Children with Down Syndrome

Science.gov (United States)

Niccols, Alison; Milligan, Karen; Chisholm, Vivienne; Atkinson, Leslie

2011-01-01

Children with genetic syndromes offer a unique opportunity to combine genetic and environmental approaches to the study of aggression. Children with genetic syndromes associated with developmental delay are at increased risk for behavior problems, but little is known about risk and resilience factors. In this study, we examined maternal…

Zika Virus Infection in Pregnancy, Microcephaly, and Maternal and Fetal Health: What We Think, What We Know, and What We Think We Know.

Science.gov (United States)

Alvarado, Maria Gabriela; Schwartz, David A

2017-01-01

-The global epidemic of Zika virus (ZIKV) infection has emerged as an important public health problem affecting pregnant women and their infants. -To review the causal association between ZIKV infection during pregnancy and intrauterine fetal infection, microcephaly, brain damage, congenital malformation syndrome, and experimental laboratory models of fetal infection. Many questions remain regarding the risk factors, pathophysiology, epidemiology, and timing of maternal-fetal transmission and disease. These include mechanisms of fetal brain damage and microcephaly; the role of covariables, such as viral burden, duration of viremia, and host genetics, on vertical transmission; and the clinical and pathologic spectrum of congenital Zika syndrome. Additional questions include defining the potential long-term physical and neurobehavioral outcomes for infected infants, whether maternal or fetal host genetics influence the clinical outcome, and whether ZIKV infection can cause maternal morbidity. Finally, are experimental laboratory and animal models of ZIKV infection helpful in addressing maternal-fetal viral transmission and the development of congenital microcephaly? This communication provides current information and attempts to address some of these important questions. -Comprehensive review of published scientific literature. -Recent advances in epidemiology, clinical medicine, pathology, and experimental studies have provided a great amount of new information regarding vertical ZIKV transmission and the mechanisms of congenital microcephaly, brain damage, and congenital Zika syndrome in a relatively short time. However, much work still needs to be performed to more completely understand the maternal and fetal aspects of this new and emerging viral disease.

The Role of Maternal-Fetal Cholesterol Transport in Early Fetal Life : Current Insights

NARCIS (Netherlands)

Baardman, Maria E.; Kerstjens-Frederikse, Wilhelmina S.; Berger, Rolf M. F.; Bakker, Marian K.; Hofstra, Robert M. W.; Plosch, Torsten

The importance of maternal cholesterol as an exogenous cholesterol source for the growing embryo was first reported in studies of Smith-Lemli-Opitz syndrome. Although most of the fetus's cholesterol is synthesized by the fetus itself, there is now growing evidence that during the first weeks of

The role of maternal-fetal cholesterol transport in early fetal life: Current insights

NARCIS (Netherlands)

T. Baardman (Taco); W.S. Kerstjens-Frederikse (Wilhelmina); R.M.F. Berger (Rolf); M.K. Bakker (Marian); R.M.W. Hofstra (Robert); T. Plösch (Torsten)

2013-01-01

textabstractThe importance of maternal cholesterol as an exogenous cholesterol source for the growing embryo was first reported in studies of Smith-Lemli-Opitz syndrome. Although most of the fetus's cholesterol is synthesized by the fetus itself, there is now growing evidence that during the first

Distribution of maternal age and birth order groups in cases with unclassified multiple congenital abnormalities according to the number of component abnormalities: a national population-based case-control study.

Science.gov (United States)

Csermely, Gyula; Czeizel, Andrew E; Veszprémi, Béla

2015-02-01

Multiple congenital abnormalities are caused by chromosomal aberrations, mutant major genes and teratogens. A minor proportion of these patients are identified as syndromes but the major part belonging to the group of unclassified multiple CAs (UMCAs). The main objective of this study was to evaluate the maternal age and birth order in pregnant women who had offspring affected with UMCA. The strong association between numerical chromosomal aberrations, e.g., Down syndrome and advanced maternal age is well-known and tested here. The Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980 to 1996, yielded a large population-based national data set with 22,843 malformed newborns or fetuses ("informative cases") included 1349 UMCA cases with their 2407 matched controls. Case-control comparison of maternal age and birth order was made for cases with UMCA, stratified by component numbers and their controls. In addition, 834 cases with Down syndrome were compared to 1432 matched controls. The well-known advanced maternal age with the higher risk for Down syndrome was confirmed. The findings of the study suggest that the young age of mothers associates with the higher risk of UMCA, in addition birth order 4 or more associates with the higher risk for UMCA with 2 and 3 component CAs. This study was the first to analyze the possible maternal and birth order effect for cases with UMCA, and the young age and higher birth order associated with a higher risk for UMCA. © 2014 Wiley Periodicals, Inc.

Construction of HMI Network System for Individualized Maternity Intervention Service against Birth Defects in Community

Institute of Scientific and Technical Information of China (English)

Xu-huai HU

2007-01-01

The paper expounds the community maternity service system against birth defects,from the viewpoint of individualized service in family planning. We have utilized modern information technology to develop health management information (HMI) network with individualized maternity, and to establish the community service system for intervention of birth defects. The service system applied the concept of modern health management information to implementing informational management for screening,treatment, following up, outcome monitoring, so as to provide a base for promotion of health, diagnosis, treatment as well as scientific research, with the prenatal screening of Down's syndrome as a model. The introduction to informational network during the processes of service has been carried out with regards to its composition, function and application, while introducing the effects of computerized case record individualized in prevention, management and research of Down's syndrome.

Effect of maternal PCOS and PCOS-like phenotype on the offspring’s health

Science.gov (United States)

Puttabyatappa, Muraly; Cardoso, Rodolfo C.; Padmanabhan, Vasantha

2015-01-01

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities affecting women of reproductive age. While the exact origin of PCOS is unknown, observations from clinical and animal studies suggest that maternal hyperandrogenism may be a contributing factor. Because women with PCOS manifest hyperandrogenism during pregnancy, changes in the gestational endocrine milieu may play a role in the vertical transmission of this syndrome. This review discusses the potential developmental origins of PCOS, the impact of maternal PCOS on the offspring’s health and contributions of the postnatal environment, capitalizing on findings from animal models that exhibit a PCOS-like phenotype. In addition, this review highlights the scarcity of data at early gestational stages in humans and the importance of animal experimentation to better understand the cellular and molecular mechanisms involved in the programming of adult diseases, therefore, helping identify therapeutic targets for preventive and treatment strategies. PMID:26639019

Breastfeeding Infants with Phenylketonuria in the United States and Canada

Science.gov (United States)

Press, Nancy; Knafl, Kathleen A.; Steiner, Robert D.; Houck, Gail M.

2014-01-01

Abstract Objective: This study described the prevalence and duration of mothers' breastfeeding infants with phenylketonuria (PKU) and explored factors related to duration of breastfeeding as a surrogate for breastfeeding success. Subjects and Methods: Descriptive analysis as performed from an international Internet survey of mothers (n=103) who met the inclusion criteria: (1) at least 21 years of age, (2) able to read and write in English, (3) child with PKU, and (4) living in the United States or Canada. Results: Of the 103 mothers, 89 (86%) initiated breastfeeding immediately following delivery, whereas 14 (14%) chose bottle feeding. In comparison to breastfeeding after delivery, significantly fewer mothers breastfed after diagnosis (McNemar's χ2=30.33, p<0.001; n=72 vs. n=89). Breastfeeding duration ranged from less than 1 month to 24 months with one modal duration category (n=20, 22%) at less than 1 month. The timing of the addition of commercial infant formula to supplement breastfeeding or expressed mothers' milk was associated with a shorter duration of breastfeeding among infants with PKU: χ2 (42, n=73)=88.13, p<0.001. Conclusions: PKU is treated with phenylalanine (Phe) restriction. Breastfeeding infants with PKU is challenging in part because Phe intake is difficult to determine precisely. We studied breastfeeding duration in infants with PKU and factors associated with success. Further research should identify the unique needs of mothers' breastfeeding infants with PKU to guide the development of interventions specific to these mothers to support their efforts to continue breastfeeding after the diagnosis of PKU. PMID:24350704

Insulin resistance in pregnant women with and without polycystic ovary syndrome, and measures of body composition in offspring at birth and three years of age.

Science.gov (United States)

Finnbogadóttir, Sara K; Glintborg, Dorte; Jensen, Tina K; Kyhl, Henriette B; Nohr, Ellen A; Andersen, Marianne

2017-11-01

Polycystic ovary syndrome is associated with obesity and insulin resistance in the non-pregnant state, but little is known about insulin sensitivity in the pregnant state. Our objective was to compare insulin resistance in pregnant women with and without polycystic ovary syndrome and explore the impact of polycystic ovary syndrome on body composition in offspring at birth and at three years of age. A prospective cohort study including 2548 live-born singleton mother-child pairs residing in Odense municipality, Denmark, during 2010-2013. Of the 2548 women, 241 (9.4%) had polycystic ovary syndrome. Homeostatic model assessment for insulin resistance assessments were comparable in women with and without polycystic ovary syndrome. However, the subgroup of overweight women with polycystic ovary syndrome had significantly higher levels of homeostatic model assessment for insulin resistance than overweight women without polycystic ovary syndrome (mean ± 2 SD): 4.4 (3.1) vs. 3.6 (3.4), p = 0.004. Maternal polycystic ovary syndrome did not affect offspring birthweight after accounting for age. However, polycystic ovary syndrome, adjusted for maternal body mass index, was associated with increased body mass index at three years of age (mean ± 2 SD): 16.0 (2.2) vs. 15.7 (2.1) kg/m 2 , p = 0.04. In our cohort, maternal polycystic ovary syndrome was not associated with insulin resistance after correcting for body mass index and was not an independent predictor of offspring birthweight. However, both polycystic ovary syndrome and high maternal body mass index may increase risk of childhood obesity at three years of age. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Maternal serum uric acid level and maternal and neonatal complications in preeclamptic women: A cross-sectional study.

Science.gov (United States)

Asgharnia, Maryam; Mirblouk, Fariba; Kazemi, Soudabeh; Pourmarzi, Davood; Mahdipour Keivani, Mina; Dalil Heirati, Seyedeh Fatemeh

2017-09-01

Preeclampsia is associated with maternal and neonatal complications. It has been indicated that increased uric acid might have a predictive role on preeclampsia. We aimed to investigate the relationship between the level of uric acid with maternal and neonatal complications in women with preeclampsia. In this cross-sectional study, 160 singleton preeclamptic women at more than 28 wk gestational age were included. Hemoglobin, hematocrit, platelet count, liver and uric acid tests, and maternal and neonatal complications were assessed. The severity of preeclampsia, placental abruption, preterm labor, thrombocytopenia, elevated alanine aminotransferase and aspartate aminotransferase (ALT and AST), HELLP syndrome, eclampsia and required hospitalization in the ICU was considered as the maternal complication. Fetal complications were: small for gestational age (SGA), intrauterine fetal death, hospitalization in the neonatal intensive care unit, and Apgar score uric acid in women with severe preeclampsia was significantly higher than non-severe preeclampsia (p=0.031), also in those with an abnormal liver test (p=0.009). The mean level of uric acid in women with preterm delivery was significantly higher than women with term delivery (p=0.0001). Also, the level of uric acid had no effect on neonatal hospitalization in neonate invasive care unit. Based on logistic regression, the incidence of severe preeclampsia not affected by decreased or increased serum levels of uric acid. With higher level of uric acid in server preeclampsia we can expected more complications such as hepatic dysfunction and preterm delivery. Thus serum uric acid measurement can be helpful marker for severe preeclampsia.

Massive parallel sequencing as a new diagnostic approach for phenylketonuria and tetrahydrobiopterin-deficiency in Thailand.

Science.gov (United States)

Chaiyasap, Pongsathorn; Ittiwut, Chupong; Srichomthong, Chalurmpon; Sangsin, Apiruk; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk

2017-09-16

Hyperphenylalaninemia (HPA) can be classified into phenylketonuria (PKU) which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, and BH4 deficiency caused by alterations in genes involved in tetrahydrobiopterin (BH4) biosynthesis pathway. Dietary restriction of phenylalanine is considered to be the main treatment of PKU to prevent irreversible intellectual disability. However, the same dietary intervention in BH4 deficiency patients is not as effective, as BH4 is also a cofactor in many neurotransmitter syntheses. We utilized next generation sequencing (NGS) technique to investigate four unrelated Thai patients with hyperphenylalaninemia. We successfully identified all eight mutant alleles in PKU or BH4-deficiency associated genes including three novel mutations, one in PAH and two in PTS, thus giving a definite diagnosis to these patients. Appropriate management can then be provided. This study identified three novel mutations in either the PAH or PTS gene and supported the use of NGS as an alternative molecular genetic approach for definite diagnosis of hyperphenylalaninemia, thus leading to proper management of these patients in Thailand.

Maternal uniparental disomy for chromosome 14 in a boy with a normal karyotype

NARCIS (Netherlands)

Hordijk, R; Scheffer, H; Leegte, B; Hofstra, RMW; Stolte-Dijkstra, [No Value

1999-01-01

Groningen, Ne report on a boy with a maternal uniparental disomy for chromosome 14 (UPD(14)). At 7 years of age he was referred to us by the paediatrician because of symptoms of Prader-Willi syndrome (PWS). He showed short stature, obesity, mild developmental delay, cryptorchidism, and some mild

The HELLP syndrome : Its association with unexplained elevation of MSAFP and MShCG in the second trimester

NARCIS (Netherlands)

Morssink, LP; Heringa, MP; Beekhuis, [No Value; DeWolf, BTHM; Mantingh, A

In this study, we examined the relationship between concentrations of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG) in the second trimester and the 'haemolysis, elevated liver enzymes, low platelet count' (HELLP) syndrome. The concentrations of both

Trends and geographic inequalities in the prevalence of Down syndrome in Europe, 1980-1999.

Science.gov (United States)

Dolk, H; Loane, M; Garne, E; De Walle, H; Queisser-Luft, A; De Vigan, C; Addor, M C; Gener, B; Haeusler, M; Jordan, H; Tucker, D; Stoll, C; Feijoo, M; Lillis, D; Bianchi, F

2005-11-01

EUROCAT is a network of population-based registries for the epidemiologic surveillance of congenital anomalies covering approximately one quarter of births in the European Union. Down syndrome constitutes approximately 8% of cases of registered congenital anomaly in Europe, with over 7000 affected pregnancies in the 15 current member states of the European Union each year. In this paper, we aim to examine trends in the live birth prevalence of Down syndrome in Europe in the light of trends in maternal age and in prenatal diagnosis. Descriptive analysis of data from 24 EUROCAT registries, covering 8.3 million births 1980-99. Cases include live births, stillbirths and terminations of pregnancy following prenatal diagnosis. Since 1980, the proportion of births to mothers of 35 years of age and over has risen quite dramatically from 8 to 14% for the European Union as a whole, with steeper rises in some regions. By 1995-1999, the proportion of "older" mothers varied between regions from 10% to 25%, and the total prevalence (including terminations of pregnancy) of Down syndrome varied from 1 to 3 per 1000 births. Some European regions have shown a more than twofold increase in total prevalence of Down syndrome since 1980. The proportion of cases of Down syndrome which were prenatally diagnosed followed by termination of pregnancy in 1995-1999 varied from 0% in the three regions of Ireland and Malta where termination of pregnancy is illegal, to less than 50% in 14 further regions, to 77% in Paris. The extent to which terminations of pregnancy were concen trated among older mothers varied between regions. The live birth prevalence has since 1980 increasingly diverged from the rising total prevalence, in some areas remaining approximately stable, in others decreasing over time. The rise in average maternal age in Europe has brought with it an increase in the number of pregnancies affected by Down syndrome. The widespread practice of prenatal screening and termination of

Maternal analgosedation and breastfeeding: guidance for the pediatrician

Directory of Open Access Journals (Sweden)

Karel Allegaert

2015-03-01

Full Text Available As part of analgosedative treatment modalities after delivery (e.g. caesarean related pain, birth related trauma, pre-existing pain syndromes, mothers are treated with different analgosedatives that may also affect the nursing infant. This review aims to summarize the available knowledge on commonly prescribed analgosedatives (opioids, intravenous and inhalational anesthetics, benzodiazepines, non-opioid analgesics, and local anesthetics during breastfeeding. We propose that the use of systemic non-opioid analgesics, local anesthetics, inhalational or intravenous anesthetics is safe when mothers are nursing. When systemic opioids are used, we recommend pediatricians to consider clinical monitoring of the infant for sedation. The duration of maternal exposure (> 4 days and the presence of maternal signs of somnolence are hereby of additional relevance. We encourage research groups to report on their specific observations and expertise in order to further validate the current practices and guidance.

Role for Genetic Anticipation in Lynch Syndrome

DEFF Research Database (Denmark)

Nilbert, Mef; Timshel, Susanne; Bernstein, Inge

2009-01-01

PURPOSE: Anticipation (ie, an earlier age at onset in successive generations) is linked to repeat expansion in neurodegenerative syndromes, whereas its role in hereditary cancer is unclear. We assessed anticipation in Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), in which DNA...... mismatch repair (MMR) defects cause early and accelerated tumor development with a broad tumor spectrum. PATIENTS AND METHODS: In the population-based Danish HNPCC registry, 407 MMR gene mutation carriers who had developed cancer associated with Lynch syndrome, were identified. These individuals formed 290....... The effect remained when cancers diagnosed at surveillance were excluded, applied to maternal as well as paternal inheritance, and was independent of the MMR gene mutated. CONCLUSION: The effect from anticipation demonstrated in this large, population-based Lynch syndrome cohort underscores the need...

Epigenetic and developmental influences on the risk of obesity, diabetes, and metabolic syndrome

Directory of Open Access Journals (Sweden)

Smith CJ

2015-06-01

Full Text Available Caitlin J Smith, Kelli K Ryckman Department of Epidemiology, University of Iowa, College of Public Health, Iowa City, IA, USA Abstract: Metabolic syndrome is a growing cause of morbidity and mortality worldwide. Metabolic syndrome is characterized by the presence of a variety of metabolic disturbances including obesity, hyperlipidemia, hypertension, and elevated fasting blood sugar. Although the risk for metabolic syndrome has largely been attributed to adult lifestyle factors such as poor nutrition, lack of exercise, and smoking, there is now strong evidence suggesting that predisposition to the development of metabolic syndrome begins in utero. First posited by Hales and Barker in 1992, the “thrifty phenotype” hypothesis proposes that susceptibility to adult chronic diseases can occur in response to exposures in the prenatal and perinatal periods. This hypothesis has been continually supported by epidemiologic studies and studies involving animal models. In this review, we describe the structural, metabolic and epigenetic changes that occur in response to adverse intrauterine environments including prenatal and postnatal diet, maternal obesity, and pregnancy complications. Given the increasing prevalence of metabolic syndrome in both the developed and developing worlds, a greater understanding and appreciation for the role of the intrauterine environment in adult chronic disease etiology is imperative. Keywords: epigenetics, metabolic syndrome, fetal programming, maternal, pregnancy complications

Access to treatment for phenylketonuria by judicial means in Rio Grande do Sul, Brazil

Directory of Open Access Journals (Sweden)

Luciano Mangueira Trevisan

2015-05-01

Full Text Available Treatment of phenylketonuria (PKU includes the use of a metabolic formula which should be provided free of charge by the Unified Health System (SUS. This retrospective, observational study sought to characterize judicial channels to obtain PKU treatment in Rio Grande do Sul (RS, Brazil. Lawsuits filed between 2001- 2010 and having as beneficiaries PKU patients requesting treatment for the disease were included. Of 20 lawsuits filed, corresponding to 16.8% of RS patients with PKU, 19 were retrieved for analysis. Of these, only two sought to obtain therapies other than metabolic formula. In all the other 17 cases, prior treatment requests had been granted by the State Department of Health. Defendants included the State (n = 19, the Union (n = 1, and municipalities (n = 4. In 18/19 cases, the courts ruled in favor of the plaintiffs. Violation of the right to health and discontinuation of State-provided treatment were the main reasons for judicial recourse. Unlike other genetic diseases, patients with PKU seek legal remedy to obtain a product already covered by the national pharmaceutical assistance policy, suggesting that management failures are a driving factor for judicialization in Brazil.

Genotype-Phenotype Correlation of Maternally Inherited Disorders due to Mutations in Mitochondrial DNA

Directory of Open Access Journals (Sweden)

Peterus Thajeb

2006-09-01

Full Text Available Mitochondrial disorders are heterogeneous systemic ailments that are most often caused by maternal inheritance of a variety of mutations of the mitochondrial (mt DNA. Paternal inheritance and somatic mutation are rare. The disorders are well recognized not only for the genotypic heterogeneity, but also the phenotypic variation among the affected members of a single family. The genotype-phenotype correlation of the diversity of the syndromic and non-syndromic features of mitochondrial disorders are discussed. Some aspects of the molecular mechanisms of this heterogeneity, and the histopathologic findings are highlighted.

Magnetic resonance imaging of the brain in phenylketonuria

International Nuclear Information System (INIS)

Izumi, Mina; Yamazaki, Hirotaka; Nakabayashi, Hiroki; Owada, Misao

2006-01-01

To investigate the correlation between the abnormalities of magnetic resonance imaging (MRI) of the brain and blood phenylalanine (Phe) levels in phenylketonuria (PKU) and hyperphenylalaninemia (HPA), we reviewed MRIs from 16 patients with early treated PKU and HPA. Their ages ranged from 4-24 years and were found by mass screening and treated from early infancy, and 5 patients with late detected PKU who were aged 24-33 years. The former patients had no remarkable neurological signs or symptoms. One patient of the latter had severe mental retardation and 3 patients had mild to border mental retardation. Axial T 1 -weighted and T 2 -weighted spin echo sequences, fluid attenuated inversion recovery MR sequences (FLAIR) through the brain were performed. The scans were graded according to the extent of increased signal intensity of white matter on T 2 -weighted and FLAIR sequences. To investigate the influence of plasma Phe levels, three approaches were used. Firstly an average of all yearly serial blood Phe concentration was calculated for each patient, then Phe was determined for a period of 6 months and 12 months prior to MRI, and also for their lifetime up to their age at the time this study began. These average blood Phe levels were classified into four categories: group A: Phe level below 5 mg/dl, group B: 5-8 mg/dl, group C: 9-12 mg/dl, group D: above 12 mg/dl. MRI findings were not significant in group A. Remarkable high signals of white matter were obtained in group C and D, except for one patient in group D whose MRI finding was normal. MRI findings correlated to long-term dietary control stronger than those of 6 months prior to MRI. The clinical significance of MRI abnormalities is still unclear, and further study is required to clarify the relationship of the MRI findings and clinical conditions. (author)

Relationship between Maternal Language Parameters and the Child's Language Competency and Developmental Condition.

Science.gov (United States)

Hooshyar, Nahid T.

Maternal language directed to 21 nonhandicapped, 21 Down syndrome, and 19 language impaired preschool children was examined. The three groups (all Caucasian and middle-class) were matched in mean length of utterance (MLU) and in developmental skills as measured on the Vineland Adaptive Behavior Scale. Mother-child language interaction was…

Evaluation and interpretation of maternal toxicity in Segment II studies: Issues, some answers, and data needs

International Nuclear Information System (INIS)

Rogers, John M.; Chernoff, Neil; Keen, Carl L.; Daston, George P.

2005-01-01

Biologically rational regulatory policies with regards to developmental toxicity are often based on the extrapolation of standard laboratory rodent bioassay results to the human population. Significantly contributing to the difficulty of this task is the possibility that general toxic effects on the maternal organism may affect the developing conceptus. This review examines maternal factors which may bear directly or indirectly upon developmental outcome, with emphasis on those of greatest relevance to the hazard assessment process. Standard teratology testing protocols call for top dosage levels that induce overt maternal toxicity, and the developmental effects of this toxicity (both alone, and with concurrent embryo/fetal insult) continue to present regulators with considerable interpretive difficulties. In response to these problems, there have been both research and literature review efforts dealing with the relationship of maternal and developmental toxicity. Maternally mediated developmental toxicity occurs with a number of agents, and toxicant-induced alterations in maternal physiology may affect the conceptus at dosages not causing overt maternal toxicity. Relevant studies are reviewed here, and suggestions for avenues of future research are offered including the identification of any syndromes of developmental effects occurring at maternally toxic levels irrespective of the causative agent, and experimental approaches for the characterization of maternal toxicity

Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing

Science.gov (United States)

Pinheiro de Oliveira, Felipe; Mendes, Roberta Hack; Dobbler, Priscila Thiago; Mai, Volker; Pylro, Victor Salter; Waugh, Sheldon G; Vairo, Filippo; Refosco, Lilia Farret; Schwartz, Ida Vanessa Doederlein

2016-01-01

Phenylketonuria (PKU) is an inborn error of metabolism associated with high blood levels of phenylalanine (Phe). A Phe-restricted diet supplemented with L-amino acids is the main treatment strategy for this disease; if started early, most neurological abnormalities can be prevented. The healthy human gut contains trillions of commensal bacteria, often referred to as the gut microbiota. The composition of the gut microbiota is known to be modulated by environmental factors, including diet. In this study, we compared the gut microbiota of 8 PKU patients on Phe-restricted dietary treatment with that of 10 healthy individuals. The microbiota were characterized by 16S rRNA sequencing using the Ion Torrent™ platform. The most dominant phyla detected in both groups were Bacteroidetes and Firmicutes. PKU patients showed reduced abundance of the Clostridiaceae, Erysipelotrichaceae, and Lachnospiraceae families, Clostridiales class, Coprococcus, Dorea, Lachnospira, Odoribacter, Ruminococcus and Veillonella genera, and enrichment of Prevotella, Akkermansia, and Peptostreptococcaceae. Microbial function prediction suggested significant differences in starch/glucose and amino acid metabolism between PKU patients and controls. Together, our results suggest the presence of distinct taxonomic groups within the gut microbiome of PKU patients, which may be modulated by their plasma Phe concentration. Whether our findings represent an effect of the disease itself, or a consequence of the modified diet is unclear. PMID:27336782

Fluctuations in phenylalanine concentrations in phenylketonuria: a review of possible relationships with outcomes.

Science.gov (United States)

Cleary, Maureen; Trefz, Friedrich; Muntau, Ania C; Feillet, François; van Spronsen, Francjan J; Burlina, Alberto; Bélanger-Quintana, Amaya; Giżewska, Maria; Gasteyger, Christoph; Bettiol, Esther; Blau, Nenad; MacDonald, Anita

2013-12-01

Fluctuations in blood phenylalanine concentrations may be an important determinant of intellectual outcome in patients with early and continuously treated phenylketonuria (PKU). This review evaluates the studies on phenylalanine fluctuations, factors affecting fluctuations, and if stabilizing phenylalanine concentrations affects outcomes, particularly neurocognitive outcome. Electronic literature searches of Embase and PubMed were performed for English-language publications, and the bibliographies of identified publications were also searched. In patients with PKU, phenylalanine concentrations are highest in the morning. Factors that can affect phenylalanine fluctuations include age, diet, timing and dosing of protein substitute and energy intake, dietary adherence, phenylalanine hydroxylase genotype, changes in dietary phenylalanine intake and protein metabolism, illness, and growth rate. Even distribution of phenylalanine-free protein substitute intake throughout 24h may reduce blood phenylalanine fluctuations. Patients responsive to and treated with 6R-tetrahydrobiopterin seem to have less fluctuation in their blood phenylalanine concentrations than controls. An increase in blood phenylalanine concentration may result in increased brain and cerebrospinal fluid phenylalanine concentrations within hours. Although some evidence suggests that stabilization of blood phenylalanine concentrations may have benefits in patients with PKU, more studies are needed to distinguish the effects of blood phenylalanine fluctuations from those of poor metabolic control. © 2013.

Correlation between genotype and the tetrahydrobiopterin-responsive phenotype in Chinese patients with phenylketonuria.

Science.gov (United States)

Tao, Jing; Li, Nana; Jia, Haitao; Liu, Zhen; Li, Xiaohong; Song, Jiaping; Deng, Ying; Jin, Xi; Zhu, Jun

2015-12-01

A growing body of research has suggested that tetrahydrobiopterin (BH4) responsive phenotype can be predicted by the phenylalanine hydroxylase (PAH) genotype in patients with phenylketonuria (PKU), but data concerning the association between genotype and BH4 responsiveness are scarce in China. A total of 165 PKU patients from China who had undergone a 24-h loading test with BH4 administration were recruited. Genotyping was performed by the next-generation sequencing (NGS) technique. Using the predicted residual PAH activity, we analyzed the association between genotype and BH4-responsiveness. Among the 165 patients, 40 patients (24.24%) responded to BH4. A total of 74 distinct mutations were observed, including 13 novel mutations. The mutation p.R241C was most frequently associated with response. Two known mutations (p.A322T and p.Q419R) and two novel mutations (p.L98V and IVS3-2A>T) were first reported as responsive to BH4. Residual PAH activity of at least 12.5% was needed for responsive genotypes. Genotype-based predictions of BH4-responsiveness are only for selecting potential responders. Accordingly, it is necessary to test potential responders with a long-term BH4 challenge.

Angelman syndrome, cause of epilepsy in infants

International Nuclear Information System (INIS)

Sykora, P.; Vicenova, A.; Svecova, L.; Kolnikova, M.

2014-01-01

Several chromosomal syndromes include brain dysfunction symptoms as mental retardation, developmental speech disorders and epilepsy. Authors present a case report of Angelman syndrome – neuro behavioral disorder associated with deletion in the maternal chromosome 15q 11-g13 causing mutation of the UBE3A gene. The main features consist of psychomotor retardation, developmental speech disorder, ataxia, tremor, hyperactivity, clapping hands, inadequate laughter and happiness, attention deficit and epilepsy. The later starts before the 3rd year of age in form of atypical absences, myoclonic and generalized tonic-clonic seizures. EEG typically shows episodes of slow activity with sharp waves occipitally. Prognosis is poor. Genetic syndromes importantly contribute to the etiology of epilepsy with early seizures. (author)

Pregnancy and Marfan syndrome

Science.gov (United States)

Goland, Sorel

2017-01-01

Pregnancy in women with Marfan syndrome (MFS) presents challenges to the clinician and the patient due to the increased incidence of maternal complications and involvement of the fetus, and deserves special consideration. The leading cause of morbidity and mortality in MFS is aortic dissection. This article presents an extensive review of available clinical information and provides recommendations for the management of patients with MFS during pregnancy. PMID:29270376

Severe hydramnios and preterm delivery in association with transient maternal diabetes insipidus.

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Weinberg, Lori E; Dinsmoor, Mara J; Silver, Richard K

2010-08-01

Diabetes insipidus is rare in pregnancy. It is characterized by hypoosmolar polyuria and may be central, nephrogenic, or transient in etiology; the latter is presumably related to excess placental vasopresinase production. In theory, fetal effects of this endocrine condition may include hydramnios secondary to fetal polyuria. A pregnant patient developed rapid-onset second-trimester hydramnios that prompted a thorough fetal and maternal evaluation. She ultimately was diagnosed with transient diabetes insipidus of pregnancy because of an abrupt change in her voiding pattern at 20 weeks of gestation, significant polydipsia, and laboratory studies that revealed a hypoosmolar polyuria with normal serum and urine electrolytes. Transient neonatal polyuria also was confirmed in association with this unique maternal endocrine syndrome. The most likely cause of hydramnios in this case is transient maternal diabetes insipidus of pregnancy from excessive secretion of placental vasopressinase resulting in fetal polyuria. In cases of hydramnios of unknown etiology, if a history of maternal polyuria is elicited and confirmed, diabetes insipidus of pregnancy may play a role in some cases.

Optimal management of phenylketonuria: a centralized expert team is more successful than a decentralized model of care.

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Camfield, Carol S; Joseph, Marissa; Hurley, Teresa; Campbell, Karen; Sanderson, Susan; Camfield, Peter R

2004-07-01

To compare phenylketonuria (PKU) management by a centralized, expert team in the Province of Nova Scotia (NS) with the decentralized approach in New Brunswick (NB). Retrospective chart review documented frequency of outpatient visits, phenylalanine (Phe) concentration, and medical formula use. Structured telephone interviews with the 8 regional NB dietitians (NB-D) documented their knowledge and support in PKU management. Patients with PKU (n=108; age, birth to 42 years) reside in NB (n=69) and NS (n=39). More were lost to contact in NB than in NS (9/69 vs 1/39) and more were completely off diet in NB than in NS (24/60 vs 1/38, P=.05). All 15 children 95% in NS. Mental handicap or borderline intelligence was common in both NB (44%) and NS (42%). All NB-D wished additional specialized medical, nursing, or social work assistance. PKU management appears to be more effective with an expert, coordinated team approach.

Life Satisfaction Among Mothers of Individuals with Prader-Willi Syndrome.

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Shivers, Carolyn M; Leonczyk, Caroline L; Dykens, Elisabeth M

2016-06-01

Mothers of individuals with Prader-Willi syndrome (PWS) often experience numerous stressors, even when compared to mothers of children with other intellectual and developmental disabilities. Despite this, these mothers show great variability in self-reported life satisfaction. Using data from a longitudinal study of individuals with PWS and their families, the present study analyzed factors related to maternal life satisfaction, both cross-sectionally and over time. Results show that both child factors (e.g., behavior problems, hyperphagia) and maternal factors (e.g., stress, coping style) were significantly related to maternal life satisfaction. However, none of the tested variables predicted change in life satisfaction over time. Research and practice implications are discussed.

Maternal anxiety versus depressive disorders: specific relations to infants' crying, feeding and sleeping problems.

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Petzoldt, J; Wittchen, H-U; Einsle, F; Martini, J

2016-03-01

Maternal depression has been associated with excessive infant crying, feeding and sleeping problems, but the specificity of maternal depression, as compared with maternal anxiety remains unclear and manifest disorders prior to pregnancy have been widely neglected. In this prospective longitudinal study, the specific associations of maternal anxiety and depressive disorders prior to, during and after pregnancy and infants' crying, feeding and sleeping problems were investigated in the context of maternal parity. In the Maternal Anxiety in Relation to Infant Development (MARI) Study, n = 306 primiparous and multiparous women were repeatedly interviewed from early pregnancy until 16 months post partum with the Composite International Diagnostic Interview for Women (CIDI-V) to assess DSM-IV anxiety and depressive disorders. Information on excessive infant crying, feeding and sleeping problems was obtained from n = 286 mothers during postpartum period via questionnaire and interview (Baby-DIPS). Findings from this study revealed syndrome-specific risk constellations for maternal anxiety and depressive disorders as early as prior to pregnancy: Excessive infant crying (10.1%) was specifically associated with maternal anxiety disorders, especially in infants of younger and lower educated first-time mothers. Feeding problems (36.4%) were predicted by maternal anxiety (and comorbid depressive) disorders in primiparous mothers and infants with lower birth weight. Infant sleeping problems (12.2%) were related to maternal depressive (and comorbid anxiety) disorders irrespective of maternal parity. Primiparous mothers with anxiety disorders may be more prone to anxious misinterpretations of crying and feeding situations leading to an escalation of mother-infant interactions. The relation between maternal depressive and infant sleeping problems may be better explained by a transmission of unsettled maternal sleep to the fetus during pregnancy or a lack of daily

Consequences of low birth weight, maternal illiteracy and poor access to medical care in rural India: infantile iatrogenic Cushing syndrome.

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Karande, Sunil

2015-08-21

Home delivery, low birth weight babies and maternal illiteracy among the poor in rural India are frequent. The rural poor prefer to seek healthcare from private providers, most of whom have no formal medical training and buy medicines from private pharmacies without a prescription owing to a weakly regulated environment. This report is of a 4-month-old baby from a remote village in northern India, who presented with exogenous Cushing syndrome. This baby was a full-term low birth weight home delivery. As the baby was not growing well, treatment was started at 1 month by a private doctor with betamethasone drops The mother on her own volition continued giving the betamethasone drops by buying the medicine over the counter from a private pharmacy. This case highlights the gaps in essential health services in rural India and the steps being taken to improve the situation. 2015 BMJ Publishing Group Ltd.

Maternal undernutrition and fetal developmental programming of obesity: the glucocorticoid connection.

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Correia-Branco, Ana; Keating, Elisa; Martel, Fátima

2015-02-01

An adequate maternal nutrition during pregnancy is crucial for the health outcome of offspring in adulthood. Maternal undernutrition during critical periods of fetal development can program the fetus for metabolic syndrome (MetS) later in life, especially when postnatally challenged with a hypernutritive diet. Adipogenesis, which begins in utero and accelerates in neonatal life, is a major candidate for developmental programming. During fetal development, the hypothalamic-pituitary-adrenal (HPA) axis is extremely susceptible to programming, and the HPA tone is increased throughout life in undernourished conditions. As a consequence, an alteration in the expression and function of glucocorticoid (GC) receptors and of the major GC regulatory enzymes (11β-hydroxysteroid dehydrogenase 1 and -2) occurs. In this review, we will give insights into the role of maternoplacental adverse interactions under the specific context of maternal undernutrition, for later-in-life MetS development, with a special emphasis on the role of GCs. © The Author(s) 2014.

Combined measurement of maternal serum FE3 and HPL for determination of fetus-placenta function

International Nuclear Information System (INIS)

Peng Yangshui; Li Gefang; Xia Dingwen

2003-01-01

Objective: To investigate the clinical application of combined measurement of maternal serum FE 3 and HPL for determination of fetus-placenta function. Methods: Maternal serum FE 3 and HPL levels were measured with RIA in 86 complicated and 39 non-complicated pregnant women. Results: Serum FE 3 contents in pregnant women complicated with hypertensive syndrome, intrauterine fetal distress, gestation above 33 wks complicated with diabetes and 3rd grade placenta were significantly lower than those in non-complicated ones (p 3 and HPL could improve the early diagnosis of high-risk pregnancies

The challenges of managing coexistent disorders with phenylketonuria: 30 cases.

Science.gov (United States)

MacDonald, A; Ahring, K; Almeida, M F; Belanger-Quintana, A; Blau, N; Burlina, A; Cleary, M; Coskum, T; Dokoupil, K; Evans, S; Feillet, F; Giżewska, M; Gokmen Ozel, H; Lotz-Havla, A S; Kamieńska, E; Maillot, F; Lammardo, A M; Muntau, A C; Puchwein-Schwepcke, A; Robert, M; Rocha, J C; Santra, S; Skeath, R; Strączek, K; Trefz, F K; van Dam, E; van Rijn, M; van Spronsen, F; Vijay, S

2015-12-01

The few published case reports of co-existent disease with phenylketonuria (PKU) are mainly genetic and familial conditions from consanguineous marriages. The clinical and demographic features of 30 subjects with PKU and co-existent conditions were described in this multi-centre, retrospective cohort study. Diagnostic age of PKU and co-existent condition, treatment regimen, and impact of co-existent condition on blood phenylalanine (Phe) control and PKU management were reported. 30 patients (11 males and 19 females), with PKU and a co-existent condition, current median age of 14 years (range 0.4 to 40 years) from 13 treatment centres from Europe and Turkey were described. There were 21 co-existent conditions with PKU; 9 were autoimmune; 6 gastrointestinal, 3 chromosomal abnormalities, and 3 inherited conditions. There were only 5 cases of parental consanguinity. Some patients required conflicting diet therapy (n=5), nutritional support (n=7) and 5 children had feeding problems. There was delayed diagnosis of co-existent conditions (n=3); delayed treatment of PKU (n=1) and amenorrhea associated with Grave's disease that masked a PKU pregnancy for 12 weeks. Co-existent conditions adversely affected blood Phe control in 47% (n=14) of patients. Some co-existent conditions increased the complexity of disease management and increased management burden for patients and caregivers. Occurrence of co-existent disease is not uncommon in patients with PKU and so investigation for co-existent disorders when the clinical history is not completely consistent with PKU is essential. Integrating care of a second condition with PKU management is challenging. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain MRI diffusion-weighted imaging in patients with classical phenylketonuria

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Manara, Renzo; Citton, Valentina; Carollo, Carla [University Hospital of Padua, Neuroradiologic Unit, Padua (Italy); Burlina, Alessandro P.; Ermani, Mario [University Hospital of Padua, Neurological Clinic, Department of Neuroscience, Padua (Italy); Vespignani, Francesco; Burlina, Alberto B. [University Hospital of Padua, Metabolic Diseases Unit, Department of Paediatrics, Padua (Italy)

2009-12-15

The aim of this study was to grade magnetic resonance white matter abnormalities (WMAs) of classical phenylketonuria (cPKU) patients treated from birth and to compare sensitivity and specificity of T2-weighted and diffusion-weighted images (DWI). Twenty early-treated cPKU patients still on a low-phenylalanine diet (12 males; mean age 21.2 years) and 26 normal subjects (ten males; mean age 25.1 years) were enrolled. Typical T2- and diffusion-weighted WMAs were semiquantitatively graded according to Thompson score (TS). Besides, a regional magnetic resonance imaging (MRI) score (mTS) was developed according to extension and intensity of WMAs. Phenylalanine and tyrosine plasma concentrations before performing MRI and the amino acid mean levels collected the year before MRI (Tyr{sub year} and Phe{sub year}) were measured. No patient with Phe{sub year} concentration below 460 {mu}mol/L showed WMAs. In cPKU patients, TS and mTS were significantly higher on DWI than on T2 images (3.50 vs 2.65 and 23.65 vs 15.85, respectively, p<0.002, Wilcoxon test). All controls were scored 0 on DWI, while in T2 images, TS and mTS were 0.19 and 1.70. DWI evaluated by mTS disclosed a frontotemporal, occipital, and parietal WM progressive involvement. TS and mTS, both on T2 images and on DWI, showed no correlation with tyrosine while they proved to have a strong correlation with phenylalaninemia and an excellent one with Phe{sub year} levels. Among the different MR sequences, DWI seems to be the most sensitive and reliable in detecting and grading the typical WMAs of cPKU patients. (orig.)

Phenylketonuria Scientific Review Conference: state of the science and future research needs.

Science.gov (United States)

Camp, Kathryn M; Parisi, Melissa A; Acosta, Phyllis B; Berry, Gerard T; Bilder, Deborah A; Blau, Nenad; Bodamer, Olaf A; Brosco, Jeffrey P; Brown, Christine S; Burlina, Alberto B; Burton, Barbara K; Chang, Christine S; Coates, Paul M; Cunningham, Amy C; Dobrowolski, Steven F; Ferguson, John H; Franklin, Thomas D; Frazier, Dianne M; Grange, Dorothy K; Greene, Carol L; Groft, Stephen C; Harding, Cary O; Howell, R Rodney; Huntington, Kathleen L; Hyatt-Knorr, Henrietta D; Jevaji, Indira P; Levy, Harvey L; Lichter-Konecki, Uta; Lindegren, Mary Lou; Lloyd-Puryear, Michele A; Matalon, Kimberlee; MacDonald, Anita; McPheeters, Melissa L; Mitchell, John J; Mofidi, Shideh; Moseley, Kathryn D; Mueller, Christine M; Mulberg, Andrew E; Nerurkar, Lata S; Ogata, Beth N; Pariser, Anne R; Prasad, Suyash; Pridjian, Gabriella; Rasmussen, Sonja A; Reddy, Uma M; Rohr, Frances J; Singh, Rani H; Sirrs, Sandra M; Stremer, Stephanie E; Tagle, Danilo A; Thompson, Susan M; Urv, Tiina K; Utz, Jeanine R; van Spronsen, Francjan; Vockley, Jerry; Waisbren, Susan E; Weglicki, Linda S; White, Desirée A; Whitley, Chester B; Wilfond, Benjamin S; Yannicelli, Steven; Young, Justin M

2014-06-01

New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use

Incidence of and risk factors for severe maternal complications associated with hypertensive disorders after 36 weeks' gestation in uncomplicated twin pregnancies: A prospective cohort study.

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Yamamoto, Ryo; Ishii, Keisuke; Muto, Haruka; Ota, Shiyo; Kawaguchi, Haruna; Hayashi, Shusaku; Mitsuda, Nobuaki

2018-04-19

To elucidate the incidence of and risk factors for severe hypertensive disorders (HD) and related maternal complications in uncomplicated twin pregnancies that reached 36 weeks' gestation. We conducted a prospective cohort study of twin pregnancies delivered after 36 weeks' gestation. Cases of twin-twin transfusion syndrome, twin anemia-polycythemia sequence, malformed fetuses, monoamniotic twins, selective reduction, fetal therapy and HD or fetal death before 35 weeks' gestation were excluded. The study's primary outcome was the incidence of severe maternal complications, including severe HD, eclampsia, placental abruption, HELLP (hemolysis, elevated liver enzyme and low platelet) syndrome, pulmonary edema and cerebrovascular disease. Perinatal factors associated with the primary outcome were identified using a multivariate logistic regression model. In 330 enrolled women, the number of cases with the primary outcome was 28 (8.5%; 95% confidence interval 5.9-12.0), including 25 cases of severe HD and each one case of placental abruption, HELLP syndrome and eclampsia. The rate of severe maternal complications significantly increased with gestational age, demonstrating 1.2% at 36 weeks, 3.9% at 37 weeks and 6.4% at 38 weeks. Only gestational proteinuria was identified as the independent risk factor for severe maternal complications (adjusted odds ratio 17.1 [95% confidence interval 6.71-45.4]). Severe maternal HD and related complications increased from late preterm to early term; particularly, patients with gestational proteinuria were at high risk. © 2018 Japan Society of Obstetrics and Gynecology.

Maternal factors predicting cognitive and behavioral characteristics of children with fetal alcohol spectrum disorders.

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May, Philip A; Tabachnick, Barbara G; Gossage, J Phillip; Kalberg, Wendy O; Marais, Anna-Susan; Robinson, Luther K; Manning, Melanie A; Blankenship, Jason; Buckley, David; Hoyme, H Eugene; Adnams, Colleen M

2013-06-01

To provide an analysis of multiple predictors of cognitive and behavioral traits for children with fetal alcohol spectrum disorders (FASDs). Multivariate correlation techniques were used with maternal and child data from epidemiologic studies in a community in South Africa. Data on 561 first-grade children with fetal alcohol syndrome (FAS), partial FAS (PFAS), and not FASD and their mothers were analyzed by grouping 19 maternal variables into categories (physical, demographic, childbearing, and drinking) and used in structural equation models (SEMs) to assess correlates of child intelligence (verbal and nonverbal) and behavior. A first SEM using only 7 maternal alcohol use variables to predict cognitive/behavioral traits was statistically significant (B = 3.10, p < .05) but explained only 17.3% of the variance. The second model incorporated multiple maternal variables and was statistically significant explaining 55.3% of the variance. Significantly correlated with low intelligence and problem behavior were demographic (B = 3.83, p < .05) (low maternal education, low socioeconomic status [SES], and rural residence) and maternal physical characteristics (B = 2.70, p < .05) (short stature, small head circumference, and low weight). Childbearing history and alcohol use composites were not statistically significant in the final complex model and were overpowered by SES and maternal physical traits. Although other analytic techniques have amply demonstrated the negative effects of maternal drinking on intelligence and behavior, this highly controlled analysis of multiple maternal influences reveals that maternal demographics and physical traits make a significant enabling or disabling contribution to child functioning in FASD.

Clinical abnormalities, early intervention program of Down syndrome children: Queen Sirikit National Institute of Child Health experience.

Science.gov (United States)

Fuengfoo, Adidsuda; Sakulnoom, Kim

2014-06-01

Queen Sirikit National Institute of Child Health is a tertiary institute of children in Thailand, where early intervention programs have been provided since 1990 by multidisciplinary approach especially in Down syndrome children. This aim of the present study is to follow the impact of early intervention on the outcome of Down syndrome children. The school attendance number of Down syndrome children was compared between regular early intervention and non-regular early intervention. The present study group consists of 210 Down syndrome children who attended early intervention programs at Queen Sirikit National Institute of Child Health between June 2008 and January 2012. Data include clinical features, school attendance developmental quotient (DQ) at 3 years of age using Capute Scales Cognitive Adaptive Test/Scale (CAT/CLAMS). Developmental milestones have been recorded as to the time of appearance of gross motor, fine motor, language, personal-social development compared to those non-regular intervention patients. Of 210 Down syndrome children, 117 were boys and 93 were girls. About 87% received regular intervention, 68% attended speech training. Mean DQ at 3 years of age was 65. Of the 184 children who still did follow-up at developmental department, 124 children (59%) attended school: mainstream school children 78 (63%) and special school children 46 (37%). The mean age at entrance to school was 5.8 ± 1.4 years. The school attendance was correlated with maternal education and regular early intervention attendance. Regular early intervention starts have proven to have a positive effect on development. The school attendance number of Down syndrome children receiving regular early intervention was statistically and significantly higher than the number of Down syndrome children receiving non-regular early intervention was. School attendance correlated with maternal education and attended regularly early intervention. Regular early intervention together with maternal

Frequency of maternal mortality and morbidity in pregnancy-induced hypertension

International Nuclear Information System (INIS)

Riaz, S.; Jabeen, A.

2011-01-01

Background: Pregnancy-induced hypertension (PIH) is defines as hypertension in pregnancy, and is sustained blood pressure >140 mm Hg systolic or 90 mm Hg diastolic. Objective of this study was to see the maternal outcome in terms of morbidity and mortality in PIH. Methods: This descriptive study was conducted in Obstetrics and Gynaecology Unit of Fauji Foundation Hospital, Rawalpindi from January to December 2010. Both booked and un-booked cases were selected after fulfilling inclusion criteria. A detailed history and clinical examination was recorded and relevant investigations were performed. Patients were monitored for rise in blood pressure, development of complications related to hypertensions in pregnancy as well as maternal and perinatal outcome. Results: During this period, 100 patients were admitted with pregnancy-induced hypertension. Majority were un-booked. Primigravida were 60 (60%), and were in age group 21-30 year, remaining were above 30 year. Four patients had placental abruption, 2 pulmonary oedema, 5 HELLP syndrome, 2 severe renal impairment, 20 elevated liver enzyme, 23 uncontrolled blood pressure, 20 server preeclampsia, 10 thrombocytopenia, 3 eclampsia, 10 had impaired coagulation profile, and 1 had maternal death. Conclusion: Pregnancy induced hypertension is a major cause of maternal mortality and morbidity. In Pakistan, its incidence and related mortality are high due to lack of adequate antenatal care. (author)

Physical and mental health of mothers caring for a child with Rett syndrome.

Science.gov (United States)

Laurvick, Crystal L; Msall, Michael E; Silburn, Sven; Bower, Carol; de Klerk, Nicholas; Leonard, Helen

2006-10-01

Our goal was to investigate the physical and mental health of mothers who care for a child with Rett syndrome. We assessed maternal physical and mental health by using the SF-12 version 1 physical component summary and mental component summary scores as the outcome measures of interest. Mothers (n = 135) of children with Rett syndrome completed the SF-12 measure as part of the Australian Rett Syndrome Study in 2002. The analysis investigated linear relationships between physical and mental health scores and maternal, family, and child characteristics. Mothers ranged in age from 21 to 60 years and their children from 3 to 27 years. Nearly half of these mothers (47.4%) indicated that they worked full-time or part-time outside the home, and 41% had a combined family (gross) income of health demonstrated that the following factors were positively associated with better maternal physical health: the mother working full-time or part-time outside the home, having some high school education, having private health insurance, the child not having breathing problems in the last 2 years, the child not having home-based structured therapy, and high scores on the Family Resource Scale (indicating adequacy of time resources for basic and family needs). The resultant model for mental health demonstrated that the following factors were positively associated with better maternal mental health: the mother working full-time or part-time outside the home, the child not having a fracture in the last 2 years, lesser reporting of facial stereotypes and involuntary facial movements, being in a well-adjusted marriage, and having low stress scores. Our study suggests that the most important predictors of maternal physical and emotional health are child behavior, caregiver demands, and family function.

Clinical spectrum of silver - Russell syndrome

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Sapna N.K. Varma

2013-01-01

Full Text Available Silver - Russell syndrome is a clinically and genetically heterogenous condition characterized by severe intrauterine and postnatal growth retardation, craniofacial disproportion and normal intelligence downward curvature of the corner of the mouth, syndactyly and webbed fingers. Diagnosis of Silver - Russell syndrome remains clinical; no definite etiology or specific tests have been established. In the recent years, it has been shown that more than 38% of patients have hypomethylation in the imprinting control region 1 of 11p15 and one-tenth of patients carry a maternal uniparental disomy of chromosome seven. The pathophysiological mechanisms resulting in the Silver - Russell phenotype remain unknown despite the recent progress in deciphering the molecular defects associated with this condition. This case report describes the clinical features of Silver - Russell syndrome in a father and daughter.

Obstetric antiphospholipid syndrome.

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Esteve-Valverde, E; Ferrer-Oliveras, R; Alijotas-Reig, J

2016-04-01

Obstetric antiphospholipid syndrome is an acquired autoimmune disorder that is associated with various obstetric complications and, in the absence of prior history of thrombosis, with the presence of antiphospholipid antibodies directed against other phospholipids, proteins called cofactors or PL-cofactor complexes. Although the obstetric complications have been related to the procoagulant properties of antiphospholipid antibodies, pathological studies of human placenta have shown the proinflammatory capacity of antiphospholipid antibodies via the complement system and proinflammatory cytokines. There is no general agreement on which antiphospholipid antibodies profile (laboratory) confers the greatest obstetric risk, but the best candidates are categories I and IIa. Combined treatment with low doses of aspirin and heparin achieves good obstetric and maternal outcomes. In this study, we also review the therapeutic possibilities in refractory cases, although the likelihood of progressing to other autoimmune diseases is low. We briefly comment on incomplete obstetric antiphospholipid syndrome, also known as antiphospholipid antibody-mediated pregnancy morbidity syndrome. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Phenylketonuria and Hirschsprung Disease—A Report of an Unusual Neonatal Presentation

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Nina Lenherr

2017-08-01

Full Text Available We describe a term born boy of non-consanguineous Swiss parents with tetrahydrobiopterine (BH4-responsive Phenylketonuria (PKU and Hirschsprung disease with unusual neonatal presentation. The child presented with floppiness, irritability, recurrent bilious vomiting and failure to pass meconium until 32 hours after birth, resulting in the clinical suspicion of an intoxication-type metabolic disease such as maple syrup urine disease (MSUD. Although the slightly elevated branched-chain amino acids in newborn screening on the fourth day of life initially supported the clinical suspicion of MSUD, the elevated Phenylalanine (Phe of 650 µmol/L, low Tyrosine (Tyr of 30 µmol/L, and a Phe/Tyr ratio of 22, led to the diagnosis of PKU. BH4-testing resulted in a significant decrease of Phe from 1011 to 437 µmol/L within 24 h. Urinary pterins and dihydropteridine reductase (DHPR activity were normal, supporting the diagnosis of BH4-responsive PKU. Dietary restriction of Phe was initiated immediately, but oral feeding turned out to be difficult because of gastrointestinal symptoms. Intestinal motility disorder was suspected due to distended abdomen, obstructive symptoms and radiological findings with dilated intestinal loops and lack of intestinal gas in the anorectal region. Hirschsprung disease was confirmed by rectal suction biopsies and treated by a laparoscopically-assisted transanal pull-through (de la Torre procedure. The boy is additionally compound heterozygous for two mutations in the phenylalanine hydroxylase (PAH gene, which confirmed BH4-responsive PKU. It is the first case to be described in the literature of the comorbidity of PKU and Hirschsprung disease.

Maternal Metabolic Syndrome Programs Mitochondrial Dysfunction via Germline Changes across Three Generations

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Jessica L. Saben

2016-06-01

Full Text Available Maternal obesity impairs offspring health, but the responsible mechanisms are not fully established. To address this question, we fed female mice a high-fat/high-sugar diet from before conception until weaning and then followed the outcomes in the next three generations of offspring, all fed a control diet. We observed that female offspring born to obese mothers had impaired peripheral insulin signaling that was associated with mitochondrial dysfunction and altered mitochondrial dynamic and complex proteins in skeletal muscle. This mitochondrial phenotype persisted through the female germline and was passed down to the second and third generations. Our results indicate that maternal programming of metabolic disease can be passed through the female germline and that the transfer of aberrant oocyte mitochondria to subsequent generations may contribute to the increased risk for developing insulin resistance.

Cushing's syndrome in pregnancy and neonatal hypertrophic obstructive cardiomyopathy.

Science.gov (United States)

Fayol, L; Masson, P; Millet, V; Simeoni, U

2004-10-01

Cushing's syndrome is rare in pregnancy but can cause spontaneous abortion, stillbirth or premature birth. We report a case of transient hypertrophic obstructive cardiomyopathy in a newborn whose mother had hypercortisolism due to a primary adrenal lesion. There was no family history of hypertrophic obstructive cardiomyopathy. Follow-up revealed complete resolution of the cardiac abnormalities in the infant. Cushing's syndrome in the mother resolved after delivery. Although maternal hypercortisolism seldom results in symptomatic hypercortisolism in the newborn, hypertrophic obstructive cardiomyopathy can occur.

Down's syndrome in South Africa - incidence, maternal age and ...

African Journals Online (AJOL)

Down's syndrome (DS) is the most common chromosomal cause of mental retardation, and amniocentesis is the most significant factor affecting its prevalence. In South Africa, prenatal cytogenetic diagnoses have been available for just over a decade and the utilisation and effect of this procedure in the white population ...

Long-term treatment of phenylketonuria with a new medical food containing large neutral amino acids.

Science.gov (United States)

Concolino, D; Mascaro, I; Moricca, M T; Bonapace, G; Matalon, K; Trapasso, J; Radhakrishnan, G; Ferrara, C; Matalon, R; Strisciuglio, P

2017-01-01

Phenylketonuria (PKU) is an autosomal recessive disease caused by deficient activity of phenylalanine hydroxylase. A low phenylalanine (Phe) diet is used to treat PKU. The diet is very restrictive, and dietary adherence tends to decrease as patients get older. Methods to improve dietary adherence and blood Phe control are continuously under investigation. A new formula Phe-neutral amino acid (PheLNAA) has been tested in this study with the purpose of improving the compliance and lowering blood phenylalanine. The formula has been tested for nitrogen balance, and it is nutritionally complete. It is fortified with more nutritional additives that can be deficient in the PKU diet, such as B12, Biotin, DHA, Lutein and increased levels of large neutral amino acids to help lower blood Phe. The new formula has been tested on 12 patients with a loading test of 4 weeks. Fifty-eight percent of patients had a significant decline in blood Phe concentration from baseline throughout the study. The PheLNAA was well tolerated with excellent compliance and without illnesses during the study. In conclusion, the new formula is suitable for life-long treatment of PKU, and it offers the PKU clinic a new choice for treatment.

Co-existence of Phenylketonuria and Fabry disease on a 3 year-old boy: case report

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Bonapace Giuseppe

2010-05-01

Full Text Available Abstract Background The co-existence of two genetically distinct metabolic disorders in the same patient has rarely been reported. Phenylketonuria (PKU is an inborn error of the metabolism resulting from a phenylalanine hydroxylase deficiency. Fabry disease (FD is an X-linked lysosomal storage disorder due to a deficiency of the enzyme alpha-galactosidase A. Case presentation We report a case of a 3 year- old boy affected by classic PKU and FD, both confirmed by molecular data. The FD was suspected at the age of 21 months on the presence of non-specific GI symptoms (severe abdominal pain and periodically appearance of not specific episodes of gastroenteritis apparently non related to PKU. Conclusion This is the first report of co-existence of FD and PKU, two different congenital inborn of metabolism and in consideration of the prevalence of each disease this chance association is a very unusual event. The co-existence of this diseases made very difficult the correct interpretation of clinical symptoms as lack of appetite, severe abdominal pain and non-specific gastroenteritis episodes. Furthermore, this case report helps to define the early clinical phenotype of FD.

Renal involvement in MELAS syndrome - a series of 5 cases and review of the literature.

Science.gov (United States)

Seidowsky, Alexandre; Hoffmann, Maxime; Glowacki, François; Dhaenens, Claire-Marie; Devaux, Jean-Philippe; de Sainte Foy, Celia Lessore; Provot, François; Gheerbrant, Jean-Dominique; Hummel, Aurelie; Hazzan, Marc; Dracon, Michel; Dieux-Coeslier, Anne; Copin, Marie-Christine; Noël, Christian; Buob, David

2013-12-01

Renal dysfunction is increasingly recognized as a potential clinical feature of mitochondrial cytopathies such as mitochondrial encephalomyopathy, lacticacidosis and stroke-like episodes (MELAS) syndrome. Five cases of MELAS syndrome with renal involvement from 4 unrelated families are presented in this case series. Three of the 5 patients had a history of maternally-inherited diabetes and/or deafness. Focal and segmental glomerulosclerosis and arteriolar hyaline thickening were the most striking findings on renal biopsy. In addition to clinical presentation with the typical symptoms of MELAS syndrome, genetic testing in these patients identified the A3243G point mutation in the tRNALeu gene of the mitochondrial DNA (mtDNA). The diagnosis of MELAS syndrome was thus considered to be unequivocal. The incidence of kidney disease in MELAS syndrome may be underestimated although a study is required to investigate this hypothesis. As the A3243G mtDNA mutation leads to a progressive adult-onset form of focal segmental glomerulosclerosis (FSGS), screening for the MELAS A3243G mtDNA mutation should therefore be performed especially in patients with maternally-inherited diabetes or hearing loss presenting with FSGS.

Serum Lycopene Concentrations and Associations with Clinical Outcomes in a Cohort of Maternal-Infant Dyads

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Corrine Hanson

2018-02-01

Full Text Available Oxidative stress has been associated with adverse neonatal outcomes, and many carotenoids, including lycopene, potentially have antioxidant properties. The objective of this analysis was to explore the associations between serum lycopene concentrations, including lycopene isomers, and maternal-newborn outcomes. Maternal and cord blood samples were collected in 180 mother-infant pairs. Serum of total lycopene as well as the cis- and trans-isomers concentrations were measured using HPLC (High Performance Liquid Chromatography. Descriptive statistics were calculated; Spearman coefficients were used to assess correlations between maternal and cord concentrations. The relationship between lycopene concentration and outcomes were evaluated with linear and logistic regression models, with adjustment for relevant confounders. A p ≤ 0.05 was considered statistically significant. Maternal and cord serum lycopene concentrations were positively correlated for total lycopene (r = 0.30, p < 0.0001, cis-lycopene (r = 0.29, p = 0.0002; and trans-lycopene (r = 0.32, p < 0.0001. Maternal concentrations of cis-lycopene were significantly lower in mothers whose infants developed respiratory distress syndrome compared to those who did not (0.336 ± 0.171 vs. 0.445 ± 0.238 µmol/L, p = 0.04 and also in mothers whose babies were admitted to the newborn intensive care unit compared to those who were not (0.380 ± 0.202 vs. 0.458 ± 0.244 µmol/L, p = 0.04. Conversely, cord concentrations of trans-lycopene were significantly higher in infants who developed RDS (Respiratory Distress Syndrome (0.023 ± 0.012 vs. 0.016 ± 0.012, p = 0.007 for RDS vs. no RDS, and a similar pattern was seen NICU admission (0.023 ± 0.016 vs. 0.015 ± 0.009 µmol/L for NICU (Newborn Intensive Care Unit admission vs. no NICU admission, p = 0.007. Maternal concentrations of total and cis-lycopene were positively associated with infant birth weight, length and head circumference after

Situational analysis of dietary challenges of the treatment regimen for children and adolescents with phenylketonuria and their primary caregivers.

Science.gov (United States)

Ievers-Landis, Carolyn E; Hoff, Ahna L; Brez, Caitlin; Cancilliere, Mary Kathryn; McConnell, Judy; Kerr, Douglas

2005-06-01

A situational analysis was conducted to evaluate challenges with the treatment regimen (a low protein diet and special supplemental formula) for children and adolescents with phenylketonuria (PKU) and their caregivers. A semistructured interview was administered to 19 caregivers and 11 children with PKU to describe formula and dietary problems and their frequency, difficulty, and affective intensity. Information was also gathered on attempted solutions to problems and their perceived effectiveness. Caregivers who rated dietary problems as less frequent, difficult, and emotionally upsetting and strategies as more effective for solving problems had children with significantly lower phenylalanine (Phe) levels, a biological indicator of adherence (i.e., better adherence; all p values authoritarian parenting style to solve dietary problems were significantly more likely to have lower household incomes and older children with higher Phe levels than were those who did not report such strategies (all p values <.05).

Pharmacologic inhibition of L-tyrosine degradation ameliorates cerebral dopamine deficiency in murine phenylketonuria (PKU)

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Harding, Cary O.; Winn, Shelley R.; Gibson, K. Michael; Arning, Erland; Bottiglieri, Teodoro; Grompe, Markus

2014-01-01

Summary Monoamine neurotransmitter deficiency has been implicated in the etiology of neuropsychiatric symptoms associated with chronic hyperphenylalaninemia in phenylketonuria (PKU). Two proposed explanations for neurotransmitter deficiency in PKU include first, that chronically elevated blood L-phenylalanine (Phe) inhibits the transport of L-tyrosine (Tyr) and L-tryptophan (Trp), the substrates for dopamine and serotonin synthesis respectively, into brain. In the second hypothesis, elevated Phe competitively inhibits brain tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) activities, the rate limiting steps in dopamine and serotonin synthesis. Dietary supplementation with large neutral amino acids (LNAA) including Tyr and Trp has been recommended for individuals with chronically elevated blood Phe in an attempt to restore amino acid and monoamine homeostasis in brain. As a potential alternative treatment approach, we demonstrate that pharmacologic inhibition of Tyr degradation through oral administration of nitisinone (NTBC) yielded sustained increases in blood and brain Tyr, decreased blood and brain Phe, and consequently increased dopamine synthesis in a murine model of PKU. Our results suggest that Phe-mediated inhibition of TH activity is the likely mechanism of impaired dopamine synthesis in PKU. Pharmacologic inhibition of Tyr degradation may be a promising adjunct therapy for CNS monoamine neurotransmitter deficiency in hyperphenylalaninemic individuals with PKU. PMID:24487571

Successful Pregnancy Outcome In Maternal Crigler Najjar Syndrome Type II

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Shakuntala PN

2012-10-01

Full Text Available Estimated incidence of Crigler-Najjar syndrome(CNS is 1 case per 1,000,000 births(1 million. The overall prevalence of CN syndrome is unknown, with only several hundred people reported to have this disease. It is interestingly very rare to encounter a pregnant adult women with congenital jaundice. Pregnancy in CN type II patients is a diagnostic and a therapeutic challenge because of the high risk of bilirubin encephalopathy with serious neurological damage as life-threatening complications for the fetus. To date 8 pregnancy outcome have been reported from 5 women and we report the6 woman with a successful 9 th pregnancy outcome. We have discussed detail history, presentation and management during pregnancy and care of the new born.

Metabolomics of Dietary Fatty Acid Restriction in Patients with Phenylketonuria

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Mütze, Ulrike; Beblo, Skadi; Kortz, Linda; Matthies, Claudia; Koletzko, Berthold; Bruegel, Mathias; Rohde, Carmen; Thiery, Joachim; Kiess, Wieland; Ceglarek, Uta

2012-01-01

Background Patients with phenylketonuria (PKU) have to follow a lifelong phenylalanine restricted diet. This type of diet markedly reduces the intake of saturated and unsaturated fatty acids especially long chain polyunsaturated fatty acids (LC-PUFA). Long-chain saturated fatty acids are substrates of mitochondrial fatty acid oxidation for acetyl-CoA production. LC-PUFA are discussed to affect inflammatory and haemostaseological processes in health and disease. The influence of the long term PKU diet on fatty acid metabolism with a special focus on platelet eicosanoid metabolism has been investigated in the study presented here. Methodology/Principal Findings 12 children with PKU under good metabolic control and 8 healthy controls were included. Activated fatty acids (acylcarnitines C6–C18) in dried blood and the cholesterol metabolism in serum were analyzed by liquid chromatographic tandem mass spectrometry (LC-MS/MS). Fatty acid composition of plasma glycerophospholipids was determined by gas chromatography. LC-PUFA metabolites were analyzed in supernatants by LC-MS/MS before and after platelet activation and aggregation using a standardized protocol. Patients with PKU had significantly lower free carnitine and lower activated fatty acids in dried blood compared to controls. Phytosterols as marker of cholesterol (re-) absorption were not influenced by the dietary fatty acid restriction. Fatty acid composition in glycerophospholipids was comparable to that of healthy controls. However, patients with PKU showed significantly increased concentrations of y-linolenic acid (C18:3n-6) a precursor of arachidonic acid. In the PKU patients significantly higher platelet counts were observed. After activation with collagen platelet aggregation and thromboxane B2 and thromboxane B3 release did not differ from that of healthy controls. Conclusion/Significance Long-term dietary fatty acid restriction influenced the intermediates of mitochondrial beta-oxidation. No functional

Metabolomics of dietary fatty acid restriction in patients with phenylketonuria.

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Ulrike Mütze

Full Text Available BACKGROUND: Patients with phenylketonuria (PKU have to follow a lifelong phenylalanine restricted diet. This type of diet markedly reduces the intake of saturated and unsaturated fatty acids especially long chain polyunsaturated fatty acids (LC-PUFA. Long-chain saturated fatty acids are substrates of mitochondrial fatty acid oxidation for acetyl-CoA production. LC-PUFA are discussed to affect inflammatory and haemostaseological processes in health and disease. The influence of the long term PKU diet on fatty acid metabolism with a special focus on platelet eicosanoid metabolism has been investigated in the study presented here. METHODOLOGY/PRINCIPAL FINDINGS: 12 children with PKU under good metabolic control and 8 healthy controls were included. Activated fatty acids (acylcarnitines C6-C18 in dried blood and the cholesterol metabolism in serum were analyzed by liquid chromatographic tandem mass spectrometry (LC-MS/MS. Fatty acid composition of plasma glycerophospholipids was determined by gas chromatography. LC-PUFA metabolites were analyzed in supernatants by LC-MS/MS before and after platelet activation and aggregation using a standardized protocol. Patients with PKU had significantly lower free carnitine and lower activated fatty acids in dried blood compared to controls. Phytosterols as marker of cholesterol (re- absorption were not influenced by the dietary fatty acid restriction. Fatty acid composition in glycerophospholipids was comparable to that of healthy controls. However, patients with PKU showed significantly increased concentrations of y-linolenic acid (C18:3n-6 a precursor of arachidonic acid. In the PKU patients significantly higher platelet counts were observed. After activation with collagen platelet aggregation and thromboxane B(2 and thromboxane B(3 release did not differ from that of healthy controls. CONCLUSION/SIGNIFICANCE: Long-term dietary fatty acid restriction influenced the intermediates of mitochondrial beta

Genetic and clinical characteristics of patients with phenylketonuria in Slovenia

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Urh Grošelj

2013-12-01

Full Text Available Phenylketonuria (PKU, an autosomal recessive disease, is the most common inborn error of amino acid metabolism in Caucasians, affecting 1/10,000 individuals. PKU is caused by the deficiency of hepatic phenylalanine hydroxylase (PAH, which catalyzes the hydroxylation of phenylalanine (Phe to tyrosine, using tetrahydrobiopterin (BH4 as a cofactor. The PAH gene is located on the chromosome 12 and consists of 13 exons. Over 600 different mutations of the PAH gene have been identified to date, which result in a broad spectrum of PAH deficiency. The resulting elevation of Phe in the blood (hyperphenilalaninemia – HPA could cause mental retardation if left untreated. The classification of PKU is based on the metabolic phenotype of a patient (according to HPA level; discerned could be three subclasses of PKU (classic, moderate, mild and mild HPA, which is a separate clinical entity.The incidence of classical PKU in the Slovene population was estimated to be 1/10,000, corresponding to a carrier frequency of about 1/50. The cumulative incidence of all subtypes of PKU (classic, moderate, mild is around 1/6,000; the incidence of mild HPA is around 1/3,500. The article also reviews the previously published studies on the genetic and phenotypic characteristics of Slovenian PKU patients, performed at the Department of Pediatric Endocrinology, Diabetes and Metabolism, University Children’s Hospital Ljubljana, in years 2008–2012. The genetic characteristics of the Slovenian PKU population were concordant with other neighbouring populations; five novel mutations of PAH gene were detected in the population.The mandatory neonatal PKU screening in Slovenia was implemented in 1979. The dietary therapy based on a restricted Phe intake should be introduced as soon as possible after birth; in responders, BH4 treatment increases the dietary Phe tolerance.

Feto portador de síndrome de turner e tetralogia de fallot associadas à elevação de alfafetoproteína materna Fetal turner syndrome and tetralogy of fallot associated with elevated maternal serum alpha-fetoprotein levels

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Eduardo Vieira Neto

1998-06-01

Full Text Available A síndrome de Turner fetal e suas complicações, a hidropisia e o higroma cístico, podem produzir alteração dos marcadores bioquímicos de soro materno inicialmente utilizados no rastreamento de síndrome de Down e de defeitos de tubo neural (DTN. Os autores relatam o caso de uma gestante de 37 anos, que foi rastreada para síndrome de Down e DTN no início do 2º trimestre. Foi constatado aumento da alfafetoproteína de soro materno (MSAFP e o rastreamento foi considerado positivo para DTN. Foi realizado exame ultra-sonográfico tridimensional, que não demonstrou nenhuma anormalidade fetal ou placentária, caracterizando o caso como elevação idiopática de MSAFP. No 3º trimestre, a gravidez evoluiu com acentuada oligoidrâmnia e alteração do fluxo uteroplacentário, obrigando à instituição de terapia com corticosteróides e parto cesáreo na 34ª semana gestacional. O concepto do sexo feminino foi encaminhado à UTI neonatal, onde foram diagnosticadas tetralogia de Fallot e síndrome de Turner. Esse caso incentivou os autores a rever a literatura sobre marcadores bioquímicos de soro materno na síndrome de Turner e nas malformações cardíacas congênitas. Ao final, propõe-se um protocolo para elevação idiopática de MSAFP.Turner syndrome and its complications, hydrops and cystic hygroma, can produce alterations in maternal serum biochemical markers used in screening for Down's syndrome and neural tube defects (NTD. The authors report the case of a 37-year-old pregnant woman, screened for Down's syndrome and NTD in the second trimester of pregnancy. The maternal serum alpha-fetoprotein (MSAFP level was increased and the test was considered screen positive for NTD. A three-dimensional ultrasound investigation was performed, but no fetal or placental anomalies were found, indicating a case of unexplained increased msafp. In the third trimester severe oligohydramnios and disturbances in uteroplacental arterial circulation

Severe acute maternal morbidity and maternal death audit - a rapid ...

African Journals Online (AJOL)

Severe acute maternal morbidity and maternal death audit - a rapid diagnostic tool for evaluating maternal care. L Cochet, R.C. Pattinson, A.P. Macdonald. Abstract. Objective. To analyse severe acute maternal morbidity (SAMM) and maternal mortality in the Pretoria region over a 2-year period (2000 - 2001). Setting.

Cross-trimester repeated measures testing for Down's syndrome screening: an assessment.

LENUS (Irish Health Repository)

Wright, D

2010-07-01

To provide estimates and confidence intervals for the performance (detection and false-positive rates) of screening for Down\\'s syndrome using repeated measures of biochemical markers from first and second trimester maternal serum samples taken from the same woman.

Nutritional status of patients with phenylketonuria in Japan

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Yoshiyuki Okano

2016-09-01

Full Text Available Accumulating evidence suggests that hyperphenylalaninemia in phenylketonuria (PKU can cause neuropsychological and psychosocial problems in diet-off adult patients, and that such symptoms improve after resumption of phenylalanine-restricted diet, indicating the need for lifetime low-phenylalanine diet. While limiting protein intake, dietary therapy should provide adequate daily intake of energy, carbohydrates, fat, vitamins, and microelements. We evaluated nutrient balance in 14 patients with classical PKU aged 4–38 years. Approximately 80–85% of the recommended dietary allowance (RDA of protein in Japanese was supplied through phenylalanine-free (Phe-free milk and Phe-free amino acid substitutes. Nutritional evaluation showed that the calorie and protein intakes were equivalent to the RDA. Phenylalanine intake was 9.8 ± 2.2 mg/kg of body weight/day, which maintained normal blood phenylalanine concentration by the 80% Phe-free protein rule. The protein, fat, and carbohydrate ratio was 9.5:23.9:66.6% with relative carbohydrate excess. Phe-free milk and amino acid substitutes provided 33.7% of carbohydrate, 82.1% of protein, and 66.7% of fat intake in all. Selenium and biotin intakes were 25.0% and 18.1% of the RDA and adequate intake (AI for Japanese, respectively; both were not included in Phe-free milk. PKU patients showed low serum selenium, low urinary biotin, and high urinary 3-hydroxyisovaleric acid in this study. The intakes of magnesium, zinc, and iodine were low (71.5%, 79.5%, and 71.0% of the RDA, respectively and that of phosphorus was 79.7% of the AI, although they were supplemented in Phe-free milk. PKU patients depend on Phe-free milk and substitutes for daily requirement of microelements and vitamins as well as protein and fat. Development of low-protein food makes it possible to achieve the aimed phenylalanine blood level, but this lowers the intake of microelements and vitamins from natural foods. The dietary habits vary

Maternal and perinatal outcomes of dengue in PortSudan, Eastern Sudan

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Elbashir Hagir M

2010-07-01

Full Text Available Abstract Aim To investigate maternal and perinatal outcomes (maternal death, preterm delivery, low birth weight and perinatal mortality of dengue at PortSudan and Elmawani hospitals in the eastern Sudan. Method This was a retrospective Cohort study where medical files of women with dengue were reviewed. Results There were 10820 deliveries and 78 (0.7% pregnant women with confirmed dengue IgM serology at the mean (SD gestational age of 29.4(8.2 weeks. While the majority of these women had dengue fever (46, 58.9%, hemorrhagic fever and dengue shock syndrome were the presentations in 18 (23.0% and 12, (15.3% of these women, respectively. There were 17(21.7% maternal deaths. Fourteen (17.9% of these 78 women had preterm deliveries and 19 (24.3% neonates were admitted to neonatal intensive care unit. Nineteen (24.3% women gave birth to low birth weight babies. There were seven (8.9% perinatal deaths. Eight (10.2% patients delivered by caesarean section due to various obstetrical indications. Conclusion Thus dengue has poor maternal and perinatal outcomes in this setting. Preventive measures against dengue should be employed in the region, and more research on dengue during pregnancy is needed.

Dietary intervention in the management of phenylketonuria: current perspectives

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Rocha JC

2016-12-01

Full Text Available Júlio César Rocha,1-3 Anita MacDonald4 1Centro de Genética Médica, Centro Hospitalar do Porto – CHP, 2Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, 3Center for Health Technology and Services Research (CINTESIS, Porto, Portugal; 4The Children’s Hospital, Birmingham, UK Abstract: Phenylketonuria (PKU is a well-described inborn error of amino acid metabolism that has been treated for >60 years. Enzyme deficiency causes accumulation of phenylalanine (Phe and if left untreated will lead to profound and irreversible intellectual disability in most children. Traditionally, it has been managed with a low-Phe diet supplemented with a Phe-free protein substitute although newer treatment options mainly in combination with diet are available for some subgroups of patients with PKU, for example, sapropterin, large neutral amino acids, and glycomacropeptide. The diet consists of three parts: 1 severe restriction of dietary Phe; 2 replacement of non-Phe L-amino acids with a protein substitute commonly supplemented with essential fatty acids and other micronutrients; and 3 low-protein foods from fruits, some vegetables, sugars, fats and oil, and special low-protein foods (SLPF. The prescription of diet is challenging for health professionals. The high-carbohydrate diet supplied by a limited range of foods may program food preferences and contribute to obesity in later life. Abnormal tasting and satiety-promoting protein substitutes are administered to coincide with peak appetite times to ensure their consumption, but this practice may impede appetite for other important foods. Intermittent dosing of micronutrients when combined with L-amino acid supplements may lead to their poor bioavailability. Much work is required on the ideal nutritional profiling for special SLPF and Phe-free L-amino acid supplements. Although non-diet treatments are being studied, it is important to continue to fully understand all the consequences of diet

Maternal pre-pregnancy obesity and neuropsychological development in pre-school children: a prospective cohort study.

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Casas, Maribel; Forns, Joan; Martínez, David; Guxens, Mònica; Fernandez-Somoano, Ana; Ibarluzea, Jesus; Lertxundi, Nerea; Murcia, Mario; Rebagliato, Marisa; Tardon, Adonina; Sunyer, Jordi; Vrijheid, Martine

2017-10-01

BackgroundMaternal pre-pregnancy obesity may impair infant neuropsychological development, but it is unclear whether intrauterine or confounding factors drive this association.MethodsWe assessed whether maternal pre-pregnancy obesity was associated with neuropsychological development in 1,827 Spanish children. At 5 years, cognitive and psychomotor development was assessed using McCarthy Scales of Children's Abilities, attention deficit hyperactivity disorder (ADHD) symptoms using the Criteria of Diagnostic and Statistical Manual of Mental Disorders, and autism spectrum disorder symptoms using the Childhood Asperger Syndrome Test. Models were adjusted for sociodemographic factors and maternal intelligence quotient. We used paternal obesity as negative control exposure as it involves the same source of confounding than maternal obesity.ResultsThe percentage of obese mothers and fathers was 8% and 12%, respectively. In unadjusted models, children of obese mothers had lower scores than children of normal weight mothers in all McCarthy subscales. After adjustment, only the verbal subscale remained statistically significantly reduced (β: -2.8; 95% confidence interval: -5.3, -0.2). No associations were observed among obese fathers. Maternal and paternal obesity were associated with an increase in ADHD-related symptoms. Parental obesity was not associated with autism symptoms.ConclusionMaternal pre-pregnancy obesity was associated with a reduction in offspring verbal scores at pre-school age.

Inactivation of the maternal fragile X gene results in sensitization of GABAB receptor function in the offspring

OpenAIRE

Zupan, Bojana; Toth, Miklos

2008-01-01

Fragile X syndrome is an X linked disorder caused by the inactivation of the FMR-1 gene with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities and hyperactivity. Although Fragile X syndrome is considered a typical Mendelian disorder, we have recently reported that the environment, specifically the fmr-1+/− or fmr-1−/− (H or KO) maternal environment, elicits on its own a partial fragile X-like phenotype and can contribute to the overall phenotype of...

BDNF expression in the hippocampus of maternally separated rats: does Bifidobacterium breve 6330 alter BDNF levels?

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O'Sullivan, E; Barrett, E; Grenham, S; Fitzgerald, P; Stanton, C; Ross, R P; Quigley, E M M; Cryan, J F; Dinan, T G

2011-09-01

Brain-derived neurotrophic factor (BDNF) is of interest because of its putative role in stress and psychiatric disorders. Maternal separation is used as an animal model of early-life stress and of irritable bowel syndrome (IBS). Animals exposed to the paradigm show altered gut function together with heightened levels of arousal and corticosterone. Some probiotic organisms have been shown to be of benefit in IBS and influence the brain-gut axis. Our objective was to investigate the effects of maternal separation on BDNF under basal conditions and in response to the probiotic Bifidobacterium breve 6330. The study implemented the maternal separation model which we have previously described. Polymerase chain reaction and in situ hybridisation were performed to measure the effect of maternal separation on both BDNF total variants and BDNF splice variant (exon) IV in the hippocampus. Maternally separated and non-separated rats were treated with B. breve 6330, to investigate the effect of this probiotic on BDNF total variant and BDNF exon IV expression. Maternal separation increased BDNF total variants (Pbreve 6330 increased BDNF total variants (Pbreve 6330 did not alter BDNF levels in the maternally separated rats. Maternal separation caused a marked increase in BDNF in the hippocampus. While B. breve 6330 influenced BDNF in normal animals, it had no significant effect on BDNF in those which were maternally separated. We have demonstrated that an orally administered probiotic can influence hippocampal BDNF.

Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring.

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Manti, Maria; Fornes, Romina; Qi, Xiaojuan; Folmerz, Elin; Lindén Hirschberg, Angelica; de Castro Barbosa, Thais; Maliqueo, Manuel; Benrick, Anna; Stener-Victorin, Elisabet

2018-03-22

Maternal polycystic ovary syndrome (PCOS), a condition associated with hyperandrogenism, is suggested to increase anxiety-like behavior in the offspring. Because PCOS is closely linked to obesity, we investigated the impact of an adverse hormonal or metabolic maternal environment and offspring obesity on anxiety in the offspring. The obese PCOS phenotype was induced by chronic high-fat-high-sucrose (HFHS) consumption together with prenatal dihydrotestosterone exposure in mouse dams. Anxiety-like behavior was assessed in adult offspring with the elevated-plus maze and open-field tests. The influence of maternal androgens and maternal and offspring diet on genes implicated in anxiety were analyzed in the amygdala and hypothalamus with real-time PCR ( n = 47). Independent of diet, female offspring exposed to maternal androgens were more anxious and displayed up-regulation of adrenoceptor α 1B in the amygdala and up-regulation of hypothalamic corticotropin-releasing hormone ( Crh). By contrast, male offspring exposed to a HFHS maternal diet had increased anxiety-like behavior and showed up-regulation of epigenetic markers in the amygdala and up-regulation of hypothalamic Crh. Overall, there were substantial sex differences in gene expression in the brain. These findings provide novel insight into how maternal androgens and obesity exert sex-specific effects on behavior and gene expression in the offspring of a PCOS mouse model.-Manti, M., Fornes, R., Qi, X., Folmerz, E., Lindén Hirschberg, A., de Castro Barbosa, T., Maliqueo, M., Benrick, A., Stener-Victorin, E. Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring.

Prenatal diagnosis of Caudal Regression Syndrome : a case report

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Celikaslan Nurgul

2001-12-01

Full Text Available Abstract Background Caudal regression is a rare syndrome which has a spectrum of congenital malformations ranging from simple anal atresia to absence of sacral, lumbar and possibly lower thoracic vertebrae, to the most severe form which is known as sirenomelia. Maternal diabetes, genetic predisposition and vascular hypoperfusion have been suggested as possible causative factors. Case presentation We report a case of caudal regression syndrome diagnosed in utero at 22 weeks' of gestation. Prenatal ultrasound examination revealed a sudden interruption of the spine and "frog-like" position of lower limbs. Termination of pregnancy and autopsy findings confirmed the diagnosis. Conclusion Prenatal ultrasonographic diagnosis of caudal regression syndrome is possible at 22 weeks' of gestation by ultrasound examination.

Prader-Willi Syndrome and Schaaf-Yang Syndrome: Neurodevelopmental Diseases Intersecting at the MAGEL2 Gene

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Michael D. Fountain

2016-01-01

Full Text Available Prader-Willi syndrome (PWS is a neurodevelopmental disorder characterized by neonatal hypotonia, developmental delay/intellectual disability, and characteristic feeding behaviors with failure to thrive during infancy; followed by hyperphagia and excessive weight gain later in childhood. Individuals with PWS also manifest complex behavioral phenotypes. Approximately 25% meet criteria for autism spectrum disorder (ASD. PWS is caused by the absence of paternally expressed, maternally silenced genes at chromosome 15q11-q13. MAGEL2 is one of five protein-coding genes in the PWS-critical domain. Truncating point mutations of the paternal allele of MAGEL2 cause Schaaf-Yang syndrome, which has significant phenotypic overlap with PWS, but is also clinically distinct; based on the presence of joint contractures, and a particularly high prevalence of autism spectrum disorder (up to 75% of affected individuals. The clinical and molecular overlap between PWS and Schaaf-Yang syndrome, but also their distinguishing features provide insight into the pathogenetic mechanisms underlying both disorders.

Modeling Family Dynamics in Children with Fragile X Syndrome

Science.gov (United States)

Hall, Scott S.; Burns, David D.; Reiss, Allan L.

2007-01-01

Few studies have examined the impact of children with genetic disorders and their unaffected siblings on family functioning. In this study, the reciprocal causal links between problem behaviors and maternal distress were investigated in 150 families containing a child with fragile X syndrome (FXS) and an unaffected sibling. Both children's…

Congenital heart disease linked to maternal autoimmunity against cardiac myosin.

Science.gov (United States)

Cole, Charles R; Yutzey, Katherine E; Brar, Anoop K; Goessling, Lisa S; Van Vickle-Chavez, Sarah J; Cunningham, Madeleine W; Eghtesady, Pirooz

2014-05-01

Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-β-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.

Brief Psychotherapy for Maternal Depression: Impact on Mothers and Children.

Science.gov (United States)

Swartz, Holly A; Cyranowski, Jill M; Cheng, Yu; Zuckoff, Allan; Brent, David A; Markowitz, John C; Martin, Stacy; Amole, Marlissa C; Ritchey, Fiona; Frank, Ellen

2016-06-01

Two-generation studies demonstrate that treating maternal depression benefits school-age children. Although mothers prefer psychotherapy to medication, little is known about how psychotherapy for maternal depression affects offspring, especially in very high-risk families in which both mothers and children concurrently meet syndromal criteria for psychiatric disorders. This trial evaluated the effects of 2 brief psychotherapies for maternal depression on very high-risk families. Mothers with major depressive disorder were randomly assigned to 9 sessions of either brief interpersonal psychotherapy for mothers (IPT-MOMS; n = 85) or brief supportive psychotherapy (BSP; n = 83). Independent assessors evaluated mothers and their children, ages 7 to 18 years, diagnosed with at least 1 internalizing disorder, every 3 months over the course of 1 year. Symptoms and functioning of mothers and children improved significantly over time, with no between-group differences. However, children of mothers assigned to BSP had more outpatient mental health visits and were more likely to receive antidepressant medication. Mothers reported greater satisfaction with IPT-MOMS than BSP. Improvement in mothers' depressive symptoms was associated with improvement in child functioning in time-lagged fashion, with children improving 3 to 6 months after mothers improved. Antidepressant medication use and number of mental health visits received by children did not affect outcomes. IPT-MOMS and BSP demonstrated comparable beneficial effects on maternal depression. Children's functioning improved following maternal improvement, independent of youths' treatment. Children of mothers randomized to IPT-MOMS, compared with BSP, achieved comparable outcomes despite less follow-up treatment. Observation of lagged association between maternal improvement and change in child functioning should influence treatment planning for families. Clinical trial registration information-Psychotherapy for Depressed

Content Validity of the ADHD Rating Scale (ADHD RS-IV and Adult ADHD Self-Report Scale (ASRS in Phenylketonuria

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Kathleen W. Wyrwich PhD

2016-03-01

Full Text Available The ADHD Rating Scale (ADHD RS-IV; parent report and Adult ADHD Self-Rating Scale (ASRS; self-report are validated instruments for measuring symptoms of attention-deficit/hyperactivity disorder (ADHD. The objectives of this study were to elicit descriptions of phenylketonuria (PKU symptoms and assess content validity of these instruments in PKU. Parents (N = 15 of children with PKU (≥8 years old and adults with PKU (N=13 described PKU-related symptoms and commented on the scale’s clarity, comprehensiveness, and relevance to their experience with PKU. Most of the adults (84.6% and all of the children were on a phenylalanine-restricted diet, according to respondent report. The inattentiveness symptoms reported by participants mapped to the inattentive items of the questionnaires. Most participants felt the inattentive items were clear and relevant to their experience. Despite study design limitations, these results demonstrate the relevance of assessing inattentiveness in PKU, and both instruments achieved content validity for inattentive subscale items.

Maternal correlates of maternal child feeding practices: a systematic review.

Science.gov (United States)

McPhie, Skye; Skouteris, Helen; Daniels, Lynne; Jansen, Elena

2014-01-01

Establishing healthy eating habits early in life is one important strategy to combat childhood obesity. Given that early maternal child feeding practices have been linked to child food intake and weight, identifying the maternal correlates of maternal child feeding practices is important in order to understand the determinants of childhood obesity; this was the overall aim of the current review. Academic databases were searched for studies examining the relationship between maternal child feeding practices and parenting, personal characteristics and psychopathology of mothers with preschoolers. Papers were limited to those published in English, between January 2000 and June 2012. Only studies with mothers of normally developing children between the ages of 2 and 6 years were included. There were no restrictions regarding the inclusion of maternal nationality or socioeconomic status (SES). Seventeen eligible studies were sourced. Information on the aim, sample, measures and findings of these was summarised into tables. The findings of this review support a relationship between maternal controlling parenting, general and eating psychopathology, and SES and maternal child feeding practices. The main methodological issues of the studies reviewed included inconsistency in measures of maternal variables across studies and cross-sectional designs. We conclude that the maternal correlates associated with maternal child feeding practices are complex, and the pathways by which maternal correlates impact these feeding practices require further investigation. © 2012 John Wiley & Sons Ltd.

Risk assessment of medically assisted reproduction and advanced maternal ages in the development of Prader-Willi syndrome due to UPD(15)mat.

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Matsubara, K; Murakami, N; Fukami, M; Kagami, M; Nagai, T; Ogata, T

2016-05-01

Recent studies have suggested that disomic oocyte-mediated uniparental disomy 15 (UPD(15)mat) is increased in patients with Prader-Willi syndrome (PWS) born after medically assisted reproduction (MAR). However, it remains unknown whether the increase is primarily due to MAR procedure itself or advanced maternal childbearing ages as a predisposing factor for the disomic oocyte production. To examine this matter, we studied 122 naturally conceived PWS patients (PWS-NC group) and 13 MAR-conceived patients (PWS-MAR group). The relative frequency of disomic oocyte-mediated UPD(15)mat was significantly higher in PWS-MAR group than in PWS-NC group (7/13 vs 20/122, p = 0.0045), and the maternal childbearing ages were significantly higher in PWS-MAR group than in PWS-NC group [median (range), 38 (26-45) vs 30 (19-42), p = 0.0015]. However, the logistic regression analysis revealed no significant association between the occurrence of disomic oocyte-mediated UPD(15)mat and MAR, after adjusting for childbearing age (p = 0.25). Consistent with this, while the frequency of assisted reproductive technology (ART)-conceived livebirths was higher in the PWS patients than in the Japanese general population (6.4% vs 1.1%, p = 0.00018), the distribution of childbearing ages was significantly skewed to the increased ages in the PWS patients (p < 2.2 × 10(-16) ). These results argue against a positive association of MAR procedure itself with the development of UPD(15)mat. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Characteristics of phenylalanine hydroxylase gene mutations among patients with phenylketonuria from Linyi region of Shandong Province].

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Li, Huafeng; Li, Yongli; Zhang, Li

2017-06-10

To explore the characteristics of (PAH) gene mutations among patients with phenylketonuria (PKU) from Linyi area of Shandong Province. For 51 children affected with PKU and their parents, the 13 exons and their flanking intronic sequences of the PAH gene were directly sequenced with Sanger method. PAH gene mutations were detected in all of the 102 alleles of the patients, which included 31 types of mutations. Common mutations included R243Q (17/102, 16.67%), IVS4-1G to A (9/102, 8.82%), R241C (8/102, 7.84%), R111X (8/102, 7.84%), and V399V (8/102, 7.84%). In addition, two novel mutations, D101N, 345-347del, have been detected. The 31 types of mutations included missense, nonsense, deletion, and splicing mutations, which were mainly located in exons 7 (29, 28.43%), 11 (18, 17.65%), 3 (16, 15.69%) and 12 (13, 12.75%). Mutations of the PAH gene in Linyi region mainly distributed in exons 7, 11, and 3, and the most common mutation were R243Q. Two novel mutations, D101N and 345-347del, have been detected.

Hemophagocytic syndrome secondary to tuberculosis at 24-week gestation.

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Fernández, Alexandra Arteaga; de Velasco Pérez, David Fernández; Fournier, M C Jiménez; Moreno Del Prado, J C; Torras, B Paraíso; Cañete Palomo, M L

2017-01-01

Hemophagocytic syndrome is a life-threatening disease characterized by the uncontrolled activation of macrophages, resulting in hemophagocytosis of blood cells in the bone marrow. A 20-year-old gravida at 23-week and 5-day gestation was admitted to hospital to evaluate fever up to 104°F of unknown origin, moderate cytopenia, and elevated levels of liver enzymes. Bone marrow biopsy confirmed hemophagocytic syndrome, and polymerase chain reaction came back positive for Mycobacterium tuberculosis. Supportive care and tuberculosis treatment resulted in clinical improvement. At 27 weeks and 5 days, premature rupture of the membranes occurred, and because of the high probability of reactivating the hemophagocytic syndrome, a cesarean section was performed at 29-week and 2-day gestation. Hemophagocytic syndrome is an uncommon disease which rarely appears during pregnancy. Early diagnosis and treatment can save both maternal and fetal lives.

Phenylketonuria patients' and their parents' acceptance of the disease: multi-centre study.

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Witalis, Ewa; Mikoluc, Bożena; Motkowski, Radoslaw; Szyszko, Justyna; Chrobot, Agnieszka; Didycz, Bozena; Lange, Agata; Mozrzymas, Renata; Milanowski, Andrzej; Nowacka, Maria; Piotrowska-Depta, Mariola; Romanowska, Hanna; Starostecka, Ewa; Wierzba, Jolanta; Skorniewska, Magdalena; Wojcicka-Bartlomiejczyk, Barbara Iwona; Gizewska, Maria

2016-11-01

Phenylketonuria (PKU) still poses a therapeutic challenge for patients and medical professionals. The aim of the study was to assess both patients' and their parents' acceptance of the disease. The study included 218 PKU patients and 178 parents of PKU children who were enrolled in the study on the basis of questionnaire data. Regarding attitude towards the disease, our study demonstrated that 63 (28.9 %) PKU patients did not accept the disease. Patients who found accepting the disease difficult, more frequently perceived themselves as inferior/different in comparison with their peers. In total, 36 % of patients did not want their friends to be aware of their condition, while only 18 % of parents believed that their children's peers should not know about their disease. In total, 42 % of parents wanted to talk to other parents of PKU children and only 13 % to a doctor. Only 20 % of patients saw the need to discuss their condition with a doctor. In total, 8 % of children, regardless of age, and 14 % of parents preferred to talk to a psychologist. Our data demonstrated that disease acceptance played an essential role in patients' social integration. The study also indicated the need to overcome communication barriers between patients and their healthy peers and for patients to find the courage to be open about the disease. The importance of support groups for PKU families and the significance of strict cooperation between patients and their families with PKU treatment teams were also revealed.

Maternal Mortality in a Nigerian Maternity Hospital | Olopade ...

African Journals Online (AJOL)

Despite recent focus on maternal mortality in Nigeria, its rates remain unacceptably high in Nigeria. A retrospective case-control study was carried out at Adeoyo Maternity Hospital, Ibadan between January 2003 and December 2004. This was to determine the maternal mortality ratio in a secondary health facility, to identify ...

[Behaviour problems of children with Down syndrome in preschool-age - Results from the Heidelberg Down syndrome study].

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Sarimski, Klaus

2018-05-01

We report on the frequency and the correlations of behaviour problems among children with Down syndrome in preschool-age. As part of a longitudinal study 48 mothers of children with Down syndrome completed the German version of the “Strengths and Difficulties Questionnaire” (SDQ-D) and the Parenting Stress Inventory (PSI). The mothers were asked to fill out the questionnaires when the children had a mean age of five years. The results were compared to norms from children with typical development. Thirty per cent of the children with Down syndrome were rated as abnormal. Specifically, mean scores indicating problems with children of the same age and hyperactivity were elevated. A regression analysis predicting the total problem score of the SDQ-D revealed maternal educational level, optimistic attitude, and subjective parental stress at the age of one year and the degree of behavioural abnormalities at the age of three years as significant influential factors. Early intervention for Down syndrome children should include supporting parenting competence and coping skills in order to prevent behaviour problems.

Congenital varicella syndrome in a monochorionic diamniotic twin pregnancy.

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Villota, Vania A; Delgado, Julián; Pachajoa, Harry

2014-05-01

Congenital varicella syndrome encompasses a broad spectrum of malformations present in children of mothers who developed chickenpox during the first 20 weeks of gestation. We report a case of a monochorionic diamniotic twin pregnancy, with maternal exposure to chickenpox during the thirteenth week of gestation, which produced one symptomatic and one healthy child.

Environmental risk factors for sudden infant death syndrome in Japan.

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Hirabayashi, Masako; Yoshinaga, Masao; Nomura, Yuichi; Ushinohama, Hiroya; Sato, Seiichi; Tauchi, Nobuo; Horigome, Hitoshi; Takahashi, Hideto; Sumitomo, Naokata; Shiraishi, Hirohiko; Nagashima, Masami

2016-12-01

While the prevalence of sudden infant death syndrome (SIDS) has decreased worldwide, this decline has plateaued recently. Strategies are needed to resume the constant decrease of SIDS in Japan. A prospective electrocardiographic screening program for infants was performed between July 2010 and March 2011. Parents of 4319 infants were asked about environmental factors related to SIDS through questionnaires at a one-month medical checkup and one year. Parental awareness of prone position, smoke exposure, and breast feeding as environmental factors were 81.4 %, 69.0 %, and 47.8 %, respectively. The prevalence of laying infants exclusively in a supine position was 96.7 %. At the one-month medical checkup, smoking prevalence was 41.7 % in fathers and 2.1 % in mothers. Maternal smoking prevalence was significantly increased at one year after (p Japan. Smoking cessation programs should be further implemented for parents to decrease risks of SIDS in Japan. What is Known: • The prevalence of sudden infant death syndrome (SIDS) has decreased worldwide, however, this decline has plateaued recently. What is New: • Most infants were laid sleeping in the supine position (96.7 %) and were fed breast milk or a mix of expressed milk and formula (92.7 %), and 2.1 % of mothers smoked at the one-month medical checkup. • Maternal smoking prevalence significantly increased from the one-month medical checkup to one year later, and smoking mothers were more likely to feed infants by formula rather than breast milk. • Independent risk factors for new or continued maternal smoking habits included younger maternal age, maternal smoking habits at one month, and paternal smoking habits one year later.

Regional mapping of the phenylalanine hydroxylase gene and the phenylketonuria locus in the human genome

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Lidsky, A.S.; Law, M.L.; Morse, H.G.; Kao, F.T.; Rabin, M.; Ruddle, F.H.; Woo, S.L.C.

1985-09-01

Phenylketonuria (PKU) is an autosomal recessive disorder of amino acid metabolism caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase. To define the regional map position of the disease locus and the PAH gene on human chromosome 12, DNA was isolated from human-hamster somatic cell hybrids with various deletions of human chromosome 12 and was analyzed by Southern blot analysis using the human cDNA PAH clone as a hybridization probe. From these results, together with detailed biochemical and cytogenetic characterization of the hybrid cells, the region on chromosome 12 containing the human PAH gene has been defined as 12q14.3..-->..qter. The PAH map position on chromosome 12 was further localized by in situ hybridization of /sup 125/I-labeled human PAH cDNA to chromosomes prepared from a human lymphoblastoid cell line. Results of these experiments demonstrated that the region on chromosome 12 containing the PAH gene and the PKU locus in man is 12q22..-->..12q24.1. These results not only provide a regionalized map position for a major human disease locus but also can serve as a reference point for linkage analysis with other DNA markers on human chromosome 12.

Central precocious puberty in a 3 year-old girl with Phenylketonuria: a rare association?

Science.gov (United States)

2014-01-01

Background Central precocious puberty (CPP) and phenylketonuria (PKU) are two rare conditions, the latter being the rarer. To date, only one case featuring both these conditions has been reported, and hyperphenylalaninemia was assumed triggering CPP. Case presentation We present a 3.2 years old girl referred with a 12 months history of breast and pubic hair development, and vaginal discharge. Hyperphenylalaninemia had been identified by newborn screening and PKU subsequently confirmed by plasma amino acid and genetic analysis. Early dietary control of plasma phenylalanine had been excellent afterwards, resulting in phenylalanine concentrations consistently within the recommended range. Clinical scenario, hormonal assessment and imaging were in keeping with true idiopathic central precocious puberty. Treatment with long lasting gonadotropin-releasing hormone analogue led to regression of secondary sexual characteristics. Conclusion We describe for the first time CPP in a girl affected with PKU but with persistently well controlled blood phenylalanine concentrations. This finding is in contrast to a previous report which suggested persistently high phenylalaninemia levels as potential trigger for CPP in PKU patients. Our report, together with the lack of evidence in published cohort studies of children with PKU, strongly suggests this rare association is coincidental and independent of the presence of severe hyperphenylalaninemia. PMID:24773629

Regional mapping of the phenylalanine hydroxylase gene and the phenylketonuria locus in the human genome

International Nuclear Information System (INIS)

Lidsky, A.S.; Law, M.L.; Morse, H.G.; Kao, F.T.; Rabin, M.; Ruddle, F.H.; Woo, S.L.C.

1985-01-01

Phenylketonuria (PKU) is an autosomal recessive disorder of amino acid metabolism caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase. To define the regional map position of the disease locus and the PAH gene on human chromosome 12, DNA was isolated from human-hamster somatic cell hybrids with various deletions of human chromosome 12 and was analyzed by Southern blot analysis using the human cDNA PAH clone as a hybridization probe. From these results, together with detailed biochemical and cytogenetic characterization of the hybrid cells, the region on chromosome 12 containing the human PAH gene has been defined as 12q14.3→qter. The PAH map position on chromosome 12 was further localized by in situ hybridization of 125 I-labeled human PAH cDNA to chromosomes prepared from a human lymphoblastoid cell line. Results of these experiments demonstrated that the region on chromosome 12 containing the PAH gene and the PKU locus in man is 12q22→12q24.1. These results not only provide a regionalized map position for a major human disease locus but also can serve as a reference point for linkage analysis with other DNA markers on human chromosome 12

Adaptive Behaviour in Angelman Syndrome: Its Profile and Relationship to Age

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Gasca, C. Brun; Obiols, J. E.; Bonillo, A.; Artigas, J.; Lorente, I.; Gabau, E.; Guitart, M.; Turk, J.

2010-01-01

Background: Angelman syndrome (AS) is a neurodevelopmental disorder usually caused by an anomaly in the maternally inherited chromosome 15. The main features are severe intellectual disability, speech impairment, ataxia, epilepsy, sleep disorder and a behavioural phenotype that reportedly includes happy disposition, attraction to/fascination with…

Investigation on Down's syndrome in the children living in high background radiation area

International Nuclear Information System (INIS)

Zha Yongru

1989-01-01

After the survey in 1975 and 1979 of Down's syndrome in the children living in high background radiation area, we made a follow-up investigation in 1985 and 1986. All the obtained data are analysed. 25258 children in high background radiation area were examined and 22 children with Down's syndrome were identified, the morbidity rate being 0.87%. 21837 children in control area were examined and four children with Down's syndrome were identified, the morbidity being 0.18%. There was a statistically significant difference between the two groups. It was noted that the occurrence of Down's syndrome was related to the maternal age but there was no evidence suggesting a close relationship between high background radiation and the development of Down's syndrome

Early-onset behavioral and neurochemical deficits in the genetic mouse model of phenylketonuria.

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Fiori, Elena; Oddi, Diego; Ventura, Rossella; Colamartino, Marco; Valzania, Alessandro; D'Amato, Francesca Romana; Bruinenberg, Vibeke; van der Zee, Eddy; Puglisi-Allegra, Stefano; Pascucci, Tiziana

2017-01-01

Phenylketonuria (PKU) is one of the most common human inborn errors of metabolism, caused by phenylalanine hydroxylase deficiency, leading to high phenylalanine and low tyrosine levels in blood and brain causing profound cognitive disability, if untreated. Since 1960, population is screened for hyperphenylalaninemia shortly after birth and submitted to early treatment in order to prevent the major manifestations of the disease. However, the dietetic regimen (phenylalanine free diet) is difficult to maintain, and despite the recommendation to a strict and lifelong compliance, up to 60% of adolescents partially or totally abandons the treatment. The development and the study of new treatments continue to be sought, taking advantage of preclinical models, the most used of which is the PAHenu2 (BTBR ENU2), the genetic murine model of PKU. To date, adult behavioral and neurochemical alterations have been mainly investigated in ENU2 mice, whereas there are no clear indications about the onset of these deficiencies. Here we investigated and report, for the first time, a comprehensive behavioral and neurochemical assay of the developing ENU2 mice. Overall, our findings demonstrate that ENU2 mice are significantly smaller than WT until pnd 24, present a significant delay in the acquisition of tested developmental reflexes, impaired communicative, motor and social skills, and have early reduced biogenic amine levels in several brain areas. Our results extend the understanding of behavioral and cerebral abnormalities in PKU mice, providing instruments to an early preclinical evaluation of the effects of new treatments.

Inactivation of the maternal fragile X gene results in sensitization of GABAB receptor function in the offspring.

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Zupan, Bojana; Toth, Miklos

2008-12-01

Fragile X syndrome is an X-linked disorder caused by the inactivation of the FMR1 gene, with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities, and hyperactivity. Although fragile X syndrome is considered a typical Mendelian disorder, we have recently reported that the environment, specifically the fmr1(+/-) or fmr1(-/-) [H or knockout (KO)] maternal environment, elicits on its own a partial fragile X-like phenotype and can contribute to the overall phenotype of fmr1(-/0) (KO) male offspring. Genetically fmr1(+/0) (WT) males born to H females (H(maternal) > WT(offspring)), similar to KO male offspring born to H and KO mothers (H > KO and KO > KO), exhibit locomotor hyperactivity. These mice also showed reduced D(2) autoreceptor function, indicating a possible diminished feedback inhibition of dopamine (DA) release in the nigrostriatal and mesolimbic systems. The GABAergic system also regulates DA release, in part via presynaptic GABA(B) receptors (Rs) located on midbrain dopaminergic neurons. Here, we show that the locomotor inhibitory effect of the GABA(B)R agonist baclofen [4-amino-3-(4-chlorophenyl)-butanoic acid] is enhanced in all progeny of mutant mothers (H > WT, H > KO, and KO > KO) compared with WT > WT mice, irrespective of their own genotype. However, increased sensitivity to baclofen was selective and limited to the locomotor response because the muscle-relaxant and sedative effects of the drug were not altered by the maternal environment. These data show that GABA(B)R sensitization, traditionally induced pharmacologically, can also be elicited by the fmr1-deficient maternal environment.

A link between thrifty phenotype and maternal care across two generations of intercrossed mice.

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Bruno Sauce

Full Text Available Maternal effects are causal influences from mother to offspring beyond genetic information, and have lifelong consequences for multiple traits. Previously, we reported that mice whose mothers did not nurse properly had low birth weight followed by rapid fat accumulation and disturbed development of some organs. That pattern resembles metabolic syndromes known collectively as the thrifty phenotype, which is believed to be an adaptation to a stressful environment which prepares offspring for reduced nutrient supply. The potential link between maternal care, stress reactivity, and the thrifty phenotype, however, has been poorly explored in the human and animal literature: only a couple of studies even mention (much less, test these concepts under a cohesive framework. Here, we explored this link using mice of the parental inbred strains SM/J and LG/J-who differ dramatically in their maternal care-and the intercrossed generations F1 and F2. We measured individual differences in 15 phenotypes and used structural equation modeling to test our hypotheses. We found a remarkable relationship between thrifty phenotype and lower quality of maternal behaviors, including nest building, pup retrieval, grooming/licking, and nursing. To our knowledge, this is the first study to show, in any mammal, a clear connection between the natural variation in thrifty phenotype and maternal care. Both traits in the mother also had a substantial effect on survival rate in the F3 offspring. To our surprise, however, stress reactivity seemed to play no role in our models. Furthermore, the strain of maternal grandmother, but not of paternal grandmother, affected the variation of maternal care in F2 mice, and this effect was mediated by thrifty phenotype in F2. Since F1 animals were all genetically identical, this finding suggests that maternal effects pass down both maternal care and thrifty phenotype in these mice across generations via epigenetic transmission.

Prenatal diagnosis and prognosis of triple X syndrome: 47, XXX.

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Ben Hamouda, H; Mkacher, N; Elghezal, H; Bannour, H; Kamoun, M; Soua, H; Saad, A; Souissi, M M; Sfar, M T

2009-11-01

Triple X syndrome is a relatively common sex chromosomal abnormality occurring in 0,1% of live-born female infants. Most of these infants have a normal phenotype and only a few cases with 47, XXX karyotype have congenital malformations. We report three cases of triple X syndrome that were diagnosed prenatally by genetic amniocentesis for advanced maternal age and have been observed from birth to age of 3 to 12 years. A description of their growth and development is presented. The birth weight was normal in all patients and one of them had facial dysmorphism with right microphtalmia and auricular septal defect. During the first 2 years of life, the neuromotor development of these infants was not distinguishable from chromosomally normal children. By 3 years of age, two patients have a moderate developmental delay in speech and language. One girl 12-year-old had normal schooling. The diagnosis of the triple X syndrome can be never made because clinical demonstrations are not rather important to arouse the demand of a karyotype. Prenatal diagnosis is often made in front of the advanced maternal age. Expectant parents must be counseled as to the significance of this 47, XXX karyotype and prognostic information must be given.

Neuromyelitis optica in pregnancy complicated by posterior reversible encephalopathy syndrome, eclampsia and fetal death.

Science.gov (United States)

Igel, Catherine; Garretto, Diana; Robbins, Matthew S; Swerdlow, Michael; Judge, Nancy; Dayal, Ashlesha

2015-03-01

Neuromyelitis optica (NMO) is a demyelinating syndrome characterized by optic neuritis and acute myelitis with poor recovery and a progressive course. We report a poor outcome complicated by posterior reversible encephalopathy syndrome (PRES) and eclampsia and review available literature and current evidence for anticipation of adverse fetal and maternal effects. After a pregnancy complicated by multiple admissions for painful NMO exacerbations, a primiparous patient with seropositive NMO presented at 31 + 3/7 weeks with eclampsia, HELLP and subsequent fetal death. MRI confirmed PRES. NMO may be associated with eclampsia and leads to adverse maternal and fetal outcomes. Posited mechanisms include antibody-mediated placental damage and a heightened risk of eclampsia-associated PRES. Further characterization of the course of NMO and its relationship with pregnancy outcomes in larger series would be invaluable.

Serum Lycopene Concentrations and Associations with Clinical Outcomes in a Cohort of Maternal-Infant Dyads.

Science.gov (United States)

Hanson, Corrine; Lyden, Elizabeth; Furtado, Jeremy; Van Ormer, Matthew; White, Kimberly; Overby, Nina; Anderson-Berry, Ann

2018-02-13

Oxidative stress has been associated with adverse neonatal outcomes, and many carotenoids, including lycopene, potentially have antioxidant properties. The objective of this analysis was to explore the associations between serum lycopene concentrations, including lycopene isomers, and maternal-newborn outcomes. Maternal and cord blood samples were collected in 180 mother-infant pairs. Serum of total lycopene as well as the cis - and trans -isomers concentrations were measured using HPLC (High Performance Liquid Chromatography). Descriptive statistics were calculated; Spearman coefficients were used to assess correlations between maternal and cord concentrations. The relationship between lycopene concentration and outcomes were evaluated with linear and logistic regression models, with adjustment for relevant confounders. A p ≤ 0.05 was considered statistically significant. Maternal and cord serum lycopene concentrations were positively correlated for total lycopene ( r = 0.30, p lycopene ( r = 0.29, p = 0.0002); and trans -lycopene ( r = 0.32, p lycopene were significantly lower in mothers whose infants developed respiratory distress syndrome compared to those who did not (0.336 ± 0.171 vs. 0.445 ± 0.238 µmol/L, p = 0.04) and also in mothers whose babies were admitted to the newborn intensive care unit compared to those who were not (0.380 ± 0.202 vs. 0.458 ± 0.244 µmol/L, p = 0.04). Conversely, cord concentrations of trans -lycopene were significantly higher in infants who developed RDS (Respiratory Distress Syndrome) (0.023 ± 0.012 vs. 0.016 ± 0.012, p = 0.007 for RDS vs. no RDS), and a similar pattern was seen NICU admission (0.023 ± 0.016 vs. 0.015 ± 0.009 µmol/L for NICU (Newborn Intensive Care Unit) admission vs. no NICU admission, p = 0.007). Maternal concentrations of total and cis -lycopene were positively associated with infant birth weight, length and head circumference after adjustment for relevant confounders. As serum carotenoids

Maternal Super Obesity and Neonatal Morbidity after Term Cesarean Delivery.

Science.gov (United States)

Smid, Marcela C; Vladutiu, Catherine J; Dotters-Katz, Sarah K; Manuck, Tracy A; Boggess, Kim A; Stamilio, David M

2016-10-01

Objective To estimate the association between maternal super obesity (body mass index [BMI] ≥ 50 kg/m(2)) and neonatal morbidity among neonates born via cesarean delivery (CD). Methods Retrospective cohort of singleton neonates delivered via CD ≥ 37 weeks in the Maternal-Fetal Medicine Unit Cesarean Registry. Maternal BMI at delivery was stratified as 18.5 to 29.9 kg/m(2), 30 to 39.9 kg/m(2), 40 to 49.9 kg/m(2), and ≥ 50 kg/m(2). Primary outcomes included acute (5-minute Apgar score neonatal injury, and/or transient tachypnea of the newborn) and severe (grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, seizure, respiratory distress syndrome, hypoxic ischemic encephalopathy, meconium aspiration, ventilator support ≥ 2 days, sepsis and/or neonatal death) neonatal morbidity. Odds of neonatal morbidity were estimated for each BMI category adjusting for clinical and operative characteristics. Results Of 41,262 maternal-neonatal dyads, 36% of women were nonobese, 49% had BMI of 30 to 39.9 kg/m(2), 12% had BMI of 40 to 49.9 kg/m(2), and 3% were super obese. Compared with nonobese women, super obese women had twofold odds of acute (5 vs. 10%; adjusted odds ratio [aOR]: 1.81, 95% confidence interval [CI]: 1.59-2.73) and severe (3 vs. 6%; aOR: 2.08; 95% CI: 1.59-2.73) neonatal morbidity. Conclusion Among term infants delivered via CD, maternal super obesity is associated with increased risk of neonatal morbidity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Parenting Young Children with and without Fragile X Syndrome

Science.gov (United States)

Sterling, Audra; Barnum, Leah; Skinner, Debra; Warren, Steven F.; Fleming, Kandace

2012-01-01

The purpose of this study was to examine maternal parenting styles across age-matched siblings using a within-family design, in which one child has Fragile X syndrome. Thirteen families participated; children were aged 16 to 71 months. Mothers completed several videotaped activities with each child separately as well as an interview. Mothers used…

Evaluation of trace element and mineral status and related to levels of amino acid in children with phenylketonuria.

Science.gov (United States)

Gok, Fazilet; Ekin, Suat; Dogan, Murat

2016-07-01

The aim of the present study was to examine trace elements (Zn, Cu, Mn, Se, Fe, Co, Cr, Ni, Cd, Pb), minerals (Ca, Mg, K), amino acids status in children with phenylketonuria and also whether they were correlated with each other in phenylketonuric patients. It has been found out that the HPA group was significantly lower than the control group with regards to Zn, Se, K, Ca, Mg and Zn/Cr levels (p<0.001, p<0.01, p<0.001, p<0.01, p<0.01 and p<0.001 respectively). In the patients with HPA, significantly strong positive correlations were observed between magnesium and calcium (r=0.791; p=0.001), also, indicates negative significant correlation between the concentrations of magnesium and phenylalanine (r=-0.591; p=0.026). The results of this study showed that, in the HPA group, phenylalanine-Mg relationship found, the presence of disease will in the evaluation of phenylalanine and other amino acids, together with the value of magnesium is required to consider. Copyright © 2016 Elsevier B.V. All rights reserved.

Down Syndrome Temperament: The Stereotype at Middle Childhood and Adolescence.

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Gunn, Pat; Cuskelly, Monica

1991-01-01

Behavioral ratings by mothers and teachers of 94 children with Down's Syndrome (between 8 and 14 years of age) indicated general support for the amiable personality stereotype, but ratings of low persistence were associated with maternal impressions of difficulty. There was little agreement between mothers and teachers regarding individual child…

Atypical presentation of HELLP syndrome: clinical case report

Directory of Open Access Journals (Sweden)

Juan Manuel Tobar Parra

2017-12-01

Full Text Available Objective: To describe a case of HELLP syndrome with atypical presentation form. Background: HELLP syndrome is a complication of preeclampsia, characterized by: haemolysis, elevation of liver enzymes and thrombocytopenia; Can present atypical, without hypertension or proteinuria, 10-20% of the cases. Case report: 38 year old female patient, with a pregnancy of 38.5 weeks of gestation, treated at the Hospital Universitario San José de Popayán (Colombia. Atypical HELLP syndrome is diagnosed in a pregnant woman with thrombocytopenia, impaired liver enzymes, but no evidence of proteinuria or hypertension. Gestation is terminated by cesarean section and magnesium sulfate is given for 24 hours, with adequate post-surgical evolution, clinical improvement of the symptomatology presented, normalization of liver enzymes and platelet elevation. Conclusion: Knowledge of this syndrome, although of rare occurrence, allows a fast action, an effective diagnosis and treatment, to avoid morbidity and greater maternal fetal mortality.

Reconfiguring Maternity Care?

DEFF Research Database (Denmark)

Johannsen, Nis

This dissertation constitutes a reflection on two initiatives seeking to reconfigure maternity care. One initiative sought to digitalise maternity records and included a pilot run of an electronic maternity record in a Danish county. The other consisted of a collaboration between a maternity ward...... at a hospital and a group of researchers which included me. Both initiatives involved numerous seemingly different interests that were held together and related to reconfiguring maternity care. None of the initiatives can unequivocally be labelled a success, as neither managed to change maternity care, at least...... experimental designs are constructed. The consequences and the politics of the proposed changes are engaged with in laboratory manner through collaborative development of the designs and through exposing them to members of field of maternity care...

[The relationship between early neo-maternal exposure, and maternal attachment, maternal self-esteem and postpartum depression in the mothers of NICU infants].

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Ahn, Young-Mee; Kim, Mi-Ran

2005-08-01

This study was performed to investigate the quantities of three neo-maternal exposures; visiting frequency, auditory contact and physical contact, and to examine the relationship between the quantities of each exposure and maternal attachment, maternal self-esteem and postpartum depression in 40 mothers of NICU babies during the first week in the NICU. Each neo-maternal exposure was counted at every mother's visit to the newborn and maternal attachment, maternal self-esteem and postpartum depression were measured using the maternal attachment inventory, the maternal self-report inventory and Edinburgh Postpartum Depression Scale (EPDS) on the first and seventh day in the NICU. The Mean of each neo-maternal exposure was 8.77(2.81) for the visiting frequency, 5.82(3.66) for the auditory contact and 5.60(2.89) for the physical contact during 7 days in the NICU. No significant changes were found in the scores of maternal attachment, maternal self-esteem and postpartum depression between the first and the seventh day in the NICU. The quantities of neo-maternal exposures were positively related to the scores of maternal attachment and maternal self-esteem but not related to postpartum depression. The results of the study suggest the lack of early neo-maternal exposure in cases of NICU hospitalization negate its beneficial effects on maternal psychological well-being in increasing maternal attachment and self-esteem. More efforts are needed for the neo-maternal interaction and the reevaluation of NICU visitation hours in order to promote maternal-infant interaction.

Clinical characteristics of mirror syndrome: a comparison of 10 cases of mirror syndrome with non-mirror syndrome fetal hydrops cases.

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Hirata, Go; Aoki, Shigeru; Sakamaki, Kentaro; Takahashi, Tsuneo; Hirahara, Fumiki; Ishikawa, Hiroshi

2016-01-01

To investigate clinical features of mirror syndrome. We retrospectively reviewed 71 cases of fetal hydrops with or without mirror syndrome, and compared with respect to maternal age, the body mass index, the primipara rate, the gestational age at delivery, the timing of fetal hydrops onset, the severity of fetal edema, placental swelling, the laboratory data and the fetal mortality. The data are expressed as the medians. Mirror syndrome developed in 29% (10/35) of the cases with fetal hydrops. In mirror group, the onset time of fetal hydrops was significantly earlier (29 weeks versus 31 weeks, p = 0.011), and the severity of fetal hydrops (fetal edema/biparietal diameter) was significantly higher than non-mirror group (0.23 versus 0.16, p < 0.001). There was significantly higher serum human chorionic gonadotropin (hCG) (453,000 IU/L versus 80,000 IU/L, p < 0.001) and lower hemoglobin (8.9 g/dL versus 10.1 g/dL, p =0.002), hypoalbuminemia (2.3 mg/dL versus 2.7 mg/dL, p = 0.007), hyperuricemia (6.4 mg/dL versus 5.0 mg/dL, p = 0.043) in mirror group. Mirror syndrome is occurred frequently in early and severe fetal hydrops and cause hemodilution and elevation of serum hCG.

Cleft lip and palate: an adverse pregnancy outcome due to undiagnosed maternal and paternal coeliac disease.

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Arakeri, Gururaj; Arali, Veena; Brennan, Peter A

2010-07-01

Development of orofacial component involves a complex series of events. Any insult to this significant event can lead to various orofacial cleft defects. The main categories among orofacial clefts are isolated cleft palate and cleft lip with or without cleft palate. There have been many factors implicated in the development of the anomaly. The environmental factors which contribute and the genes which predispose to the condition remain obscure despite decades of research. Though it is generally agreed that folic acid deficiency is a contributory factor for non-syndromic cleft lip and palate, fewer concerns are directed towards the role for maternal/paternal nutrition in orofacial cleft origin. However, previously undescribed, here we consider the potential influence of maternal and paternal coeliac disease on the etiology of non-syndromic cleft lip and palate as an unfavorable pregnancy outcome. We postulated this relationship based on our observation, study and an empirical survey, and could be due either to (I) folic acid mal absorption (II) a genetically mediated genomic imprinting system. Copyright 2010 Elsevier Ltd. All rights reserved.

Hemophagocytic syndrome secondary to tuberculosis at 24-week gestation

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Alexandra Arteaga Fernández

2017-01-01

Full Text Available Hemophagocytic syndrome is a life-threatening disease characterized by the uncontrolled activation of macrophages, resulting in hemophagocytosis of blood cells in the bone marrow. A 20-year-old gravida at 23-week and 5-day gestation was admitted to hospital to evaluate fever up to 104°F of unknown origin, moderate cytopenia, and elevated levels of liver enzymes. Bone marrow biopsy confirmed hemophagocytic syndrome, and polymerase chain reaction came back positive for Mycobacterium tuberculosis. Supportive care and tuberculosis treatment resulted in clinical improvement. At 27 weeks and 5 days, premature rupture of the membranes occurred, and because of the high probability of reactivating the hemophagocytic syndrome, a cesarean section was performed at 29-week and 2-day gestation. Hemophagocytic syndrome is an uncommon disease which rarely appears during pregnancy. Early diagnosis and treatment can save both maternal and fetal lives.

Maternal-fetal cholesterol transport in the second half ofmouse pregnancy does not involve LDL receptor-related protein 2

NARCIS (Netherlands)

Zwier, Mathijs V; Baardman, Maria E; van Dijk, Theo H; Jurdzinski, Angelika; Wisse, Lambertus J; Bloks, Vincent W; Berger, Rolf M F; DeRuiter, Marco C; Groen, Albert K; Plösch, Torsten

AimLDL receptor-related protein type 2 (LRP2) is highly expressed on both yolk sac and placenta. Mutations in the corresponding gene are associated with severe birth defects in humans, known as Donnai-Barrow syndrome. We here characterized the contribution of LRP2 and maternal plasma cholesterol

Congenital varicella syndrome in a monochorionic diamniotic twin pregnancy

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Vania A Villota

2014-01-01

Full Text Available Congenital varicella syndrome encompasses a broad spectrum of malformations present in children of mothers who developed chickenpox during the first 20 weeks of gestation. We report a case of a monochorionic diamniotic twin pregnancy, with maternal exposure to chickenpox during the thirteenth week of gestation, which produced one symptomatic and one healthy child.

Maternal anxiety, maternal sensitivity, and attachment

NARCIS (Netherlands)

Stevenson-Hinde, Joan; Chicot, Rebecca; Shouldice, Anne; Hinde, Camilla A.

2016-01-01

Previous research has related maternal anxiety to insecurity of attachment. Here we ask whether different aspects of maternal sensitivity mediate this link. From a community sample of intact families with 1-3 children, mothers with 4.5-year-olds were selected for low, medium, or high anxiety

Maternal anxiety, maternal sensitivity, and attachment

NARCIS (Netherlands)

Stevenson-Hinde, J.; Chicot, R.; Schouldice, A.; Hinde, C.A.

2013-01-01

Previous research has related maternal anxiety to insecurity of attachment. Here we ask whether different aspects of maternal sensitivity mediate this link. From a community sample of intact families with 1-3 children, mothers with 4.5-year-olds were selected for low, medium, or high anxiety levels

IMAGe syndrome: clinical and genetic implications based on investigations in three Japanese patients.

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Kato, Fumiko; Hamajima, Takashi; Hasegawa, Tomonobu; Amano, Naoko; Horikawa, Reiko; Nishimura, Gen; Nakashima, Shinichi; Fuke, Tomoko; Sano, Shinichirou; Fukami, Maki; Ogata, Tsutomu

2014-05-01

Arboleda et al. have recently shown that IMAGe (intra-uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities) syndrome is caused by gain-of-function mutations of maternally expressed gene CDKN1C on chromosome 11p15.5. However, there is no other report describing clinical findings in patients with molecularly studied IMAGe syndrome. Here, we report clinical and molecular findings in Japanese patients. We studied a 46,XX patient aged 8·5 years (case 1) and two 46,XY patients aged 16·5 and 15·0 years (cases 2 and 3). Clinical studies revealed not only IMAGe syndrome-compatible phenotypes in cases 1-3, but also hitherto undescribed findings including relative macrocephaly and apparently normal pituitary-gonadal endocrine function in cases 1-3, familial glucocorticoid deficiency (FGD)-like adrenal phenotype and the history of oligohydramnios in case 2, and arachnodactyly in case 3. Sequence analysis of CDKN1C, pyrosequencing-based methylation analysis of KvDMR1 and high-density oligonucleotide array comparative genome hybridization analysis for chromosome 11p15.5 were performed, showing an identical de novo and maternally inherited CDKN1C gain-of-function mutation (p.Asp274Asn) in cases 1 and 2, respectively, and no demonstrable abnormality in case 3. The results of cases 1 and 2 with CDKN1C mutation would argue the following: [1] relative macrocephaly is consistent with maternal expression of CDKN1C in most tissues and biparental expression of CDKN1C in the foetal brain; [2] FGD-like phenotype can result from CDKN1C mutation; and [3] genital abnormalities may primarily be ascribed to placental dysfunction. Furthermore, lack of CDKN1C mutation in case 3 implies genetic heterogeneity in IMAGe syndrome. © 2013 John Wiley & Sons Ltd.

Stevens Johnson Syndrome and Toxic Epidermal Necrolysis: Maternal and Foetal Outcomes in Twenty-Two Consecutive Pregnant HIV Infected Women.

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Lauren Knight

Full Text Available Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN form a spectrum of a rare and life-threatening cutaneous drug reaction. SJS/TEN in pregnancy poses largely unknown risk factors and outcomes for both the mother and foetus compared to the general population.We conducted a study of consecutive pregnant women admitted to single tertiary referral centre in South Africa with SJS/TEN over a 3 year period. They were all managed by the same medical team using the same protocols. We evaluated their underlying illnesses, offending drugs and the course of pregnancy and outcomes to determine factors influencing maternal and foetal outcomes.We identified twenty-two women who developed SJS/TEN while pregnant, all of them HIV-infected. Their median age was 29 years. The majority 16/22 (73% had SJS, the milder variant of the disease affecting < 10% body surface area. Nevirapine was the offending drug in 21/22 (95% cases. All 22 of the mothers survived with 3/22 (14% developing postpartum sepsis. Pregnancy outcomes were known in 18/22 women and 9/18 (50% babies were delivered by caesarean section. There were 2 foetal deaths at 21 and 31 weeks respectively and both were associated with post-partum sepsis. Postnatal complications occurred in 5 cases, 3 involving the respiratory system and the other two being low birth weight deliveries. Eight placentae and one foetus were sent for histology and none showed macroscopic or microscopic features of SJS/TEN. On follow-up, only 12/20 children were tested for HIV at 6 weeks post-delivery and none of them were HIV-infected. All had received prophylactic ARVs including nevirapine.TEN, the severe form of the disease, was associated with poorer foetal outcomes. SJS/TEN-associated mortality is not increased in HIV-infected pregnant women. Maternal SJS/TEN does not seem to commonly manifest in the foetus.

Effects of maternal confidence and competence on maternal parenting stress in newborn care.

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Liu, Chien-Chi; Chen, Yueh-Chih; Yeh, Yen-Po; Hsieh, Yeu-Sheng

2012-04-01

This paper is a report of a correlational study of the relations of maternal confidence and maternal competence to maternal parenting stress during newborn care. Maternal role development is a cognitive and social process influenced by cultural and family contexts and mother and child characteristics. Most knowledge about maternal role development comes from western society. However, perceptions of the maternal role in contemporary Taiwanese society may be affected by contextual and environmental factors. A prospective correlational design was used to recruit 372 postpartum Taiwanese women and their infants from well-child clinics at 16 health centres in central Taiwan. Inclusion criteria for mothers were gestational age >37 weeks, ≥18 years old, and healthy, with infants maternal confidence, maternal competence and self-perceived maternal parenting stress. After controlling for maternal parity and infant temperament, high maternal confidence and competence were associated with low maternal parenting stress. Maternal confidence influenced maternal parenting stress both directly and indirectly via maternal competence. To assist postpartum women in infant care programmes achieve positive outcomes, nurses should evaluate and bolster mothers' belief in their own abilities. Likewise, nurses should not only consider mothers' infant care skills, but also mothers' parity and infant temperament. Finally, it is crucial for nurses and researchers to recognize that infant care programmes should be tailored to mothers' specific maternal characteristics. © 2011 The Authors. Journal of Advanced Nursing © 2011 Blackwell Publishing Ltd.

Obstetrical complications in dichorionic twin pregnancies in women with polycystic ovary syndrome

DEFF Research Database (Denmark)

Jonsdottir, Fjola; Nilas, Lisbeth; Andreasen, Kirsten R

2017-01-01

INTRODUCTION: Both women with polycystic ovary syndrome (PCOS) and women with twin pregnancies have increased risk of adverse pregnancy outcome. The aim of this study was to investigate the impact of PCOS and maternal androgen levels on the outcome of dichorionic twin pregnancy. MATERIAL...

Maternal Diabetes in Pregnancy: Early and Long-Term Outcomes on the Offspring and the Concept of “Metabolic Memory”

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Akadiri Yessoufou

2011-01-01

Full Text Available The adverse outcomes on the offspring from maternal diabetes in pregnancy are substantially documented. In this paper, we report main knowledge on impacts of maternal diabetes on early and long-term health of the offspring, with specific comments on maternal obesity. The main adverse outcome on progenies from pregnancy complicated with maternal diabetes appears to be macrosomia, as it is commonly known that intrauterine exposure to hyperglycemia increases the risk and programs the offspring to develop diabetes and/or obesity at adulthood. This “fetal programming”, due to intrauterine diabetic milieu, is termed as “metabolic memory”. In gestational diabetes as well as in macrosomia, the complications include metabolic abnormalities, degraded antioxidant status, disrupted immune system and potential metabolic syndrome in adult offspring. Furthermore, there is evidence that maternal obesity may also increase the risk of obesity and diabetes in offspring. However, women with GDM possibly exhibit greater macrosomia than obese women. Obesity and diabetes in pregnancy have independent and additive effects on obstetric complications, and both require proper management. Management of gestational diabetes mellitus and maternal obesity is essential for maternal and offspring's good health. Increasing physical activity, preventing gestational weight gain, and having some qualitative nutritional habits may be beneficial during both the pregnancy and offspring's future life.

[Pregnancy in patients with renal transplantation: maternal and fetal morbidity].

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Romero Arauz, Juan Fernando; Ayala Méndez, José Antonio; Jiménez Solís, Guillermo

2008-11-01

Preeclampsia is a multisystemic syndrome with unknown etiology and characterized by abnormal vascular placentation response. Patients with renal transplantation restore them fertility 10 months after the intervention. To evaluate incidence of preeclampsia and maternal-perinatal outcome in patients with renal transplantation. Comparative, observational and retrospective study performed in pregnant patients with renal transplantation, from December 1999 to April 2008 at Perinatology of Hypertensive Diseases Department of the Unidad Medica de Alta Especialidad de Ginecoobstetricia Luis Castelazo Ayala, IMSS. Davison' guide, descriptive statistic, and Fischer exact test were used. Thirty patients were analyzed, 27 cases satisfy Davison's recommended guidelines, and the rest did not achieve these criteria (p = 0.001). Preeclampsia occurred in 15 cases (50%), preterm delivery in 15 (50%), and fetal growth restriction in 6 (20%). Among the 11 patients with previous chronic hypertension, 8 developed superimposed preeclampsia (72%), and 9 had delivery before 37 weeks of gestation (82%). Malfunction of renal transplantation, before pregnancy, was associated with maternal and perinatal poor outcome (p = 0.006). There were no maternal deaths, but one perinatal (3%) Successful pregnancy is possible in patients with renal transplantation, however there is a high risk of preeclampsia, infection, and fetal growth restriction. Patients with renal transplantation must fulfill Davison's pre-pregnancy guidelines.

Maternal Depression and Youth Internalizing and Externalizing Symptomatology: Severity and Chronicity of Past Maternal Depression and Current Maternal Depressive Symptoms

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O’Connor, Erin E.; Langer, David A.; Tompson, Martha C.

2017-01-01

Maternal depression is a well-documented risk factor for youth depression, and taking into account its severity and chronicity may provide important insight into the degree of risk conferred. This study explored the degree to which the severity/chronicity of maternal depression history explained variance in youth internalizing and externalizing symptoms above and beyond current maternal depressive symptoms among 171 youth (58% male) ages 8 to 12 over a span of three years. Severity and chronicity of past maternal depression and current maternal depressive symptoms were examined as predictors of parent-reported youth internalizing and externalizing symptomatology, as well as youth self-reported depressive symptoms. Severity and chronicity of past maternal depression did not account for additional variance in youth internalizing and externalizing symptoms at Time 1 beyond what was accounted for by maternal depressive symptoms at Time 1. Longitudinal growth curve modeling indicated that prior severity/chronicity of maternal depression predicted levels of youth internalizing and externalizing symptoms at each time point when controlling for current maternal depressive symptoms at each time point. Chronicity of maternal depression, apart from severity, also predicted rate of change in youth externalizing symptoms over time. These findings highlight the importance of screening and assessing for current maternal depressive symptoms, as well as the nature of past depressive episodes. Possible mechanisms underlying the association between severity/chronicity of maternal depression and youth outcomes, such as residual effects from depressive history on mother–child interactions, are discussed. PMID:27401880

Syndrome of arachnomelia in Simmental cattle

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Weppert Myriam

2008-10-01

Full Text Available Abstract Background The syndrome of arachnomelia is an inherited malformation mainly of limbs, back and head in cattle. At present the arachnomelia syndrome has been well known mainly in Brown Swiss cattle. Nevertheless, the arachnomelia syndrome had been observed in the Hessian Simmental population during the decade 1964–1974. Recently, stillborn Simmental calves were observed having a morphology similar to the arachnomelia syndrome. The goal of this work was the characterization of the morphology and genealogy of the syndrome in Simmental to establish the basis for an effective management of the disease. Results The first pathologically confirmed arachnomelia syndrome-cases in the current Simmental population appeared in the year 2005. By 2007, an additional 140 calves with the arachnomelia syndrome were identified. The major pathological findings were malformed bones affecting the head, long bones of the legs and the vertebral column. It could be shown that, with the exception of two cases that were considered as phenocopies, all of the paternal and about two-third of the maternal pedigrees of the affected calves could be traced back to one common founder. Together with the data from experimental matings, the pedigree data support an autosomal recessive mutation being the etiology of the arachnomelia syndrome. The frequency of the mutation in the current population was estimated to be 3.32%. Conclusion We describe the repeated occurrence of the arachnomelia syndrome in Simmental calves. It resembles completely the same defect occurring in the Brown Swiss breed. The mutation became relatively widespread amongst the current population. Therefore, a control system has to be established and it is highly desirable to map the disease and develop a genetic test system.

CT and MRI imaging of the brain in MELAS syndrome.

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Pauli, Wojciech; Zarzycki, Artur; Krzyształowski, Adam; Walecka, Anna

2013-07-01

MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) is a rare, multisystem disorder which belongs to a group of mitochondrial metabolic diseases. As other diseases in this group, it is inherited in the maternal line. In this report, we discussed a case of a 10-year-old girl with clinical and radiological picture of MELAS syndrome. We would like to describe characteristic radiological features of MELAS syndrome in CT, MRI and MR spectroscopy of the brain and differential diagnosis. The rarity of this disorder and the complexity of its clinical presentation make MELAS patients among the most difficult to diagnose. Brain imaging studies require a wide differential diagnosis, primarily to distinguish between MELAS and ischemic stroke. Particularly helpful are the MRI and MR spectroscopy techniques.

CT and MRI imaging of the brain in MELAS syndrome

International Nuclear Information System (INIS)

Pauli, Wojciech; Zarzycki, Artur; Krzyształowski, Adam; Walecka, Anna

2013-01-01

MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) is a rare, multisystem disorder which belongs to a group of mitochondrial metabolic diseases. As other diseases in this group, it is inherited in the maternal line. In this report, we discussed a case of a 10-year-old girl with clinical and radiological picture of MELAS syndrome. We would like to describe characteristic radiological features of MELAS syndrome in CT, MRI and MR spectroscopy of the brain and differential diagnosis. The rarity of this disorder and the complexity of its clinical presentation make MELAS patients among the most difficult to diagnose. Brain imaging studies require a wide differential diagnosis, primarily to distinguish between MELAS and ischemic stroke. Particularly helpful are the MRI and MR spectroscopy techniques

Child Health, Maternal Marital and Socioeconomic Factors, and Maternal Health

OpenAIRE

Garbarski, Dana; Witt, Whitney P.

2012-01-01

While maternal socioeconomic status and health predict in part children’s future health and socioeconomic prospects, it is possible that the intergenerational association flows in the other direction such that child health affects maternal outcomes. Previous research demonstrates that poor child health increases the risk of adverse maternal physical and mental health outcomes. We hypothesize that poor child health may also increase the risk of poor maternal health outcomes through an interact...

The WHO maternal near-miss approach and the maternal severity index model (MSI: tools for assessing the management of severe maternal morbidity.

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Joao Paulo Souza

Full Text Available OBJECTIVES: To validate the WHO maternal near-miss criteria and develop a benchmark tool for severe maternal morbidity assessments. METHODS: In a multicenter cross-sectional study implemented in 27 referral maternity hospitals in Brazil, a one-year prospective surveillance on severe maternal morbidity and data collection was carried out. Diagnostic accuracy tests were used to assess the validity of the WHO maternal near-miss criteria. Binary logistic regression was used to model the death probability among women with severe maternal complications and benchmark the management of severe maternal morbidity. RESULTS: Of the 82,388 women having deliveries in the participating health facilities, 9,555 women presented pregnancy-related complications, including 140 maternal deaths and 770 maternal near misses. The WHO maternal near-miss criteria were found to be accurate and highly associated with maternal deaths (Positive likelihood ratio 106.8 (95% CI 99.56-114.6. The maternal severity index (MSI model was developed and found to able to describe the relationship between life-threatening conditions and mortality (Area under the ROC curve: 0.951 (95% CI 0.909-0.993. CONCLUSION: The identification of maternal near-miss cases using the WHO list of pregnancy-related life-threatening conditions was validated. The MSI model can be used as a tool for benchmarking the performance of health services managing women with severe maternal complications and provide case-mix adjustment.

Angelman syndrome in Denmark. birth incidence, genetic findings, and age at diagnosis

DEFF Research Database (Denmark)

Mertz, Line Granild Bie; Christensen, Rikke Nøhr; Vogel, Ida

2013-01-01

Angelman syndrome (AS) is a neurogenetic disorder caused by loss of expression of the maternal imprinted gene UBE3A on chromosome 15q11.2-q13. Clinical features of AS include severe intellectual disability, a happy disposition, ataxia, mandibular prognatism, and epilepsy. Our objectives were...

The maternal health outcomes of paid maternity leave: a systematic review.

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Aitken, Zoe; Garrett, Cameryn C; Hewitt, Belinda; Keogh, Louise; Hocking, Jane S; Kavanagh, Anne M

2015-04-01

Paid maternity leave has become a standard benefit in many countries throughout the world. Although maternal health has been central to the rationale for paid maternity leave, no review has specifically examined the effect of paid maternity leave on maternal health. The aim of this paper is to provide a systematic review of studies that examine the association between paid maternity leave and maternal health. We conducted a comprehensive search of electronic databases (Medline, Embase, CINAHL, PsycINFO, Web of Science, Sociological Abstracts) and Google Scholar. We searched websites of relevant organisations, reference lists of key papers and journals, and citation indices for additional studies including those not in refereed journals. There were no language restrictions. Studies were included if they compared paid maternity leave versus no paid maternity leave, or different lengths of paid leave. Data were extracted and an assessment of bias was performed independently by authors. Seven studies were identified, with participants from Australia, Sweden, Norway, USA, Canada, and Lebanon. All studies used quantitative methodologies, including cohort, cross-sectional, and repeated cross-sectional designs. Outcomes included mental health and wellbeing, general health, physical wellbeing, and intimate partner violence. The four studies that examined leave at an individual level showed evidence of maternal health benefits, whereas the three studies conducting policy-level comparisons reported either no association or evidence of a negative association. The synthesis of the results suggested that paid maternity leave provided maternal health benefits, although this varied depending on the length of leave. This has important implications for public health and social policy. However, all studies were subject to confounding bias and many to reverse causation. Given the small number of studies and the methodological limitations of the evidence, longitudinal studies are

Face Discrimination Skills in Prader-Willi Syndrome and Autism Spectrum Disorder

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Feldman, Benjamin H.; Dimitropoulos, Anastasia

2014-01-01

Individuals with Prader-Willi Syndrome (PWS) are at risk for autism spectrum disorder (ASD), including socialization problems. The PWS chromosome 15q11-13 maternal uniparental disomy (mUPD) subtype displays greater ASD symptoms than the paternal deletion (DEL) subtype. Since interpreting faces leads to successful socialization, we compared face…

Severe maternal morbidity for 2004-2005 in the three Dublin maternity hospitals.

LENUS (Irish Health Repository)

Murphy, Cliona M

2012-02-01

OBJECTIVE: To assess the prevalence and causes of severe maternal morbidity in Dublin over a two year period from 2004 to 2005. STUDY DESIGN: A prospective cohort study from January 2004 to December 2005 was undertaken in the three large maternity hospitals in Dublin, which serve a population of 1.5 million people. All are tertiary referral centres for obstetrics and neonatology and have an annual combined delivery rate of circa 23,000 births. Cases of severe maternal morbidity were identified. A systems based classification was used. The primary cause of maternal morbidity and the number of events experienced per patient was recorded. RESULTS: We identified 158 women who fulfilled the definition for severe maternal morbidity, giving a rate of 3.2 per 1000 maternities. There were two maternal deaths during the time period giving mortality to morbidity ratio of 1:79. The commonest cause of severe morbidity was vascular dysfunction related to obstetric haemorrhage. Eclampsia comprised 15.4% of cases. Intensive care or coronary care admission occurred in 12% of cases. CONCLUSION: The prevalence of severe maternal morbidity in this population is 3.2\\/1000 maternities. Obstetric haemorrhage was the main cause of severe maternal morbidity.

Mutations of the phenylalanine hydroxylase gene in patients with phenylketonuria in Shanxi, China

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Yong-An Zhou

2012-01-01

Full Text Available The variation in mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase (PAH gene was investigated in 59 children with phenylketonuria (PKU and 100 normal children. Three single nucleotide polymorphisms were detected by sequence analysis. The mutational frequencies of cDNA 696, cDNA 735 and cDNA 1155 in patients were 96.2%, 76.1% and 7.6%, respectively, whereas in healthy children the corresponding frequencies were 97.0%, 77.3% and 8.3%. In addition, 81 mutations accounted for 61.0% of the mutant alleles. R111X, H64 > TfsX9 and S70 del accounted for 5.1%, 0.8% and 0.8% mutation of alleles in exon 3, whereas EX6-96A > G accounted for 10.2% mutation of alleles in exon 6. R243Q had the highest incidence in exon 7 (12.7%, followed by Ivs7 +2T>A (5.1% and T278I (2.5%. G247V, R252Q, L255S, R261Q and E280K accounted for 0.8% while Y356X and V399V accounted for 5.9% and 5.1%, respectively, in exon 11. R413P and A434D accounted for 5.9% and 2.5%, respectively, in exon 12. Seventy-two variant alleles accounted for the 16 mutations observed here. The mutation characteristics and distributions demonstrated that EX6-96A > G and R243Q were the hot regions for mutations in the PAH gene in Shanxi patients with PKU.

Overlap of PIV syndrome, VACTERL and Pallister-Hall syndrome: clinical and molecular analysis.

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Killoran, C E; Abbott, M; McKusick, V A; Biesecker, L G

2000-07-01

The polydactyly, imperforate anus, vertebral anomalies syndrome (PIV, OMIM 174100) was determined as a distinct syndrome by Say and Gerald in 1968 (Say B, Gerald PS. Lancet 1968: 2: 688). We noted that the features of PIV overlap with the VATER association and Pallister-Hall syndrome (PHS, OMIM 146510), which includes polydactyly, (central or postaxial), shortened fingers, hypoplastic nails, renal anomalies, imperforate anus, and hypothalamic hamartoma. Truncation mutations in GL13, a zinc finger transcription factor gene, have been shown to cause PHS. We performed a molecular evaluation on a patient diagnosed with PIV, whose mother, grandfather, and maternal aunt had similar malformations. We sequenced the GLI3 gene in the patient to determine if she had a mutation. The patient was found to have a deletion in nucleotides 2188-2207 causing a frameshift mutation that predicts a truncated protein product of the gene. Later clinical studies demonstrated that the patient also has a hypothalamic hamartoma, a finding in PHS. We concluded that this family had atypical PHS and not PIV. This result has prompted us to re-evaluate the PIV literature to see if PIV is a valid entity. Based on these data and our examination of the literature, we conclude that PIV is not a valid diagnostic entity. We conclude that patients diagnosed with PIV should be reclassified as having VACTERL, or PHS, or another syndrome with overlapping malformations.

DEVELOPMENTAL FOLLOW-UP OF A FEMALE INFANT WITH RECOMBINANT DOWN SYNDROME UP TO THREE AND A HALF YEARS

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Darija Strah

2018-02-01

Full Text Available Background: Recombinant Down Syndrome with partial duplication of the long arm of chromosome 21 represents a rare form of partial trisomy 21. The cause is mostly chromosome rearrangement- pericentric inversion of maternal or paternal homologous chromosome 21 and duplication of Down syndrome critical region p11.1q22.1, resulting in a child with phenotypical signs of classical Down syndrome with psychomotorical developmental delay. Methods: We describe a Down sydrome female infant with partial trisomy of chromosome 21. Ultra- sound screening for Down syndrome in the first trimester of pregnancy determined high risk for chromosomal abnormality. Amniocentesis showed normal prenatal karyotype. After birth a female infant started to show symptoms and signs, typical for classical Down syndrome. Postnatal karyotype revealed pericentric inversion and duplication of one chro- mosome 21 of maternal origin in the p11.1q22.1 region. The follow up of female infant up to three and a half years shows signs of psychomotorical delay with no structural defects. Therefore her developmental amelioration is less expressed compared to classical Down syndrome. Conclusions: Developmental follow up of a girl with partial trisomy 21 reveals a lot of similarities with the development of children with classical trisomy 21, but less expressed: facial gestalt, short statue, hypotonia and intellectual disabilities. Global developmental delay in spite of developmental treatment grows more and more evidently.

Evidence in Latin America of recurrence of V388M, a phenylketonuria mutation with high in vitro residual activity

Energy Technology Data Exchange (ETDEWEB)

Desviat, L.R.; Perez, B.; De Lucca, M. [Universidad Autonoma de Madrid, (Spain)] [and others

1995-08-01

Phenylketonuria mutation V388M is frequent in the Iberian Peninsula. In vitro, the V388M mutant enzyme has similar immunoreactive protein and phenylalanine hydroxylase mRNA and had 43% residual activity, which correlates well with the mild phenotype exhibited by the homozygous patients. In Spain it has been detected in 5.7% of the mutant alleles and is always associated with haplotype 1.7. This mutation is also present in high frequency in some Latin American countries (Brazil, 9% Chile, 13%). It is interesting that in Chile most of the alleles bearing this mutation carry haplotype 4.3, although in Brazil it is found only on the background of haplotype 1.7. The origin of V388M in Spain on haplotype 1.7 and in Chile on haplotype 4.3 is clearly different. Recurrence is the most plausible explanation, because the mutation involves a CpG dinucleotide, and a recombination event transferring the mutation from haplotype 1 to 4 is unlikely. 29 refs., 2 figs., 3 tabs.

AN AUDIT OF THE SUDDEN-INFANT-DEATH-SYNDROME PREVENTION PROGRAM IN THE AUCKLAND REGION

NARCIS (Netherlands)

Obdeijn, M. C.; Tonkin, S.; Mitchell, E. A.

1995-01-01

Aim. An audit of the sudden infant death syndrome (SIDS) prevention programme in the Auckland region. Methods. 107 health professionals working in antenatal classes, postnatal wards, domiciliary midwifery and the Plunket Society were interviewed. Results. Maternal smoking and infant sleeping

The effects of maternal haemoglobin as an indicator of maternal ...

African Journals Online (AJOL)

Background: Maternal measles antibodies (MMA) are actively transferred through the placenta from mother to foetus. A relationship could exist between MMA of mother-infant pairs and maternal nutritional indicator (haemoglobin). Objectives: This study reviewed the effects of maternal haemoglobin (Hb) on MMA of ...

Maternal ethanol ingestion: effect on maternal and neonatal glucose balance

International Nuclear Information System (INIS)

Witek-Janusek, L.

1986-01-01

Liver glycogen availability in the newborn is of major importance for the maintenance of postnatal blood glucose levels. This study examined the effect of maternal ethanol ingestion on maternal and neonatal glucose balance in the rate. Female rats were placed on 1) the Lieber-DeCarli liquid ethanol diet, 2) an isocaloric liquid pair-diet, or 3) an ad libitum rat chow diet at 3 wk before mating and throughout gestation. Blood and livers were obtained from dams and rat pups on gestational days 21 and 22. The pups were studied up to 6 h in the fasted state and up to 24 h in the fed state. Maternal ethanol ingestion significantly decreased litter size, birth weight, and growth. A significantly higher mortality during the early postnatal period was seen in the prenatal ethanol exposed pups. Ethanol significantly decreased fed maternal liver glycogen stores but not maternal plasma glucose levels. The newborn rats from ethanol ingesting dams also had significantly decreased liver glycogen stores. Despite mobilizing their available glycogen, these prenatal ethanol exposed pups became hypoglycemic by 6 h postnatal. This was more marked in the fasted pups. Ethanol did not affect maternal nor neonatal plasma insulin levels. Thus maternal ethanol ingestion reduces maternal and neonatal liver glycogen stores and leads to postnatal hypoglycemia in the newborn rat

Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

Science.gov (United States)

Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

2015-10-13

Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.

Effects of early maternal employment on maternal health and well-being

Science.gov (United States)

Markowitz, Sara; Brooks-Gunn, Jeanne

2012-01-01

This study uses data from the National Institute of Child Health and Human Development Study on Early Child Care to examine the effects of maternal employment on maternal mental and overall health, self-reported parenting stress, and parenting quality. These outcomes are measured when children are 6 months old. Among mothers of 6-month-old infants, maternal work hours are positively associated with depressive symptoms and parenting stress and negatively associated with self-rated overall health. However, maternal employment is not associated with quality of parenting at 6 months, based on trained assessors’ observations of maternal sensitivity. PMID:23645972

Maternal sensitivity: a concept analysis.

Science.gov (United States)

Shin, Hyunjeong; Park, Young-Joo; Ryu, Hosihn; Seomun, Gyeong-Ae

2008-11-01

The aim of this paper is to report a concept analysis of maternal sensitivity. Maternal sensitivity is a broad concept encompassing a variety of interrelated affective and behavioural caregiving attributes. It is used interchangeably with the terms maternal responsiveness or maternal competency, with no consistency of use. There is a need to clarify the concept of maternal sensitivity for research and practice. A search was performed on the CINAHL and Ovid MEDLINE databases using 'maternal sensitivity', 'maternal responsiveness' and 'sensitive mothering' as key words. The searches yielded 54 records for the years 1981-2007. Rodgers' method of evolutionary concept analysis was used to analyse the material. Four critical attributes of maternal sensitivity were identified: (a) dynamic process involving maternal abilities; (b) reciprocal give-and-take with the infant; (c) contingency on the infant's behaviour and (d) quality of maternal behaviours. Maternal identity and infant's needs and cues are antecedents for these attributes. The consequences are infant's comfort, mother-infant attachment and infant development. In addition, three positive affecting factors (social support, maternal-foetal attachment and high self-esteem) and three negative affecting factors (maternal depression, maternal stress and maternal anxiety) were identified. A clear understanding of the concept of maternal sensitivity could be useful for developing ways to enhance maternal sensitivity and to maximize the developmental potential of infants. Knowledge of the attributes of maternal sensitivity identified in this concept analysis may be helpful for constructing measuring items or dimensions.

How does maternal oxytocin influence children's mental health problem and maternal mental health problem?

Science.gov (United States)

Tse, Wai S; Siu, Angela F Y; Wong, Tracy K Y

2017-12-01

This study aims to explore the interrelationship among maternal oxytocin (OT) responsiveness, maternal mental health, maternal parenting behavior, and mental health of children under a free-play interaction. 61 mother-child dyads were recruited for the study. Maternal mental health problem and parenting self-efficacy were measured using self-reported questionnaires. The mental health problems of children were also evaluated using a mother-reported questionnaire. Furthermore, salivary OT was collected before and after a standardized 10min free-play interaction. Parenting behaviors, including eye gaze and touch, were measured during the free-play interaction. Maternal OT responsiveness was significantly associated with less maternal mental health problem, touch frequency, and mental health problem of children but not with parenting self-efficacy. In the multivariate linear regression analysis that considers maternal OT responsiveness and maternal and children's mental health problems, maternal OT responsiveness was not associated with the mental health problems of children. This result suggested that maternal mental health problem played a mediational role between maternal OT responsiveness and the mental health problem of children. Results supported the assertion that maternal OT responsiveness contributed to the increased risk of maternal mental health problems and, subsequently, the risk of mental health problems of their children. Copyright © 2017 Elsevier B.V. All rights reserved.

Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation.

Directory of Open Access Journals (Sweden)

Patrik Htun

Full Text Available Since patients with phenylketonuria (PKU have to follow a lifelong restriction of natural protein to lower phenylalanine-intake, they never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6 fatty acids with the risk of early atherosclerotic changes. The aim of the study was to analyse the fatty acid profile of PKU patients and to correlate the results with surrogate markers of early atherosclerotic changes [enhanced carotid intima media thickness (CIMT and ß-stiffness index] and platelet activation.In 43 PKU patients and in 58 healthy controls we prospectively examined the fatty acid profile, CIMT, ß-stiffness index and platelet activation (flow cytometric determination of markers of platelet activation. CIMT was measured bilaterally by ultrasound. CIMTmean was defined as the mean value of the sum of CIMTleft and CIMTright.Despite of lower HDL-cholesterol and higher triglyceride concentrations in the PKU group, there was no significant difference in the omega-6 or omega-3 fatty acid profile, CIMT, ß-stiffness index between both groups. Platelet activation was not enhanced in the PKU group.Fish-free diet does not induce early atherosclerotic changes or enhanced platelet activation in PKU patients.

Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation.

Science.gov (United States)

Htun, Patrik; Nee, Jens; Ploeckinger, Ursula; Eder, Klaus; Geisler, Tobias; Gawaz, Meinrad; Bocksch, Wolfgang; Fateh-Moghadam, Suzanne

2015-01-01

Since patients with phenylketonuria (PKU) have to follow a lifelong restriction of natural protein to lower phenylalanine-intake, they never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6 fatty acids with the risk of early atherosclerotic changes. The aim of the study was to analyse the fatty acid profile of PKU patients and to correlate the results with surrogate markers of early atherosclerotic changes [enhanced carotid intima media thickness (CIMT) and ß-stiffness index] and platelet activation. In 43 PKU patients and in 58 healthy controls we prospectively examined the fatty acid profile, CIMT, ß-stiffness index and platelet activation (flow cytometric determination of markers of platelet activation). CIMT was measured bilaterally by ultrasound. CIMTmean was defined as the mean value of the sum of CIMTleft and CIMTright. Despite of lower HDL-cholesterol and higher triglyceride concentrations in the PKU group, there was no significant difference in the omega-6 or omega-3 fatty acid profile, CIMT, ß-stiffness index between both groups. Platelet activation was not enhanced in the PKU group. Fish-free diet does not induce early atherosclerotic changes or enhanced platelet activation in PKU patients.

Food Products Made With Glycomacropeptide, a Low Phenylalanine Whey Protein, Provide a New Alternative to Amino Acid-Based Medical Foods for Nutrition Management of Phenylketonuria

Science.gov (United States)

Van Calcar, Sandra C.; Ney, Denise M.

2012-01-01

Phenylketonuria (PKU), an inborn error in phenylalanine (phe) metabolism, requires lifelong nutrition management with a low-phe diet, which includes a phe-free amino acid-based medical formula to provide the majority of an individual’s protein needs. Compliance with this diet is often difficult for older children, adolescents and adults with PKU. The whey protein glycomacropeptide (GMP) is ideally suited for the PKU diet since it is naturally low in phe. Nutritionally complete, acceptable medical foods and beverages can be made with GMP to increase the variety of protein sources for the PKU diet. As an intact protein, GMP improves protein utilization and increases satiety compared with amino acids. Thus, GMP provides a new, more physiologic source of low-phe dietary protein for those with PKU. PMID:22818728

Evaluation of Neuropsychiatric Function in Phenylketonuria: Psychometric Properties of the ADHD Rating Scale-IV and Adult ADHD Self-Report Scale Inattention Subscale in Phenylketonuria.

Science.gov (United States)

Wyrwich, Kathleen W; Auguste, Priscilla; Yu, Ren; Zhang, Charlie; Dewees, Benjamin; Winslow, Barbara; Yu, Shui; Merilainen, Markus; Prasad, Suyash

2015-06-01

Previous qualitative research among adults and parents of children with phenylketonuria (PKU) has identified inattention as an important psychiatric aspect of this condition. The parent-reported ADHD Rating Scale-IV (ADHD RS-IV) and the Adult ADHD Self-Report Scale (ASRS) have been validated for measuring inattention symptoms in persons with attention-deficit/hyperactivity disorder (ADHD); however, their psychometric attributes for measuring PKU-related inattention have not been established. The primary objective of this investigation was to demonstrate the reliability, validity, and responsiveness of the ADHD RS-IV and ASRS inattention symptoms subscales in a randomized controlled trial of patients with PKU aged 8 years or older. A post hoc analysis investigated the psychometric properties (Rasch model fit, reliability, construct validity, and responsiveness) of the ADHD RS-IV and ASRS inattention subscales using data from a phase 3b, double-blind, placebo-controlled clinical trial in those with PKU aged 8 years or older. The Rasch results revealed good model fit, and reliability analyses revealed strong internal consistency reliability (α ≥ 0.87) and reproducibility (intraclass correlation coefficient ≥ 0.87) for both measures. Both inattention measures demonstrated the ability to discriminate between known groups (P < 0.001) created by the Clinical Global Impression-Severity scale. Correlations between the ADHD RS-IV and the ASRS with the Clinical Global Impression-Severity scale and the age-appropriate Behavior Rating Inventory of Executive Function Working Memory subscale were consistently moderate to strong (r ≥ 0.56). Similarly, results of the change score correlations were of moderate magnitude (r ≥ 0.43) for both measures when compared with changes over time in Behavior Rating Inventory of Executive Function Working Memory subscales. These findings of reliability, validity, and responsiveness of both the ADHD RS-IV and the ASRS inattention scales

Maternal Mortality in Texas.

Science.gov (United States)

Baeva, Sonia; Archer, Natalie P; Ruggiero, Karen; Hall, Manda; Stagg, Julie; Interis, Evelyn Coronado; Vega, Rachelle; Delgado, Evelyn; Hellerstedt, John; Hankins, Gary; Hollier, Lisa M

2017-05-01

A commentary on maternal mortality in Texas is provided in response to a 2016 article in Obstetrics & Gynecology by MacDorman et al. While the Texas Department of State Health Services and the Texas Maternal Mortality and Morbidity Task Force agree that maternal mortality increased sharply from 2010 to 2011, the percentage change or the magnitude of the increase in the maternal mortality rate in Texas differs depending on the statistical methods used to compute and display it. Methodologic challenges in identifying maternal death are also discussed, as well as risk factors and causes of maternal death in Texas. Finally, several state efforts currently underway to address maternal mortality in Texas are described. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The effects of dietary and lifestyle interventions among pregnant women who are overweight or obese on longer-term maternal and early childhood outcomes

DEFF Research Database (Denmark)

Dodd, Jodie M.; Grivell, Rosalie M.; Louise, Jennie

2017-01-01

Background: The aim of this individual participant data meta-analysis (IPDMA) is to evaluate the effects of dietary and lifestyle interventions among pregnant women who are overweight or obese on later maternal and early childhood outcomes at ages 3-5 years. Methods/design: We will build...... or is being undertaken. The primary maternal outcome is a diagnosis of maternal metabolic syndrome. The primary childhood outcome is BMI above 90%. We have identified 7 relevant trials, involving 5425 women who were overweight or obese during pregnancy, with approximately 3544 women and children with follow......-up assessments available for inclusion in the meta-analysis. Discussion: The proposed IPDMA provides an opportunity to evaluate the effect of dietary and lifestyle interventions among pregnant women who are overweight or obese on later maternal and early childhood health outcomes, including risk of obesity...

The phenotypic spectrum of Schaaf-Yang syndrome : 18 new affected individuals from 14 families

NARCIS (Netherlands)

Fountain, Michael D.; Aten, Emmelien; Cho, Megan T.; Juusola, Jane; Walkiewicz, Magdalena A.; Ray, Joseph W.; Xia, Fan; Yang, Yaping; Graham, Brett H.; Bacino, Carlos A.; Potocki, Lorraine; van Haeringen, Arie; Ruivenkamp, Claudia A. L.; Mancias, Pedro; Northrup, Hope; Kukolich, Mary K.; Weiss, Marjan M.; van Ravenswaaij-Arts, Conny M. A.; Mathijssen, Inge B.; Levesque, Sebastien; Meeks, Naomi; Rosenfeld, Jill A.; Lemke, Danielle; Hamosh, Ada; Lewis, Suzanne K.; Race, Simone; Stewart, Laura L.; Hay, Beverly; Lewis, Andrea M.; Guerreiro, Rita L.; Bras, Jose T.; Martins, Marcia P.; Derksen-Lubsen, Gerarda; Peeters, Els; Stumpel, Connie; Stegmann, Sander; Bok, Levinus A.; Santen, Gijs W. E.; Schaaf, Christian P.

Purpose: Truncating mutations in the maternally imprinted, paternally expressed gene MAGEL2, which is located in the Prader-Willi critical region 15q11-13, have recently been reported to cause Schaaf -Yang syndrome, a Prader-Willi-like disease that manifests as developmental delay/intellectual

Mitochondria: role of citrulline and arginine supplementation in MELAS syndrome.

Science.gov (United States)

El-Hattab, Ayman W; Emrick, Lisa T; Chanprasert, Sirisak; Craigen, William J; Scaglia, Fernando

2014-03-01

Mitochondria are found in all nucleated human cells and generate most of the cellular energy. Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient ATP to meet the energy needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a frequent maternally inherited mitochondrial disorder. There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS syndrome and results in impaired blood perfusion that contributes significantly to several complications including stroke-like episodes, myopathy, and lactic acidosis. Both arginine and citrulline act as NO precursors and their administration results in increased NO production and hence can potentially have therapeutic utility in MELAS syndrome. Citrulline raises NO production to a greater extent than arginine, therefore, citrulline may have a better therapeutic effect. Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS syndrome are needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Maternal-fetal cholesterol transport in the second half of mouse pregnancy does not involve LDL receptor-related protein 2.

Science.gov (United States)

Zwier, M V; Baardman, M E; van Dijk, T H; Jurdzinski, A; Wisse, L J; Bloks, V W; Berger, R M F; DeRuiter, M C; Groen, A K; Plösch, T

2017-08-01

LDL receptor-related protein type 2 (LRP2) is highly expressed on both yolk sac and placenta. Mutations in the corresponding gene are associated with severe birth defects in humans, known as Donnai-Barrow syndrome. We here characterized the contribution of LRP2 and maternal plasma cholesterol availability to maternal-fetal cholesterol transport and fetal cholesterol levels in utero in mice. Lrp2 +/- mice were mated heterozygously to yield fetuses of all three genotypes. Half of the dams received a 0.5% probucol-enriched diet during gestation to decrease maternal HDL cholesterol. At E13.5, the dams received an injection of D7-labelled cholesterol and were provided with 1- 13 C acetate-supplemented drinking water. At E16.5, fetal tissues were collected and maternal cholesterol transport and fetal synthesis quantified by isotope enrichments in fetal tissues by GC-MS. The Lrp2 genotype did not influence maternal-fetal cholesterol transport and fetal cholesterol. However, lowering of maternal plasma cholesterol levels by probucol significantly reduced maternal-fetal cholesterol transport. In the fetal liver, this was associated with increased cholesterol synthesis rates. No indications were found for an interaction between the Lrp2 genotype and maternal probucol treatment. Maternal-fetal cholesterol transport and endogenous fetal cholesterol synthesis depend on maternal cholesterol concentrations but do not involve LRP2 in the second half of murine pregnancy. Our results suggest that the mouse fetus can compensate for decreased maternal cholesterol levels. It remains a relevant question how the delicate system of cholesterol transport and synthesis is regulated in the human fetus and placenta. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Rural maternity care.

Science.gov (United States)

Miller, Katherine J; Couchie, Carol; Ehman, William; Graves, Lisa; Grzybowski, Stefan; Medves, Jennifer

2012-10-01

To provide an overview of current information on issues in maternity care relevant to rural populations. Medline was searched for articles published in English from 1995 to 2012 about rural maternity care. Relevant publications and position papers from appropriate organizations were also reviewed. This information will help obstetrical care providers in rural areas to continue providing quality care for women in their communities. Recommendations 1. Women who reside in rural and remote communities in Canada should receive high-quality maternity care as close to home as possible. 2. The provision of rural maternity care must be collaborative, woman- and family-centred, culturally sensitive, and respectful. 3. Rural maternity care services should be supported through active policies aligned with these recommendations. 4. While local access to surgical and anaesthetic services is desirable, there is evidence that good outcomes can be sustained within an integrated perinatal care system without local access to operative delivery. There is evidence that the outcomes are better when women do not have to travel far from their communities. Access to an integrated perinatal care system should be provided for all women. 5. The social and emotional needs of rural women must be considered in service planning. Women who are required to leave their communities to give birth should be supported both financially and emotionally. 6. Innovative interprofessional models should be implemented as part of the solution for high-quality, collaborative, and integrated care for rural and remote women. 7. Registered nurses are essential to the provision of high-quality rural maternity care throughout pregnancy, birth, and the postpartum period. Maternity nursing skills should be recognized as a fundamental part of generalist rural nursing skills. 8. Remuneration for maternity care providers should reflect the unique challenges and increased professional responsibility faced by providers in

Maternal adiposity and maternal and cord blood concentrations of vitamin D [25(OHD3

Directory of Open Access Journals (Sweden)

Fernanda F.A. Simões

2016-10-01

Full Text Available Obesity is associated with lower concentrations of vitamin D [25(OHD3] in children, adolescents and adults, but it remains unclear whether maternal adiposity influences maternal and foetal concentrations of this vitamin. The objective of this cross-sectional study was to assess the relationship between maternal adiposity and maternal and cord blood concentrations of vitamin D. It involved 101 mother–newborn pairs from a public maternity in Sao Paulo city, Brazil. Demographic, socioeconomic and obstetric data, as well as anthropometry, physical activity and vitamin D supplementation during pregnancy, were investigated. Maternal adiposity was assessed by bioelectrical impedance. Maternal and cord blood concentrations of vitamin D were measured by high-performance liquid chromatography. Two multiple linear regression models that included maternal and cord blood vitamin D concentrations as outcomes and maternal adiposity as independent variable were used. No association was observed between maternal adiposity and maternal or cord blood concentrations of vitamin D. Maternal vitamin D concentration was associated with race, physical activity and vitamin D supplementation (adj. R2 = 0.74. Cord blood vitamin D concentration was associated with maternal vitamin D concentration (adj. R2 = 0.24. Although fat mass quantification is important to understand vitamin D status during all stages of life, this may not be true in pregnancy as race, vitamin D supplementation and physical activity appeared to be more relevant to vitamin D status. Understanding vitamin D metabolism in pregnancy may elucidate how or if adiposity influences maternal vitamin D status and how it impacts vitamin D transport to the foetus.

Maternal Emotional Availability and Its Association with Maternal Psychopathology, Attachment Style Insecurity and Theory of Mind.

Science.gov (United States)

Licata, Maria; Zietlow, Anna-Lena; Träuble, Birgit; Sodian, Beate; Reck, Corinna

High maternal emotional availability (EA) positively affects various domains of child development. However, the question of which factors promote or hinder maternal EA has not been investigated systematically. The present study investigated several maternal characteristics, namely maternal psychopathology, maternal attachment style insecurity, and theory of mind (ToM) as possible factors that influence maternal EA. The sample was comprised of 56 mothers and their preschool-aged children. Half of the mothers were diagnosed with postpartum depression and or anxiety disorders according to DSM-IV, and the other half were healthy controls. The results showed that both low maternal attachment style insecurity and high ToM skills significantly predicted maternal EA sensitivity, independently from maternal postpartum and concurrent psychopathology and education. Moreover, maternal attachment style insecurity fully mediated the link between maternal postpartum psychopathology and sensitivity. The findings suggest that maternal attachment style security can buffer negative effects of maternal psychopathology on maternal sensitivity in the mother-child interaction. © 2016 S. Karger AG, Basel.

The placental problem: Linking abnormal cytotrophoblast differentiation to the maternal symptoms of preeclampsia

Directory of Open Access Journals (Sweden)

Fisher Susan J

2004-07-01

Full Text Available Abstract The placenta is a remarkable organ. In normal pregnancy its specialized cells (termed cytotrophoblasts differentiate into various specialized subpopulations that play pivotal roles in governing fetal growth and development. One cytotrophoblast subset acquires tumor-like properties that allow the cells to invade the decidua and myometrium, a process that attaches the placenta to the uterus. The same subset also adopts a vascular phenotype that allows these fetal cells to breach and subsequently line uterine blood vessels, a process that channels maternal blood to the rest of the placenta. In the pregnancy complication preeclampsia, which is characterized by the sudden onset of maternal hypertension, proteinuria and edema, cytotrophoblast invasion is shallow and vascular transformation incomplete. These findings, together with very recent evidence from animal models, suggest that preeclampsia is associated with abnormal placental production of vasculogenic/angiogenic substances that reach the maternal circulation with the potential to produce at least a subset of the clinical signs of this syndrome. The current challenge is to build on this knowledge to design clinically useful tests for predicting, diagnosing and treating this dangerous disorder.

High dose sapropterin dihydrochloride therapy improves monoamine neurotransmitter turnover in murine phenylketonuria (PKU).

Science.gov (United States)

Winn, Shelley R; Scherer, Tanja; Thöny, Beat; Harding, Cary O

2016-01-01

Central nervous system (CNS) deficiencies of the monoamine neurotransmitters, dopamine and serotonin, have been implicated in the pathophysiology of neuropsychiatric dysfunction in phenylketonuria (PKU). Increased brain phenylalanine concentration likely competitively inhibits the activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the rate limiting steps in dopamine and serotonin synthesis respectively. Tetrahydrobiopterin (BH4) is a required cofactor for TH and TPH activity. Our hypothesis was that treatment of hyperphenylalaninemic Pah(enu2/enu2) mice, a model of human PKU, with sapropterin dihydrochloride, a synthetic form of BH4, would stimulate TH and TPH activities leading to improved dopamine and serotonin synthesis despite persistently elevated brain phenylalanine. Sapropterin (20, 40, or 100mg/kg body weight in 1% ascorbic acid) was administered daily for 4 days by oral gavage to Pah(enu2/enu2) mice followed by measurement of brain biopterin, phenylalanine, tyrosine, tryptophan and monoamine neurotransmitter content. A significant increase in brain biopterin content was detected only in mice that had received the highest sapropterin dose, 100mg/kg. Blood and brain phenylalanine concentrations were unchanged by sapropterin therapy. Sapropterin therapy also did not alter the absolute amounts of dopamine and serotonin in brain but was associated with increased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), dopamine and serotonin metabolites respectively, in both wild type and Pah(enu2/enu2) mice. Oral sapropterin therapy likely does not directly affect central nervous system monoamine synthesis in either wild type or hyperphenylalaninemic mice but may stimulate synaptic neurotransmitter release and subsequent metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

Congenital heart disease and its journey from dental plaque to arterial plaque

Directory of Open Access Journals (Sweden)

Vinathi Reddy Kankara

2016-01-01

Full Text Available Congenital heart disease is mostly found in children, approximately around 7–10% from overall heart diseases. The etiology is multifactorial but reported associations include untreated maternal diabetes, phenylketonuria, intake of retinoic acid last but not least is oral pathogens present in periodontopathic bacteria. The main objective of this article is to explain about different mechanisms by which it is associated with dental, periodontal manifestations. It also explains about two patients who reported to our hospital with congenital heart disease and their dental and periodontal management.

[Time perception, maternal tasks, and maternal role behavior among pregnant Japanese women].

Science.gov (United States)

Yamamoto, A

1996-01-01

The relationship of time perception, maternal tasks, and maternal role behavior was examined in 140 pregnant Japanese women with a short-term longitudinal design. A model developed by Rubin provided the conceptual framework for this research. The Time Perception Scale. Time Production Method, and the Prefatory Maternal Response measured the study variables. Study results revealed significant differences in duration of time, time production, maternal-fetal attachment, and maternal role behavior before and after quickening(fetal movement)occurred. Medium to strong positive relationships among time orientation, maternal-fetal attachment, gratification, and maternal role behavior were found before and after movement. After quickening, a weak relationship between time orientation and duration was found. After controlling maternal-fetal attachment and gratification in pregnancy and maternal role, orientation in time perception accounted for significant amounts of variance in maternal role behavior before and after fetal movement. Results show that the process of becoming a mother, which started before quickening, increased in magnitude after fetal movement. The function of fetal movement is important in developing motherhood. In the process of becoming a mother, cognitive, emotional, and behavioral aspects in becoming a mother are inseparable from each other. Future orientation of time perception contributes to development of maternal role behavior. Having a future orientation during pregnancy may indicate hope or positive expectation. Based on these findings, several recommendations were proposed: (a)to study further the general process of becoming a mother and the role of time perception in developing motherhood, (b)to disseminate information to the general public about the process in development of motherhood, (c)to construct theory to explain the process of becoming a mother, and(d)to conduct future research to clarify the construct of time perception and attachment.

Mutation frequency and genotype/phenotype correlation among phenylketonuria patients from Georgia

Energy Technology Data Exchange (ETDEWEB)

Woo, S.L.C.; Martinez, D.; Kuozmine, A. [Baylor College of Medicine, Houston, TX (United States)] [and others

1994-09-01

Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). To determine the molecular basis of PKU in the state of Georgia, thirty-five Georgian PKU patients representing sixty independent alleles were examined by a combination of DGGE and direct sequence analysis. At present, this approach has led to the identification of 55/60 or about 92% of all mutant alleles. The relatively high frequencies of mutations common to the British Isles (R408W, I65T and L348V) are compatible with 1990 census data showing that 34% of the general Georgian population claim Irish, English or Scottish ancestors. Three new mutations, E76A (1/60), R241L (2/60), and R400R (2/60), were also detected in this study. Although the nucleotide substitution in codon 400 (AGG{r_arrow}CGG) did not change the amino acid sequence, it was the only base change detected in a scan of all 13 exons of two independent alleles. Since codon 400 is split between exons 11 and 12, this change may exert some effect on splicing, as has previously been seen in the PAH gene for the silent mutation Q304Q and the nonsense mutation Y356X, each of which effect codons immediately adjacent to splicing signals. This hypothesis remains to be tested by expression analysis or studies of ectopic transcripts. The remaining 19 characterized alleles contained one of 15 previously identified mutations. Twenty-five of the thirty non-related patients examined in this study were completely genotyped, and there was a strong correlation between mutant PAH genotype, PAH activity predicted from in vitro expression studies where known, and PKU or HPA phenotype. For mutations not yet studied by expression analysis, this correlation suggests that L213P, R241L, Y277D may drastically reduce residual PAH activity while F39L and E76A may retain significant amounts of PAH activity.

Communicative and psycholinguistic abilities in children with phenylketonuria and congenital hypothyroidism

Science.gov (United States)

GEJÃO, Mariana Germano; FERREIRA, Amanda Tragueta; SILVA, Greyce Kelly; ANASTÁCIO-PESSAN, Fernanda da Luz; LAMÔNICA, Dionísia Aparecida Cusin

2009-01-01

ABSTRACT The Neonatal Screening for Inborn Errors of Metabolism of the Association of Parents and Friends of Special Needs Individuals (APAE) - Bauru, Brazil, was implanted and accredited by the Brazilian Ministry of Health in 1998. It covers about 286 cities of the Bauru region and 420 collection spots. Their activities include screening, diagnosis, treatment and assistance to congenital hypothyroidism (CH) and phenylketonuria (PKU), among others. In 2005, a partnership was established with the Department of Speech-Language Pathology and Audiology, Bauru School of Dentistry, University of São Paulo, Bauru, seeking to characterize and to follow, by means of research studies, the development of the communicative abilities of children with CH and PKU. Objective: The aim of this study was to describe communicative and psycholinguistic abilities in children with CH and PKU. Materials and Methods: Sixty-eight children (25 children aged 1 to 120 months with PKU and 43 children aged 1 to 60 months with CH) participated in the study. The handbooks were analyzed and different instruments were applied (Observation of Communication Behavior, Early Language Milestone Scale, Peabody Picture Vocabulary Test, Gesell & Amatruda's Behavioral Development Scale, Portage Operation Inventory, Language Development Evaluation Scale, Denver Developmental Screening Test, ABFW Child Language Test-phonology and Illinois Test of Psycholinguistic Abilities), according to the children's age group and developmental level. Results: It was observed that the children with PKU and CH at risk for alterations in their developmental abilities (motor, cognitive, linguistic, adaptive and personal-social), mainly in the first years of life. Alterations in the psycholinguistic abilities were also found, mainly after the preschool age. Attention deficits, language and cognitive alterations were more often observed in children with CH, while attention deficits with hyperactivity and alterations in the

Communicative and psycholinguistic abilities in children with phenylketonuria and congenital hypothyroidism

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Mariana Germano Gejão

2009-01-01

Full Text Available The Neonatal Screening for Inborn Errors of Metabolism of the Association of Parents and Friends of Special Needs Individuals (APAE - Bauru, Brazil, was implanted and accredited by the Brazilian Ministry of Health in 1998. It covers about 286 cities of the Bauru region and 420 collection spots. Their activities include screening, diagnosis, treatment and assistance to congenital hypothyroidism (CH and phenylketonuria (PKU, among others. In 2005, a partnership was established with the Department of Speech-Language Pathology and Audiology, Bauru School of Dentistry, University of São Paulo, Bauru, seeking to characterize and to follow, by means of research studies, the development of the communicative abilities of children with CH and PKU. OBJECTIVE: The aim of this study was to describe communicative and psycholinguistic abilities in children with CH and PKU. MATERIALS AND METHODS: Sixty-eight children (25 children aged 1 to 120 months with PKU and 43 children aged 1 to 60 months with CH participated in the study. The handbooks were analyzed and different instruments were applied (Observation of Communication Behavior, Early Language Milestone Scale, Peabody Picture Vocabulary Test, Gesell & Amatruda's Behavioral Development Scale, Portage Operation Inventory, Language Development Evaluation Scale, Denver Developmental Screening Test, ABFW Child Language Test-phonology and Illinois Test of Psycholinguistic Abilities, according to the children's age group and developmental level. RESULTS: It was observed that the children with PKU and CH at risk for alterations in their developmental abilities (motor, cognitive, linguistic, adaptive and personal-social, mainly in the first years of life. Alterations in the psycholinguistic abilities were also found, mainly after the preschool age. Attention deficits, language and cognitive alterations were more often observed in children with CH, while attention deficits with hyperactivity and alterations in the

Guidelineness of the parameters using integrated test in down syndrome risk prediction

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Lee, Jin Won; Go, Sung Jin; Kang, Se Sik; Kim, Chang Soo

2016-01-01

This study was an evaluation of the significance of each parameter through aimed at pregnant women subjected to screening test(integrated test) in predicting risk of Down syndrome. We retrospectively analysed the correlation of risk of Down's syndrome with Nuchal Translucency(NT) images measured by ultrasound, Pregnancy Associated Plasma Protein A(PAPP-A), alpha-fetoprotein(AFP), unconjugated estriol(uE3), human chorionic gonadotrophin(hCG) and Inhibin A by maternal serum. As a result, a significant correlation with NT, uE3, hCG, Inhibin A is revealed with Down's syndrome risk(P<.001). In ROC analysis, AUC of Inhibin A is analysed as the biggest predictor of Down's syndrome(0.859). And the criterion for cut-off was inhibin A 1.4 MoM(sensitivity 81.8%, specificity 75.9%). In conclusion, Inhibin A was the most useful in parameters to predict Down's syndrome in the integrated test. If we make up for the weakness based on the cut-off value of parameters they will be able to be used as an independent indicator in the risk of Down's syndrome screening

Are species differences in maternal effects arising from maternal care adaptive?

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Benowitz, K M; Moody, K J; Moore, A J

2015-02-01

Parental care benefits offspring through maternal effects influencing their development, growth and survival. However, although parental care in general is likely the result of adaptive evolution, it does not follow that specific differences in the maternal effects that arise from care are also adaptive. Here, we used an interspecific cross-fostering design in the burying beetle species Nicrophorus orbicollis and N. vespilloides, both of which have elaborate parental care involving direct feeding of regurgitated food to offspring, to test whether maternal effects are optimized within a species and therefore adaptive. Using a full-factorial design, we first demonstrated that N. orbicollis care for offspring longer regardless of recipient species. We then examined offspring development and mass in offspring reared by hetero- or conspecific parents. As expected, there were species-specific direct effects independent of the maternal effects, as N. orbicollis larvae were larger and took longer to develop than N. vespilloides regardless of caregiver. We also found significant differences in maternal effects: N. vespilloides maternal care caused more rapid development of offspring of either species. Contrary to expectations if maternal effects were species-specific, there were no significant interactions between caretaker and recipient species for either development time or mass, suggesting that these maternal effects are general rather than optimized within species. We suggest that rather than coadaptation between parents and offspring performance, the species differences in maternal effects may be correlated with direct effects, and that their evolution is driven by selection on those direct effects. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Maternal Depression, Maternal Expressed Emotion, and Youth Psychopathology

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Tompson, Martha C.; Pierre, Claudette B.; Boger, Kathryn Dingman; McKowen, James W.; Chan, Priscilla T.; Freed, Rachel D.

2010-01-01

Across development, maternal depression has been found to be a risk factor for youth psychopathology generally and youth depression specifically. Maternal Expressed Emotion (EE) has been examined as a predictor of outcome among youth with depression. The present study explored the associations between youth psychopathology and two…

Altered serotonin, dopamine and norepinepherine levels in 15q duplication and Angelman syndrome mouse models.

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M Febin Farook

Full Text Available Childhood neurodevelopmental disorders like Angelman syndrome and autism may be the result of underlying defects in neuronal plasticity and ongoing problems with synaptic signaling. Some of these defects may be due to abnormal monoamine levels in different regions of the brain. Ube3a, a gene that causes Angelman syndrome (AS when maternally deleted and is associated with autism when maternally duplicated has recently been shown to regulate monoamine synthesis in the Drosophila brain. Therefore, we examined monoamine levels in striatum, ventral midbrain, frontal cerebral cortex, cerebellar cortex and hippocampus in Ube3a deficient and Ube3a duplication animals. We found that serotonin (5HT, a monoamine affected in autism, was elevated in the striatum and cortex of AS mice. Dopamine levels were almost uniformly elevated compared to control littermates in the striatum, midbrain and frontal cortex regardless of genotype in Ube3a deficient and Ube3a duplication animals. In the duplication 15q autism mouse model, paternal but not maternal duplication animals showed a decrease in 5HT levels when compared to their wild type littermates, in accordance with previously published data. However, maternal duplication animals show no significant changes in 5HT levels throughout the brain. These abnormal monoamine levels could be responsible for many of the behavioral abnormalities observed in both AS and autism, but further investigation is required to determine if any of these changes are purely dependent on Ube3a levels in the brain.

Accurate molecular diagnosis of phenylketonuria and tetrahydrobiopterin-deficient hyperphenylalaninemias using high-throughput targeted sequencing

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Trujillano, Daniel; Perez, Belén; González, Justo; Tornador, Cristian; Navarrete, Rosa; Escaramis, Georgia; Ossowski, Stephan; Armengol, Lluís; Cornejo, Verónica; Desviat, Lourdes R; Ugarte, Magdalena; Estivill, Xavier

2014-01-01

Genetic diagnostics of phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficient hyperphenylalaninemia (BH4DH) rely on methods that scan for known mutations or on laborious molecular tools that use Sanger sequencing. We have implemented a novel and much more efficient strategy based on high-throughput multiplex-targeted resequencing of four genes (PAH, GCH1, PTS, and QDPR) that, when affected by loss-of-function mutations, cause PKU and BH4DH. We have validated this approach in a cohort of 95 samples with the previously known PAH, GCH1, PTS, and QDPR mutations and one control sample. Pooled barcoded DNA libraries were enriched using a custom NimbleGen SeqCap EZ Choice array and sequenced using a HiSeq2000 sequencer. The combination of several robust bioinformatics tools allowed us to detect all known pathogenic mutations (point mutations, short insertions/deletions, and large genomic rearrangements) in the 95 samples, without detecting spurious calls in these genes in the control sample. We then used the same capture assay in a discovery cohort of 11 uncharacterized HPA patients using a MiSeq sequencer. In addition, we report the precise characterization of the breakpoints of four genomic rearrangements in PAH, including a novel deletion of 899 bp in intron 3. Our study is a proof-of-principle that high-throughput-targeted resequencing is ready to substitute classical molecular methods to perform differential genetic diagnosis of hyperphenylalaninemias, allowing the establishment of specifically tailored treatments a few days after birth. PMID:23942198

Association between Maternal Smoking during Pregnancy and Low Birthweight: Effects by Maternal Age.

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Wei Zheng

Full Text Available Maternal smoking during pregnancy has been consistently related to low birthweight. However, older mothers, who are already at risk of giving birth to low birthweight infants, might be even more susceptible to the effects of maternal smoking. Therefore, this study aimed to examine the modified association between maternal smoking and low birthweight by maternal age.Data were obtained from a questionnaire survey of all mothers of children born between 2004 and 2010 in Okinawa, Japan who underwent medical check-ups at age 3 months. Variables assessed were maternal smoking during pregnancy, maternal age, gestational age, parity, birth year, and complications during pregnancy. Stratified analyses were performed using a logistic regression model.In total, 92641 participants provided complete information on all variables. Over the 7 years studied, the proportion of mothers smoking during pregnancy decreased from 10.6% to 5.0%, while the prevalence of low birthweight did not change remarkably (around 10%. Maternal smoking was significantly associated with low birthweight in all age groups. The strength of the association increased with maternal age, both in crude and adjusted models.Consistent with previous studies conducted in Western countries, this study demonstrates that maternal age has a modifying effect on the association between maternal smoking and birthweight. This finding suggests that specific education and health care programs for older smoking mothers are important to improve their foetal growth.

Motor development skills of 1- to 4-year-old Iranian children with early treated phenylketonuria.

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Nazi, Sepideh; Rohani, Farzaneh; Sajedi, Firoozeh; Biglarian, Akbar; Setoodeh, Arya

2014-01-01

Objective : To gauge the gross and fine motor development of early treated phenylketonuria (ETPKU) in children in the age range of 1-4 years. Methods : A cross-sectional analytic study was conducted in PKU clinics (reference clinics for PKU follow-up), Tehran, Iran. Seventy children with ETPKU were selected as the case group for the study. ETPKU children were those with early and continuous treatment with a phenylalanine-restricted diet (the mean of blood phenylalanine level during the recent 6 months was 2-6 mg/dL or 120-360 μmol/L). Also, 100 healthy and normal children matched with the ETPKU group for age were randomly selected from 4 kindergartens in four parts of Tehran as a control group. The measurements consisted of a demographic questionnaire, Peabody Developmental Motor Scale-2 (PDMS-2), and pediatrician assessment. Motor quotients were determined by PDMS-2 and then compared in both groups by two independent samples t-test. Results : The mean ages in case and control group were 28.5 (± 11.6) and 29.7 (± 11.3) months, respectively. Comparison of the mean fine, gross, and total developmental motor quotients (DMQs) showed statistically significant differences between the two groups (p fine and total DMQs of ETPKU children were also correlated with age. In addition, there was a negative correlation between the phenylalanine level and fine (p motor development. It is recommended to plan programs for early detection and intervention of developmental delays in these children.

Mutation Analysis in Classical Phenylketonuria Patients Followed by Detecting Haplotypes Linked to Some PAH Mutations.

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Dehghanian, Fatemeh; Silawi, Mohammad; Tabei, Seyed M B

2017-02-01

Deficiency of phenylalanine hydroxylase (PAH) enzyme and elevation of phenylalanine in body fluids cause phenylketonuria (PKU). The gold standard for confirming PKU and PAH deficiency is detecting causal mutations by direct sequencing of the coding exons and splicing involved sequences of the PAH gene. Furthermore, haplotype analysis could be considered as an auxiliary approach for detecting PKU causative mutations before direct sequencing of the PAH gene by making comparisons between prior detected mutation linked-haplotypes and new PKU case haplotypes with undetermined mutations. In this study, 13 unrelated classical PKU patients took part in the study detecting causative mutations. Mutations were identified by polymerase chain reaction (PCR) and direct sequencing in all patients. After that, haplotype analysis was performed by studying VNTR and PAHSTR markers (linked genetic markers of the PAH gene) through application of PCR and capillary electrophoresis (CE). Mutation analysis was performed successfully and the detected mutations were as follows: c.782G>A, c.754C>T, c.842C>G, c.113-115delTCT, c.688G>A, and c.696A>G. Additionally, PAHSTR/VNTR haplotypes were detected to discover haplotypes linked to each mutation. Mutation detection is the best approach for confirming PAH enzyme deficiency in PKU patients. Due to the relatively large size of the PAH gene and high cost of the direct sequencing in developing countries, haplotype analysis could be used before DNA sequencing and mutation detection for a faster and cheaper way via identifying probable mutated exons.

Maternal and neonatal outcomes of respiratory failure during pregnancy

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Chen-Yiu Hung

2018-05-01

Full Text Available Background: Obstetric patients comprise a limited portion of intensive care unit patients, but they often present with unfamiliar conditions and exhibit the potential for catastrophic deterioration. This study evaluated the maternal and neonatal outcomes of respiratory failure during pregnancy. Methods: Information on 71 patients at >25 weeks gestation in the ICU with respiratory failure was recorded between 2009 and 2013. The characteristics and outcomes of mothers and fetuses were determined through a retrospective chart review and evaluated using Student's t test, chi-square test, and Fisher's exact test. Results: The leading causes of respiratory failure were postpartum hemorrhage and severe preeclampsia in the obstetric causes group and pneumonia in the nonobstetric causes group during pregnancy and the peripartum period. The non-obstetric causes group exhibited a higher incidence of acute respiratory distress syndrome and renal replacement therapy as well as requiring more ventilator days. The patients in the obstetric causes group showed significant improvement after delivery in the partial pressure of arterial oxygen to the fraction of inspired oxygen and peak inspiratory pressure decrease. Both groups exhibited high incidences of neonatal respiratory distress syndrome. Neonatal complications resulting from meconium aspiration syndrome (MAS and sepsis were more common in the non-obstetric causes group; however, neurological development impairment was more common in the obstetric causes group. Conclusion: Obstetric cause was associated with longer ventilator free days and fewer episodes of ARDS after delivery. Neonatal complications resulting from different etiologies of respiratory failure were found to differ. Keywords: Acute respiratory distress syndrome, Neonatal, Obstetric, Outcome, Respiratory failure

Anaesthesia for a patient with Eisenmenger′s syndrome undergoing caesarean section

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T Gurumurthy

2012-01-01

Full Text Available Eisenmenger′s syndrome is a cyanotic congenital heart disease that includes pulmonary hypertension with reversed or bidirectional shunt associated with septal defects or patent ductus arteriosus. The decreased systemic vascular resistance associated with pregnancy increases the degree of right to left shunting, thereby carrying substantial risk to both the mother and the foetus. The maternal mortality rate of pregnancy in the presence of Eisenmenger′s syndrome is reported to be as high as 30-70%. We present a case of a 22-year-old primigravida with Eisenmenger′s syndrome who gave birth at 37 weeks of gestation via caesarean section to a live female baby under general anaesthesia. On the third post-operative day, the patient developed tachycardia, tachypnoea, hypotension and decrease in oxygen saturation despite supplemental oxygen, clinically suspected pulmonary thromboembolism. We describe the anaesthetic management for caesarean section and its complications in a patient with Eisenmenger′s syndrome. Although pregnancy should be discouraged in women with Eisenmenger′s syndrome, it can be successful.

MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options.

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El-Hattab, Ayman W; Adesina, Adekunle M; Jones, Jeremy; Scaglia, Fernando

2015-01-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. MELAS syndrome is a multi-organ disease with broad manifestations including stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature. The most common mutation associated with MELAS syndrome is the m.3243A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNA(Leu(UUR)). The m.3243A>G mutation results in impaired mitochondrial translation and protein synthesis including the mitochondrial electron transport chain complex subunits leading to impaired mitochondrial energy production. The inability of dysfunctional mitochondria to generate sufficient energy to meet the needs of various organs results in the multi-organ dysfunction observed in MELAS syndrome. Energy deficiency can also stimulate mitochondrial proliferation in the smooth muscle and endothelial cells of small blood vessels leading to angiopathy and impaired blood perfusion in the microvasculature of several organs. These events will contribute to the complications observed in MELAS syndrome particularly the stroke-like episodes. In addition, nitric oxide deficiency occurs in MELAS syndrome and can contribute to its complications. There is no specific consensus approach for treating MELAS syndrome. Management is largely symptomatic and should involve a multidisciplinary team. Unblinded studies showed that l-arginine therapy improves stroke-like episode symptoms and decreases the frequency and severity of these episodes. Additionally, carnitine and coenzyme Q10 are commonly used in MELAS syndrome without proven efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal capital and the metabolic ghetto: An evolutionary perspective on the transgenerational basis of health inequalities.

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Wells, Jonathan C K

2010-01-01

There is particular interest in understanding socioeconomic and ethnic variability in health status. The developmental origins of disease hypothesis emphasize the importance of growth patterns across the life-course in relation to noncommunicable disease risk. The physiological components of cardiovascular risk, collectively termed the metabolic syndrome, derive in part from a disparity between the homeostatic "metabolic capacity" of vital organs and the "metabolic load" induced by large tissue masses, a rich diet and sedentary behavior. From an evolutionary perspective, the risk of such disparity is decreased by maternal physiology regulating offspring growth trajectory during gestation and lactation. Maternal capital, defined as phenotypic resources enabling investment in the offspring, allows effective buffering of the offspring from nutritional perturbations and represents the environmental niche initially occupied by the offspring. Offspring growth patterns are sensitive to the magnitude of maternal capital during early windows of plasticity. Offspring life-history strategy can then respond adaptively to further factors across the life-course, but only within the context of this initial maternal influence on growth. Maternal somatic capital is primarily gained or lost across generations, through variable rates of fetal and infant growth. I argue that the poor nutritional experience of populations subjected to colonialism resulted in a systematic loss of maternal capital, reflected in downward secular trends in stature. Accelerating the recovery of somatic capital within generations overloads metabolic capacity and exacerbates cardiovascular risk, reflected in increased disease rates in urbanizing and emigrant populations. Public health policies need to benefit metabolic capacity without exacerbating metabolic load. 2009 Wiley-Liss, Inc.

Familial cryptic translocation in Angelman syndrome

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Weyerts, L.K.; Wiley, J.E.; Loud, K.M. [ECU School of Medicine, Greenville, NC (United States)] [and others

1994-09-01

The majority of patients with Angelman syndrome have been shown to have a cytogenetic or molecular deletion on the maternally derived chromosome 15. We report on a case of Angelman syndrome in which this deletion occurs as an unbalanced cryptic translocation involving chromosomes 14 and 15. The proband was diagnosed clinically as having Angelman syndrome. Multiple cytogenetic studies were done without detecting any deletion. When DNA probes (Oncor) specific for the Prader Willi/Angelman locus became available, the patient was restudied and found to be deleted for {open_quotes}region A{close_quotes} (D15S11) but not for {open_quotes}region B{close_quotes} (GABRB3). No other abnormality was detected. The proband`s mother was then studied. The chromosome 15 marker probe and D15S11 were detected on different chromosomes. Using alpha-satellite probes, a cryptic 14;15 translocation was uncovered. This balanced translocation was also found to be carried by the sister of the proband. This case, along with a case presented at the 1993 ASHG meeting, illustrates the need for using acrocentric probes when studying Angelman syndrome patients. The proband was studied using additional probes specific for this region and found to be deleted for SNRPN but not for D15S10. The breakpoint of the translocation in this patient delineates the smallest deletion of the Angelman syndrome region reported to date and therefore may represent the specific gene involved.

Severe neonatal-onset panniculitis in a female infant with Prader-Willi syndrome.

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Sakthivel, Muthukumar; Hughes, Stephen M; Riley, Phil; Arkwright, Peter D; Mukherjee, Anindya; Ramsden, Simon; Urquhart, Jill; Crow, Yanick J