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Sample records for albright hereditary osteodystrophy

  1. Bariatric surgery in an obese patient with Albright hereditary osteodystrophy: a case report

    OpenAIRE

    Ferrario, Chiara; Gastaldi, Giacomo; Portmann, Luc; Giusti, Vittorio

    2013-01-01

    Introduction We report for the first time the case of a patient with Albright hereditary osteodystrophy and pseudopseudohypoparathyroidism who underwent a Roux-en-Y gastric bypass. Case presentation A 26-year-old obese Caucasian woman with Albright hereditary osteodystrophy with pseudopseudohypoparathyroidism (heterozygous mutation (L272F) in GNAS1 exon 10 on molecular analysis) was treated with gastric bypass. She had the classical features of Albright hereditary osteodystrophy: short statur...

  2. Mutations of the Gs α-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis

    International Nuclear Information System (INIS)

    Affected members of most kindreds with Albright hereditary osteodystrophy have a partial deficiency of functional Gs, the guanine nucleotide-binding protein that stimulates adenylyl cyclase. By use of the polymerase chain reaction to amplify genomic fragments with the attachment of a high-melting G+C-rich region (GC clamp) and analysis of these fragments by denaturing gradient gel electrophoresis, heterozygous mutations in the Gs α-subunit at the donor splice junction of intron 10 and a coding frameshift created by a single base deletion within exon 10. The findings illustrate the heterogeneity of genetic defects in Albright hereditary osteodystrophy and the usefulness of the polymerase chain reaction-denaturing gradient gel electrophoresis method to search rapidly for mutations in a large candidate gene

  3. Genetic deficiency of the α subunit of the guanine nucleotide-binding protein G/sub s/ as the molecular basis for Albright hereditary osteodystrophy

    International Nuclear Information System (INIS)

    Patients who have pseudohypoparathyroidism type I associated with Albright hereditary osteodystrophy commonly have a genetic deficiency of the α subunit of the G protein that stimulated adenylyl cyclase αG/sub s/. To discover the molecular mechanism that causes αG/sub s/ deficiency in these patients, the authors examined eight kindreds with one or more members affected with Albright hereditary osteodystrophy or pseudohypoparathyroidism and αG/sub s/ deficiency. In these families, αG/sub s/, deficiency and the Albright hereditary osteodystrophy phenotype were transmitted together in a dominant inheritance pattern. Using a cDNA hybridization probe for αG/sub s/, restriction analysis with several analysis with several endonucleases showed no abnormalities of restriction fragments or gene dosage. RNA blot and dot blot analysis of total RNA from cultured fibroblasts obtained from the patients revealed ∼ 50% reduced mRNA levels for αG/sub s/ in affected members of six of the pedigrees but normal levels in affected members of the two other pedigrees, compared to mRNA levels in fibroblasts from unaffected individuals. By contrast, mRNA levels encoding the α subunit of the G protein that inhibits adenylyl cyclase were not altered. These findings suggest that several molecular mechanisms produce αG/sub s/ deficiency in patients with pseudohypoparathyroidism type Ia and that major gene rearrangements or deletions are not a common cause for αG/sub s/ deficiency in pseudohypoparathyroidism type I

  4. Bilateral simultaneous disc edema and cataract associated with Albright hereditary osteodystrophy

    Directory of Open Access Journals (Sweden)

    Sabyasachi Sengupta

    2012-01-01

    Full Text Available A 16-year-old female presented with poor vision in both eyes. On clinical examination, she had bilateral cataracts and optic disc edema bilaterally on ultrasound examination. Extensive intracranial calcification was evident on computerized tomography. Physical examination revealed short stature, rounded chubby face, dental abnormalities, brachydactyly, and obesity. Laboratory evidence of hypocalcemia, hyperphosphatemia, elevated parathyroid hormone level (indicative of pseudohypoparathyroidism along with the constellation of phenotypical characteristics lead to a diagnosis of Albright′s hereditary osteodystrophy. This case is being presented to increase awareness regarding presence of coexisting and previously undiagnosed hypocalcemic syndromes in pediatric cataracts. The role of an ophthalmologist may be pivotal in diagnosing such an entity as documented in the present case.

  5. Screening of PRKAR1A and PDE4D in a Large Italian Series of Patients Clinically Diagnosed With Albright Hereditary Osteodystrophy and/or Pseudohypoparathyroidism.

    Science.gov (United States)

    Elli, Francesca Marta; Bordogna, Paolo; de Sanctis, Luisa; Giachero, Federica; Verrua, Elisa; Segni, Maria; Mazzanti, Laura; Boldrin, Valentina; Toromanovic, Alma; Spada, Anna; Mantovani, Giovanna

    2016-06-01

    The cyclic adenosine monophosphate (cAMP) intracellular signaling pathway mediates the physiological effects of several hormones and neurotransmitters, acting by the activation of G-protein coupled receptors (GPCRs) and several downstream intracellular effectors, including the heterotrimeric stimulatory G-protein (Gs), the cAMP-dependent protein kinase A (PKA), and cAMP-specific phosphodiesterases (PDEs). Defective G-protein-mediated signaling has been associated with an increasing number of disorders, including Albright hereditary osteodistrophy (AHO) and pseudohypoparathyroidism (PHP), a heterogeneous group of rare genetic metabolic disorders resulting from molecular defects at the GNAS locus. Moreover, mutations in PRKAR1A and PDE4D genes have been recently detected in patients with acrodysostosis (ACRDYS), showing a skeletal and endocrinological phenotype partially overlapping with AHO/PHP. Despite the high detection rate of molecular defects by currently available molecular approaches, about 30% of AHO/PHP patients still lack a molecular diagnosis, hence the need to screen patients negative for GNAS epi/genetic defects also for chromosomal regions and genes associated with diseases that undergo differential diagnosis with PHP. According to the growing knowledge on Gsα-cAMP signaling-linked disorders, we investigated our series of patients (n = 81) with a clinical diagnosis of PHP/AHO but negative for GNAS anomalies for the presence of novel genetic variants at PRKAR1A and PDE4D genes. Our work allowed the detection of 8 novel missense variants affecting genes so far associated with ACRDYS in 9 patients. Our data further confirm the molecular and clinical overlap among these disorders. We present the data collected from a large series of patients and a brief review of the literature in order to compare our findings with already published data; to look for PRKAR1A/PDE4D mutation spectrum, recurrent mutations, and mutation hot spots; and to identify specific

  6. Osteodystrophy in liver cirrhosis

    International Nuclear Information System (INIS)

    In order to investigate the osteodystrophy in liver cirrhosis, 21 liver cirrhotic patients having no malignancy and normal renal function were examined by 99m Tc Methylene Diphosphonate (MDP) bone scintigraphy. The cirrhotic subjects consisted of 14 males and 7 females. Their age was 31 - 80, average 55.7 years. The causes of their cirrhotic damage were 1 primary biliary cirrhosis, 9 alcoholic, 2 HB viral and 9 cryptogenic. The contents of their illness showed 9 cases in A, 4 in B and 8 in C of Child's classification. Abnormal hot spot(s) on bone in the cirrhotics could be observed very frequently in 99m Tc MDP bone scintigraphy (47.6 %; 10/21 cases). Those spots were seen more frequently in female and advanced stage of cirrhosis. The number of spot(s) increased also in advanced liver cirrhosis. Serum Ca, P and PTH were in normal range. All of three vitamin D3 fractions decreased and especially 1,25 (OH)2D3 was depressed more in scinti-positive cases. Metacarpal bone X-p with an alumimum step wedge as a reference was analyzed by a microdensitometry (MD) method (Inoue T et al) and the pattern of osteopathy (i.e. porosis, malacia and poromalacia) was examined according to Sumi Y et al. MD method was not known yet if there was any definite correlation with bone scintigraphy and the osteopathic pattern belonged to border categories. In conclusion, more attension on hepatic osteodystrophy will be significantly necessary due to the fact that it has been found very frequently in liver cirrhosis. 99m Tc MDP bone scintigraphy is a good means for detection of the hepatic osteodystrophy. (author)

  7. McCune-Albright syndrome

    OpenAIRE

    Collins Michael T; Dumitrescu Claudia E

    2008-01-01

    Abstract McCune-Albright syndrome (MAS) is classically defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP). It is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. FD can involve a single or multiple skeletal sites and presents with a limp and/or pain, and, occasionally, a pathologic fracture. Scoliosis is common and may be progressive. In addition to PP (vaginal bleeding or spotting and development of...

  8. Nutritional fibrous osteodystrophy in goats

    Directory of Open Access Journals (Sweden)

    Paulo M Bandarra

    2011-10-01

    Full Text Available Seven out of 25 goats from a southern Brazilian flock developed nutritional fibrous osteodystrophy. Affected animals were younger than 1 year of age and were confined in stalls and fed a concentrate ration containing 1:6 calcium:phosphorus ratio. The remaining flock (35 goats was managed at pasture and showed no disease. Clinical signs were characterized by mandibular and maxillary enlargements, varying degrees of mouth opening and protruding tongue, dyspnea, apart of abnormalities of prehension and mastication. Affected animals had increased seric levels of phosphorus and parathormone, as well as higher alkaline phosphatase activity. Postmortem examination on three succumbed goats revealed bilateral enlargement of the maxilla and mandibula, and loose teeth, apart of multiple incomplete rib fractures in one of them. Severe diffuse proliferation of loose connective tissue surrounded the osteoid trabeculae, many of which were partially or completely non-mineralized. Mineralized osteoid trabeculae showed osteoclasts in the Howship's lacunae.

  9. McCune-Albright syndrome

    Directory of Open Access Journals (Sweden)

    Collins Michael T

    2008-05-01

    Full Text Available Abstract McCune-Albright syndrome (MAS is classically defined by the clinical triad of fibrous dysplasia of bone (FD, café-au-lait skin spots, and precocious puberty (PP. It is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. FD can involve a single or multiple skeletal sites and presents with a limp and/or pain, and, occasionally, a pathologic fracture. Scoliosis is common and may be progressive. In addition to PP (vaginal bleeding or spotting and development of breast tissue in girls, testicular and penile enlargement and precocious sexual behavior in boys, other hyperfunctioning endocrinopathies may be involved including hyperthyroidism, growth hormone excess, Cushing syndrome, and renal phosphate wasting. Café-au-lait spots usually appear in the neonatal period, but it is most often PP or FD that brings the child to medical attention. Renal involvement is seen in approximately 50% of the patients with MAS. The disease results from somatic mutations of the GNAS gene, specifically mutations in the cAMP regulating protein, Gs alpha. The extent of the disease is determined by the proliferation, migration and survival of the cell in which the mutation spontaneously occurs during embryonic development. Diagnosis of MAS is usually established on clinical grounds. Plain radiographs are often sufficient to make the diagnosis of FD and biopsy of FD lesions can confirm the diagnosis. The evaluation of patients with MAS should be guided by knowledge of the spectrum of tissues that may be involved, with specific testing for each. Genetic testing is possible, but is not routinely available. Genetic counseling, however, should be offered. Differential diagnoses include neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm. Treatment is dictated by the tissues affected, and the extent to which they are affected. Generally, some form of surgical intervention

  10. Hereditary Neuropathies

    Science.gov (United States)

    ... group of inherited disorders affecting the peripheral nervous system. The hereditary neuropathies are divided into four major subcategories: hereditary motor and sensory neuropathy, hereditary sensory neuropathy, hereditary motor neuropathy, and ...

  11. [Recovery of Cushing syndrome revealing McCune-Albright syndrome].

    Science.gov (United States)

    Halioui-Louhaichi, S; Dridi, Y; Azzabi, O; Selmi, I; Fetni, I; Siala, N; Maherzi, A

    2016-01-01

    Cushing syndrome (CS) is a rare feature of McCune-Albright syndrome. Treatments consist of bilateral adrenalectomy followed by lifelong glucocorticoid and mineralocorticoid treatment. However, cases of spontaneous remission of CS have been reported in the literature. We report a case of McCune-Albright syndrome with CS treated with metyrapone for 30 months with prolonged remission after a 12-year follow-up. Adrenalectomy may be avoided in some cases of CS caused by McCune-Albright syndrome. Metyrapone could be a good alternative to surgical treatment. PMID:26552628

  12. Incomplete McCune-Albright Syndrome: A Case Report

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    Nagehan Aslan

    2014-08-01

    Full Text Available Fibrous dysplasia of bone is a genetic, non-inheritable disease that can cause bone pain, bone deformities and fracture. It has a large clinic spectrum from benign monostotic fibrous dysplasia to McCune-Albright syndrome. Rare McCune-Albright syndrome is characterized by precocious puberty, cafe au lait spots and fibrous dysplasia. Herein we presented a case who was preferred to hospital with pathological fractures and diagnosed with Incomplet McCune Albright syndrome because of the lack of endocrine hyperfunction and developed early puberty at clinical course.

  13. Mandibular brown tumor in renal osteodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin Woo; Choi, Bo Ram; Huh, Kyung Hoe; Yi, Won Jin; Choi, Soon Chul [Department of Oral and Maxillofacial Radiology, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Gang, In Tae [Department of Oral and Maxillofacial Surgery, Kangnam Sacred Heart Hospital, Hallym Medical Center, Seoul (Korea, Republic of)

    2008-12-15

    Brown tumor is a histologically benign lesion that is a serious complication of renal osteodystrophy because it may result in severe deformity and discomfort. We report a case of brown tumor, which occurred in a 35-year-old woman with chronic renal failure, who had been treated with hemodialysis for 14 years. The lesion was found on the lingual side of the mandible. Standard panoramic radiograph showed generally decreased bone mineral density, loss of lamina dura, and thin cortical plates. Computed tomography (CT) revealed multilocular expansible lesions with heterogeneous attenuation in the anterior mandible, as well as generalized trabecular alteration with homogeneous sclerosis, and thinning or obliteration of cortical plates. Excision of the mandibular lesion and curettage of the affected bone were performed.

  14. Bone Canopies in Pediatric Renal Osteodystrophy

    Science.gov (United States)

    Pereira, Renata C.; Andersen, Thomas L.; Friedman, Peter A.; Tumber, Navdeep; Salusky, Isidro B.; Wesseling-Perry, Katherine

    2016-01-01

    Pediatric renal osteodystrophy (ROD) is characterized by changes in bone turnover, mineralization, and volume that are brought about by alterations in bone resorption and formation. The resorptive and formative surfaces on the cancellous bone are separated from the marrow cavity by canopies consisting of a layer of flat osteoblastic cells. These canopies have been suggested to play a key role in the recruitment of osteoprogenitors during the process of bone remodeling. This study was performed to address the characteristics of the canopies above bone formation and resorption sites and their association with biochemical and bone histomorphometric parameters in 106 pediatric chronic kidney disease (CKD) patients (stage 2–5) across the spectrum of ROD. Canopies in CKD patients often appeared as thickened multilayered canopies, similar to previous reports in patients with primary hyperparathyroidism. This finding contrasts with the thin appearance reported in healthy individuals with normal kidney function. Furthermore, canopies in pediatric CKD patients showed immunoreactivity to the PTH receptor (PTHR1) as well as to the receptor activator of nuclear factor kappa-B ligand (RANKL). The number of surfaces with visible canopy coverage was associated with plasma parathyroid hormone (PTH) levels, bone formation rate, and the extent of remodeling surfaces. Collectively, these data support the conclusion that canopies respond to the elevated PTH levels in CKD and that they possess the molecular machinery necessary to respond to PTH signaling. PMID:27045269

  15. Bone end sclerosis in renal osteodystrophy simulating osteonecrosis

    International Nuclear Information System (INIS)

    Osteosclerosis of the bone ends is an unusual manifestation of renal osteodystrophy. In evaluating this finding one should be careful to exclude clinical and radiographic evidence for osteonecrosis. In the two known cases of this entity, bone end sclerosis has been found to develop over one to two years with symmetrical involvement of multiple bones. (orig.)

  16. Hansen's disease with McCune–Albright syndrome

    OpenAIRE

    Hari Kumar KVS; Dhull, P; Bisht, Y. S.

    2012-01-01

    McCune-Albright syndrome (MAS) comprises a triad of fibrous dysplasia of bone, cafι-au-lait macule, and endocrinopathy. The disease is due to activating mutation of G protein-coupled receptor leading to hyperfunction of glands. Hansen′s disease is caused by infection with Mycobacterium leprae and is seen with underlying immunosuppressed conditions in genetically predisposed individuals. We recently encountered a patient with Hansen′s disease along with underlying MAS and report the same in th...

  17. Hereditary pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Richard M Charnley

    2003-01-01

    Hereditary pancreatitis is an autosomal dominant condition,which results in recurrent attacks of acute pancreatitis,progressing to chronic pancreatitis often at a young age.The majority of patients with hereditary pancreatitis expressone of two mutations (R122H or N29I) in the cationictrypsinogen gene (PRSS1 gene). It has been hypothesisedthat one of these mutations, the R122H mutation causespancreatitis by altering a trypsin recognition site sopreventing deactivation of trypsin within the pancreas andprolonging its action, resulting in autodigestion. Families withthese two mutations have been identified in many countriesand there are also other rarer mutations, which have alsobeen linked to hereditary pancreatitis.Patients with hereditary pancreatitis present in the sameway as those with sporadic pancreatitis but at an earlierage. It is common for patients to remain undiagnosed formany years, particularly ifthey present with non-specificsymptoms. Hereditary pancreatitis should always beconsidered in patients who present with recurrent pancreatitiswith a family history of pancreatic disease. If patients withthe 2 common mutations are compared, those with theR122H mutation are more likely to present at a younger ageand are more likely to require surgical intervention than thosewith N29I. Hereditary pancreatitis carries a 40 % lifetimerisk of pancreatic cancer with those patients aged between50 to 70 being most at risk in whom screening tests maybecome important.

  18. Untersuchung der Knochen bei hepatischer Osteodystrophie am MDR2-/--Mausmodell

    OpenAIRE

    Lau, Yvonne

    2014-01-01

    Osteoporosis is the most frequent bone disease in Germany with approximately six million people being affected by it. For this reason osteoporosis is a most relevant topic both for society in general and the health system in particular. In daily clinical practice, it could be observed that patients suffering from chronic liver disease in many cases also suffer from disturbances in bone metabolism. This observation is also referred to as hepatic osteodystrophy, with osteoporosis as its most...

  19. Síndrome de McCune Albright

    OpenAIRE

    Milvia Castillo Guerrero; Belkis Villegas Batista; Omar De La Paz Marín

    2014-01-01

    El síndrome de McCune-Albright es una enfermedad esporádica de causa genética, no hereditaria, clínicamente caracterizada por displasia fibrosa poliostótica, manchas de color café con leche y desórdenes endocrinos, tales como hipertiroidismo y pubertad precoz. Se reporta el caso de un paciente masculino de 10 años, que presentó múltiples fracturas óseas desde los seis meses de edad, hipertiroidismo y desnutrición severa, que causaron retardo en su crecimiento y desarrollo. El proceso de diagn...

  20. Hereditary Angioedema

    DEFF Research Database (Denmark)

    Abdel-Karim, Omar; Dizdarevic, Adis; Bygum, Anette

    2014-01-01

    Hereditary angioedema is an inherited disease that causes periodic swelling attacks, which can be life threatening and have a major effect on a patient's life. Studies have shown that home therapy for angioedema reduces disease severity, leads to faster relief of symptoms, and improves quality of...

  1. Diabetes and disordered bone metabolism (diabetic osteodystrophy): time for recognition.

    Science.gov (United States)

    Epstein, S; Defeudis, G; Manfrini, S; Napoli, N; Pozzilli, P

    2016-06-01

    Diabetes and osteoporosis are rapidly growing diseases. The link between the high fracture incidence in diabetes as compared with the non-diabetic state has recently been recognized. While this review cannot cover every aspect of diabetic osteodystrophy, it attempts to incorporate current information from the First International Symposium on Diabetes and Bone presentations in Rome in 2014. Diabetes and osteoporosis are fast-growing diseases in the western world and are becoming a major problem in the emerging economic nations. Aging of populations worldwide will be responsible for an increased risk in the incidence of osteoporosis and diabetes. Furthermore, the economic burden due to complications of these diseases is enormous and will continue to increase unless public awareness of these diseases, the curbing of obesity, and cost-effective measures are instituted. The link between diabetes and fractures being more common in diabetics than non-diabetics has been widely recognized. At the same time, many questions remain regarding the underlying mechanisms for greater bone fragility in diabetic patients and the best approach to risk assessment and treatment to prevent fractures. Although it cannot cover every aspect of diabetic osteodystrophy, this review will attempt to incorporate current information particularly from the First International Symposium on Diabetes and Bone presentations in Rome in November 2014. PMID:26980458

  2. Hereditary hemochromatosis

    International Nuclear Information System (INIS)

    To describe the clinical and laboratory features of hereditary hemochromatosis associated liver disease in a tertiary care hospital. Study Design: Observational study. Place and Duration of Study: The Aga Khan University Hospital, Karachi, from January 2002 to October 2012. Methodology: Charts of patients with Hereditary Hemochromatosis (HHC) were reviewed. Data collected and analyzed consisting of clinical presentations, liver function tests, serum ferritin, transferrin saturation, hepatic imaging and histology in patients with HHC. Results: A total of 22 patients were identified as having hemochromatosis. All subjects were men with a mean age of 53 ± 9.2 years at the time of diagnosis. The most common presentation was skin pigmentation seen in 17 (77%), followed by loss of libido/ impotence in 11 (50%) and then arthralgias in 10 (45%) and weakness in 6 (27%). Eleven (50%) subjects had diabetes mellitus and one subject had concomitant cardiac involvement. Patients with diabetes were diagnosed earlier as compared to those without it. Eighteen (81%) subjects had cirrhosis at the time of diagnosis. Serum iron was 164 ± 53 ug/dl, ferritin 3391 ± 1960 ug/L, TIBC 202 ± 61 ug/dl and transferrin saturation 76.8 ± 14%. Liver biopsy was done in 10 (45%) and using Pearls stain histopathological features were consistent with hemochromatosis and none had carcinoma. Only 3 (14%) patients had regular phlebotomy. Conclusion: Hemochromatosis is not a rare disease in Pakistan and should be looked in those subjects whose liver function tests are deranged. (author)

  3. [Hereditary angioedema].

    Science.gov (United States)

    Bouchard, Laura J; Hyry, Heli; Meri, Seppo

    2012-01-01

    Hereditary angioedema (HAE) is a rare autosomal dominant disease characterized by episodic swelling of the face, extremities, larynx, gastrointestinal tract or genitals. Three different subtypes have been identified so far. Type I and II HAE are caused by mutations in the C1 inhibitor gene leading to decreased or dysfunctional C1 inhibitor, respectively. Type III is caused by a mutation in the coagulation factor XII. In addition, acquired forms or forms with no known etiology exist. Increased bradykinin production leading to increased vessel permeability is common to all HAE types. Treatment of HAE has evolved dramatically during the last years as self-administration of C1 inhibitor concentrate and bradykinin-2 receptor antagonist icatibant have become available. PMID:23393928

  4. Pathophysiology and recent advances in the management of renal osteodystrophy.

    Science.gov (United States)

    Elder, Grahame

    2002-12-01

    Bone disease is observed in 75-100% of patients with chronic renal failure as the glomerular filtration rate (GFR) falls below 60 ml/minute. Hyperparathyroid (high turnover) bone disease is found most frequently followed by mixed osteodystrophy, low-turnover bone disease, and osteomalacia. With advancing renal impairment, "skeletal resistance" to parathyroid hormone (PTH) occurs. To maintain bone turnover, intact PTH (iPTH) targets from two to four times the upper normal range have been suggested, but whole PTH(1-84) assays indicate that amino-terminally truncated fragments, which accumulate in end-stage renal disease (ESRD), account for up to one-half of the measured iPTH. PTH levels and bone-specific alkaline phosphatase (BSAP) provide some information on bone involvement but bone biopsy and histomorphometry remains the gold standard. Calcitriol and calcium salts can be used to suppress PTH and improve osteomalacia but there is growing concern that these agents predispose to the development of vascular calcification, cardiovascular morbidity, low-turnover bone disease and fracture. Newer therapeutic options include less calcemic vitamin D analogues, calcimimetics and bisphosphonates for hyperparathyroidism, and sevelamer for phosphate control. Calcitriol and hormone-replacement therapy (HRT) have been shown to maintain bone mineral density (BMD) in certain patients with end-stage renal disease (ESRD). After renal transplantation, renal osteodystrophy generally improves but BMD often worsens. Bisphosphonate therapy may be appropriate for some patients at risk of fracture. When renal bone disease is assessed using a combination of biochemical markers, histology and bone densitometry, early intervention and the careful use of an increasing number of effective therapies can reduce the morbidity associated with this common problem. PMID:12469904

  5. Síndrome de McCune Albright

    Directory of Open Access Journals (Sweden)

    Milvia Castillo Guerrero

    2014-08-01

    Full Text Available El síndrome de McCune-Albright es una enfermedad esporádica de causa genética, no hereditaria, clínicamente caracterizada por displasia fibrosa poliostótica, manchas de color café con leche y desórdenes endocrinos, tales como hipertiroidismo y pubertad precoz. Se reporta el caso de un paciente masculino de 10 años, que presentó múltiples fracturas óseas desde los seis meses de edad, hipertiroidismo y desnutrición severa, que causaron retardo en su crecimiento y desarrollo. El proceso de diagnóstico fue demorado por su inusual forma de presentación, pero su evolución después de iniciar el tratamiento fue favorable. Se presenta el caso por la baja frecuencia de este trastorno, asociado a complicaciones endocrino-metabólicas graves que causan la muerte, si no se diagnostica y se trata precozmente

  6. Hereditary Spastic Paraplegia

    Science.gov (United States)

    ... there any treatment? What is the prognosis? What research is being done? Clinical Trials Organizations What is Hereditary Spastic Paraplegia? Hereditary spastic paraplegia (HSP), also called familial spastic paraparesis (FSP), refers to a group of inherited disorders that ...

  7. Is Pancreatic Cancer Hereditary?

    Science.gov (United States)

    ... Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? Cancer of the pancreas is a genetic ... found in cigarette smoke. The genetics of hereditary pancreatic cancer is a focus of research at Johns Hopkins. ...

  8. Cytokine accumulation in osteitis fibrosa of renal osteodystrophy

    Directory of Open Access Journals (Sweden)

    Duarte M.E.L.

    2002-01-01

    Full Text Available Bone marrow fibrosis occurs in association with a number of pathological states. Despite the extensive fibrosis that sometimes characterizes renal osteodystrophy, little is known about the factors that contribute to marrow accumulation of fibrous tissue. Because circulating cytokines are elevated in uremia, possibly in response to elevated parathyroid hormone levels, we have examined bone biopsies from 21 patients with end-stage renal disease and secondary hyperparathyroidism. Bone sections were stained with antibodies to human interleukin-1alpha (IL-1alpha, IL-6, IL-11, tumor necrosis factor-alpha (TNF-alpha and transforming growth factor-ß (TGF-ß using an undecalcified plastic embedding method. Intense staining for IL-1alpha, IL-6, TNF-alpha and TGF-ß was evident within the fibrotic tissue of the bone marrow while minimal IL-11 was detected. The extent of cytokine deposition corresponded to the severity of fibrosis, suggesting their possible involvement in the local regulation of the fibrotic response. Because immunoreactive TGF-ß and IL-6 were also detected in osteoblasts and osteocytes, we conclude that selective cytokine accumulation may have a role in modulating bone and marrow cell function in parathyroid-mediated uremic bone disease.

  9. Hypertrophic Osteodystrophy in Two Red Wolf (Canis rufus Pups

    Directory of Open Access Journals (Sweden)

    Jenessa L. Gjeltema

    2015-01-01

    Full Text Available A 6-month-old red wolf (Canis rufus pup presented for evaluation of progressive thoracic and pelvic limb lameness, joint swelling, and decreased body condition. Radiographic evaluation revealed medullary sclerosis centered at the metaphyses of multiple long bones, well-defined irregular periosteal proliferation, and ill-defined lucent zones paralleling the physes, consistent with hypertrophic osteodystrophy (HOD. Biopsies of affected bone revealed medullary fibrosis and new bone formation. The pup improved following treatment with nonsteroidal anti-inflammatories, opioids, and supportive care over the course of 4 weeks. Metaphyseal periosteal bone proliferation persisted until the animal was humanely euthanized several years later for poor quality of life associated with bilateral cranial cruciate ligament rupture. A second red wolf pup of 4.5 months of age presented for evaluation of lethargy, kyphotic posture, and swollen carpal and tarsal joints. Radiographs revealed bilateral medullary sclerosis and smooth periosteal reaction affecting multiple long bones, suggestive of HOD. Further diagnostics were not pursued in this case to confirm the diagnosis, and the clinical signs persisted for 4 weeks. In light of these two case reports, HOD should be recognized as a developmental orthopedic disease in growing red wolves.

  10. Course and differential diagnosis of the McCune-Albright syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Friedel, B.; Weickert, H.

    1986-05-01

    The McCune-Albright syndrome consists of a combination of fibrous dysplasia of bone and endocrine lesions with abnormalities of pigmentation. The condition is rare and may be missed, as happened in our case. The case showed extreme skeletal deformities, menarche at one year and peculiar histological appearances.

  11. Hereditary Hemorrhagic Telangiectasia - HHT

    Science.gov (United States)

    ... access catheters Vertebroplasty Women and vascular disease Women's health Social Media Facebook Twitter ... Hereditary Hemorrhagic Telangiectasia - HHT Interventional Radiologists Offer Non-surgical Treatment for Underdiagnosed Genetic Disorder ...

  12. McCune-Albright Syndrome: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Moein Mobini

    2014-04-01

    Full Text Available McCune-Albright syndrome (MAS is a rare, heterogenous, clinical condition caused by a rare genetic mutation. The disorder is more common in females and is characterized by a triad of cutaneous, bone and endocrine abnormalities.  We describe a girl patient with MAS having precocious puberty and multiple cafe-au-lait macules and deforming polyostotic fibrous dysplasia of bone. Clinical presentation and X-ray finding were strongly diagnostic for MAS, Patients with McCune-Albright syndrome reach the adult age with a significant burden of the disease that continuously reduces their quality of life. Skeletal deformities, fractures, hyperthyroidism, and hyperestrogenism are just few of the many challenges in the management of these patients. These disorders with close observation and early detection can be controlled.

  13. PROGRESS REPORT: COFIRING PROJECTS FOR WILLOW ISLAND AND ALBRIGHT GENERATING STATIONS

    International Nuclear Information System (INIS)

    During the period April 1, 2001-June 30, 2001, Allegheny Energy Supply Co., LLC (Allegheny) accelerated construction of the Willow Island cofiring project, completed the installation of foundations for the fuel storage facility, the fuel receiving facility, and the processing building. Allegheny received all processing equipment to be installed at Willow Island. Allegheny completed the combustion modeling for the Willow Island project. During this time period construction of the Albright Generating Station cofiring facility was completed, with few items left for final action. The facility was dedicated at a ceremony on June 29. Initial testing of cofiring at the facility commenced. This report summarizes the activities associated with the Designer Opportunity Fuel program, and demonstrations at Willow Island and Albright Generating Stations. It details the construction activities at both sites along with the combustion modeling at the Willow Island site

  14. [Renal osteodystrophy (3); its treatment in dialysis patients].

    Science.gov (United States)

    Ghitu, S; Oprisiu, R; Benamar, L; Said, S; Tataru Albu, A; Arsenescu, I; el Esper, N; Morinière, P; Fournier, A

    2000-01-01

    The prevalence and the clinical gravity of the various histopathological varieties of renal osteodystrophy in dialysis patients depends on the severity of both the aluminium intoxication and that of hyperparathyroidism. The prevalence of bone pains, fractures and hypercalcemias are the highest in adynamic bone diseases (ABD) with severe aluminium intoxication, then in osteitis fibrosa and mixed osteopathy, in the ABD with moderate aluminium intoxication and rare in the mild lesion in spite of similar moderate aluminium intoxication. In the absence of aluminium intoxication, hypercalcemia and hyperphosphatemia prevalence is higher only when intact PTH is more that 4 times the upper limit of normal. When PTH is between 1 and 2 folds the ULN this prevalence is null and bone mineral density is the highest. 2. The low turnover aluminic bone diseases (osteomalacic or adynamic) will be cured by long term deferoxamine treatment. The hazards of such treatment justify the performance of a bone biopsy to ensure the diagnosis. Their prevention relies on adequate treatment of tapwater and definitive exclusion of long term administration of aluminum phosphate binders. 3. Non aluminic osteomalacia will be treated according to the same guidelines given for the uremic patients before dialysis. 4. Non aluminic adynamic bone disease will be cured by means aiming at stimulating PTH secretion as discontinuing 1 alpha hydroxylated vitamin D derivatives, and, if there is no hyperphosphatemia by discontinuation of calcium supplement. In case of hyperphosphatemia in dialysis patients CaCO3 doses have to be nevertheless increased after the dialysate calcium concentration (DCa) has been decreased in order to induce a negative perdialytic calcium balance for PTH secretion stimulation. In the near future substitution of CaCO3 by non calcemic non aluminic phosphate binders will suffice. 5. Osteitis fibrosa due to hyperparathyroidism will be treated first by securing an optimal vitamin D

  15. [Diagnosis of hereditary angioedema].

    Science.gov (United States)

    Bouillet, Laurence

    2015-01-01

    Hereditary angioedema is a rare disease, potentially life-threatening. It requires a specific treatment. Angioedema without wheals associated with abdominal attacks are very specific of this disease. Antigenemy and functional C1Inhibitor assays are necessary for the diagnosis. The hereditary angioedema with normal C1Inh (type III) is a diagnostic challenge. Bradykinin, secondary to kallikrein-kinin system activation is the key mediator of hereditary angioedema. Female are more symptomatic. Attacks can be induced by menstruations, pregnancies or contraceptive pills. PMID:25511656

  16. MOMO Syndrome with Holoprosencephaly and Cryptorchidism: Expanding the Spectrum of the New Obesity Syndrome

    OpenAIRE

    Ram Kumar Marwaha; Inusha Panigrahi; Sheetal Sharda

    2011-01-01

    There are multiple genetic disorders with known or unknown etiology grouped under obesity syndromes. Inspite of having multisystem involvement and often having a characteristic presentation, the understanding of the genetic causes in the majority of these syndromes is still lacking. The common obesity syndromes are Bardet-Biedl, Prader-Willi, Alstrom, Albright's hereditary osteodystrophy, Carpenter, Rubinstein-Taybi, Fragile X, and Börjeson-Forssman-Lehman syndrome. The list is ever increasin...

  17. Characteristic Height Growth Pattern in Patients with Pseudohypoparathyroidism: Comparison between Type 1a and Type 1b

    OpenAIRE

    Kinoshita, Kaori; Minagawa, Masanori; Anzai, Michiko; Sato, Yumiko; Kazukawa, Itsuro; Shimohashi, Kyoko; Ota, Setsuo; Kohno, Yoichi

    2007-01-01

    Pseudohypoparathyroidism (PHP) is a metabolic disorder characterized by organ resistance to the action of parathyroid hormone. PHP type 1 is subclassified into two apparent disorders, type 1a (PHP1a) and type 1b (PHP1b). Patients with PHP1a show Albright hereditary osteodystrophy including short stature. Patients with PHP1b have no such skeletal defects, however, literature regarding the growth of PHP1b is not currently available. We evaluated growth charts of PHP patients, including four PHP...

  18. Learning about Hereditary Hemochromatosis

    Science.gov (United States)

    ... and Its Implications Meeting A 1997 ELSI Report Learning About Hereditary Hemochromatosis What do we know about ... and treatment information. Hosted by the Dolan DNA Learning Center at Cold Spring Harbor Laboratory. Iron Overload ...

  19. Hereditary Pancreatic and Hepatobiliary Cancers

    OpenAIRE

    Ashraf Haddad; Kowdley, Gopal C; Timothy M. Pawlik; Cunningham, Steven C.

    2011-01-01

    Hereditary etiologies of pancreatic and hepatobiliary cancers are increasingly recognized. An estimated >10% of pancreatic and increasing number of hepatobiliary cancers are hereditary. The cumulative risk of hereditary pancreatic cancer ranges from measurable but negligible in cystic fibrosis to a sobering 70% in cases of hereditary pancreatitis. Candidates for pancreatic cancer surveillance are those with a risk pancreatic cancer estimated to be >10-fold that of the normal population. Scree...

  20. Burnout control at the Albright coal-waste-bank fire. Rept. of investigations/1991

    International Nuclear Information System (INIS)

    Burnout Control is a process developed by the U.S. Bureau of Mines for accelerating the burning of wasted coal fires in situ, while at the same time controlling the heat and fumes produced. The Albright fire project is a first field trial of Burnout Control as applied to a coal waste bank. An exhaust ventilation system was designed and constructed and then operated over a 1-year period at the site of an existing abandoned mine land fire near the town of Albright, W.V. While predicted exhaust gas temperatures of 900 C and thermal power levels of 5 MW were achieved at 20- to 30-in H2O vacuum levels, problems were encountered with engineering designs, equipment breakdown, and fuel-rich combustion that curtailed the time period of satisfactory operation. Effective afterburning of the exhaust gases (as they were drawn from the bank) corrected the problems associated with combustion stoichiometry and led to high thermal outputs. It is believed that with (1) improvements in engineering design and construction, (2) better control of the afterburning process, and (3) the use of conventional stack gas air-pollution controls, Burnout Control can be applied successfully to a coal waste bank fire

  1. Osteodystrophy in liver cirrhosis. Its demonstration by 99m Tc methylene diphosphonate bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Sezai, Shu-ichi; Ishizawa, Suguru; Yoshino, Katsumasa

    1987-10-01

    In order to investigate the osteodystrophy in liver cirrhosis, 21 liver cirrhotic patients having no malignancy and normal renal function were examined by 99m Tc Methylene Diphosphonate (MDP) bone scintigraphy. The cirrhotic subjects consisted of 14 males and 7 females. Their age was 31 - 80, average 55.7 years. The causes of their cirrhotic damage were 1 primary biliary cirrhosis, 9 alcoholic, 2 HB viral and 9 cryptogenic. The contents of their illness showed 9 cases in A, 4 in B and 8 in C of Child's classification. Abnormal hot spot(s) on bone in the cirrhotics could be observed very frequently in 99m Tc MDP bone scintigraphy (47.6 %; 10/21 cases). Those spots were seen more frequently in female and advanced stage of cirrhosis. The number of spot(s) increased also in advanced liver cirrhosis. Serum Ca, P and PTH were in normal range. All of three vitamin D/sub 3/ fractions decreased and especially 1,25 (OH)/sub 2/D/sub 3/ was depressed more in scinti-positive cases. Metacarpal bone X-p with an alumimum step wedge as a reference was analyzed by a microdensitometry (MD) method (Inoue T et al) and the pattern of osteopathy (i.e. porosis, malacia and poromalacia) was examined according to Sumi Y et al. MD method was not known yet if there was any definite correlation with bone scintigraphy and the osteopathic pattern belonged to border categories. In conclusion, more attension on hepatic osteodystrophy will be significantly necessary due to the fact that it has been found very frequently in liver cirrhosis. 99m Tc MDP bone scintigraphy is a good means for detection of the hepatic osteodystrophy.

  2. Hereditary Hearing Loss.

    Science.gov (United States)

    Tran, LenhAnh P.; Grundfast, Kenneth M.

    1997-01-01

    This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

  3. Hereditary Angioedema in Childhood

    DEFF Research Database (Denmark)

    Kjaer, Line; Bygum, Anette

    2012-01-01

    Hereditary angioedema (HAE) is a rare inherited disease that is often difficult to diagnose. We report a case of a 9-year-old boy with a spontaneous mutation causing HAE, diagnosed after a life-threatening episode of angioedema of the head and upper respiratory tract after a 5-year history of...

  4. Hereditary and metabolic myelopathies.

    Science.gov (United States)

    Hedera, Peter

    2016-01-01

    Hereditary and metabolic myelopathies are a heterogeneous group of neurologic disorders characterized by clinical signs suggesting spinal cord dysfunction. Spastic weakness, limb ataxia without additional cerebellar signs, impaired vibration, and positional sensation are hallmark phenotypic features of these disorders. Hereditary, and to some extent, metabolic myelopathies are now recognized as more widespread systemic processes with axonal loss and demyelination. However, the concept of predominantly spinal cord disorders remains clinically helpful to differentiate these disorders from other neurodegenerative conditions. Furthermore, metabolic myelopathies are potentially treatable and an earlier diagnosis increases the likelihood of a good clinical recovery. This chapter reviews major types of degenerative myelopathies, hereditary spastic paraplegia, motor neuron disorders, spastic ataxias, and metabolic disorders, including leukodystrophies and nutritionally induced myelopathies, such as vitamin B12, E, and copper deficiencies. Neuroimaging studies usually detect a nonspecific spinal cord atrophy or demyelination of the corticospinal tracts and dorsal columns. Brain imaging can be also helpful in myelopathies caused by generalized neurodegeneration. Given the nonspecific nature of neuroimaging findings, we also review metabolic or genetic assays needed for the specific diagnosis of hereditary and metabolic myelopathies. PMID:27430441

  5. [Hereditary transthyretin amyloidosis].

    Science.gov (United States)

    Hund, E

    2014-10-01

    Hereditary amyloidosis is an autosomal dominant fatal multisystem disease caused by extracellular deposition of misfolded proteins and, therefore represents a hereditary protein folding or deposition disease that leads to progressive organ damage and eventually death. In most instances mutations within the transthyretin gene are the underlying cause. The main manifestation is a rapidly progressing axonal sensorimotor and autonomic polyneuropathy (familial amyloid polyneuropathy, FAP). Cardiac involvement is frequent in FAP and additional manifestations include the gastrointestinal tract and the eyes. A second manifestation type is cardiomyopathy with little or no polyneuropathy (familial amyloid cardiomyopathy, FAC). For therapy, orthotopic liver transplantation has been established for 25 years. Recently, the oral agent tafamidis, a transthyretin stabilizer, was licensed for treatment of stage 1 polyneuropathy. Additional treatment options are currently being studied. PMID:25123367

  6. Hereditary breast cancer

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie;

    2014-01-01

    Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight into the t......Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

  7. A Rare Cause of Acromegaly: Short Review of McCune Albright Syndrome

    Directory of Open Access Journals (Sweden)

    Yusuf Aydın

    2009-06-01

    Full Text Available McCune-Albright syndrome (MAS is characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules, and hyperfunctioning endocrinopathies, including growth hormone (GH excess. Acromegaly, as a manifestation of endocrine hyperfunction with MAS is uncommon. We report a 34-year-old man with MAS and acromegaly, in whom surgical removal of the pituitary tumour has been technically difficult because of bone deformities. A combination of a long-acting somatostatin analogue (Sandostatin LAR and external irradiation were therefore used as treatment. Acromegaly associated with MAS is very rarely seen, and has been the subject of approximately 70 published reports. We present a case of acromegaly associated with MAS and a brief survey of relevant literature. Turk Jem 2009; 13: 13-5

  8. Genetics Home Reference: hereditary fructose intolerance

    Science.gov (United States)

    ... Genetics Home Health Conditions hereditary fructose intolerance hereditary fructose intolerance Enable Javascript to view the expand/collapse ... Print All Open All Close All Description Hereditary fructose intolerance is a condition that affects a person's ...

  9. Radiological diagnosis of renal osteodystrophy with reference to clinical features in patients undergoing maintenance hemodialysis

    Energy Technology Data Exchange (ETDEWEB)

    Huebsch, P.; Trattnig, S.; Barton, P.; Seidl, G.; Traindl, O.; Kovarik, J.; Wolszczuk, W.

    1989-01-01

    Pathophysiological, histological and radiological findings in renal osteodystrophy are described. Special emphasis is laid on secondary hyperparathyroidism. Preliminary results of the authors' investigations show a good correlation between radiological findings in the phalanges of the hand and the concentration of parathyroid hormone (PTH) in 14 patients. The concentration of the hormone in the blood was measured by a new 'two-site' immunoradiometric assay, which is specific for the intact, biologically active hormone. Patients with high concentrations of PTH in the blood tended to have more severe radiological changes. In 4 patients for whom radiographs of the hands revealed no pathologic findings, normal PTH concentrations in the blood were measured by this method, whereas the conventional assay gave elevated hormone concentrations for the same patients. This is due to the lack of specificity of the conventional method for the intact, biologically active hormone. Nevertheless, further investigations are needed to confirm these findings.

  10. [Hereditary sclerodactyly and syndactyly].

    Science.gov (United States)

    Eubel, R; Klose, L; Mahrle, G

    1985-05-01

    A 61-year-old man is described with sclerodactyly of the hands and syndactyly of the second and third toes. Hereditary sclerodactyly is a rare condition, beginning in early youth with flexion contracture of the fingers. In this patient the skin of the fingers was sclerotic and thickened, and the dorsal skin of the hands was atrophic and dry. The condition did not progress nor did it show signs of Raynaud's phenomenon. Both feet showed syndactyly of the second and third toes. The family tree suggested autosomal dominant inheritance, with reduced penetrance since the grandfather of our patient was reported to have had a similar disease. PMID:2989220

  11. Hereditary angioedema in women

    Directory of Open Access Journals (Sweden)

    Bouillet Laurence

    2010-07-01

    Full Text Available Abstract Women with hereditary angioedema (HAE are more likely to be symptomatic that men. Hormonal factors (puberty, contraception, pregnancy,.... play a significant role in the precipitation or worsening of the condition in women. So, combined contraceptive pills are not indicated and progestogen pill must be preferred. During pregnancy, attack rate can increase (38-48% of women. C1Inhibitor concentrate and tranexamic acid can be used during pregnancy. Attenuated androgens for long term prophylaxis are effective but side effects appear more often in female patients. These side effects are dose dependant and can be attenuated by titrating the dose down the lowest effective level.

  12. Hereditary Hemorrhagic Telangiectasia.

    Science.gov (United States)

    Parambil, Joseph G

    2016-09-01

    Hereditary hemorrhagic telangiectasia (HHT) is an underrecognized and underdiagnosed autosomal-dominant angiodysplasia that has an estimated prevalence of 1 in 5000 individuals, with variable clinical presentations even within family members with identical mutations. The most common manifestations are telangiectasias of the skin and nasal mucosa. However, HHT can often be complicated by the presence of arteriovenous malformations and telangiectasias in the lungs, brain, gastrointestinal tract, and liver that are often silent and can lead to life-threatening complications of stroke and hemorrhage. This article reviews HHT for the pulmonologist, who is not uncommonly the first practitioner to encounter these patients. PMID:27514597

  13. Quantitative and Sensitive Detection of GNAS Mutations Causing McCune-Albright Syndrome with Next Generation Sequencing

    OpenAIRE

    Satoshi Narumi; Kumihiro Matsuo; Tomohiro Ishii; Yusuke Tanahashi; Tomonobu Hasegawa

    2013-01-01

    Somatic activating GNAS mutations cause McCune-Albright syndrome (MAS). Owing to low mutation abundance, mutant-specific enrichment procedures, such as the peptide nucleic acid (PNA) method, are required to detect mutations in peripheral blood. Next generation sequencing (NGS) can analyze millions of PCR amplicons independently, thus it is expected to detect low-abundance GNAS mutations quantitatively. In the present study, we aimed to develop an NGS-based method to detect low-abundance somat...

  14. The Spectrum of Renal Osteodystrophy: A Clinical, Biochemical, Radiological and Histopathological Study

    Directory of Open Access Journals (Sweden)

    Vijay Gupta, Vijay Verma, Rajesh K. Gupta, Dheeraj K. Gandotra, Annil Mahajan, R.K. Saini, V.K. Gupta, V.K. Dubey

    2004-07-01

    Full Text Available The chief mineral source of Jammu province is bauxite, an aluminium ore, so a possibility of waterbeing heavily polluted with aluminium is prevalent. Hence, in an effort to relate this regional geographicalaspect with aluminium bone disease (ABD in chronic renal failure (CRF, 50 cases of CRF wereprospectively evaluated. Patients were subjected to a thorough history and clinical examination.Biochemical parameters along with raiological skeletal survey and iliac crest bone biopsies wereundertaken. Sixty-eight per cent of CRF patients were also consuming aluminium containing phosphatebinders (ACPB at that time. The study revealed an occurrence of ABD in 10% of CRF patients. Itwas found predominantly superimposed upon osteomalacia (8% and mixed osteodystrophy (2%.Superimposed ABD on osteomalacia was found more frequently in pre-dialysis (10.8% than afterhaemodialysis group (7.69%. Moreover, the incidence of ABD superimposed on osteomalacia andmixed osteodystrophy was higher in the ACPB group (14.7% than the post-haemodialysis group(7.69%. Correlating, the pre-dialysis, post-haemodialysis and ACPB ingestion status of CRF patientson one hand and histologically proven ABD on the other, it was deduced that the majority of cases ofCRF having ABD was seen in ACPB ingestion group (14.7% followed by pre-dialysis (10.8% andpost-haemodialysis (7.69% groups. Thus it was concluded that in the present work, ACPB ingestionwas the major source of aluminium deposition in bones of patients with CRF rather than the waterused in dialysis or possible pollution of drinking water with aluminium in our province.

  15. Fulvestrant treatment of precocious puberty in girls with McCune-Albright syndrome

    Directory of Open Access Journals (Sweden)

    Sims Emily K

    2012-09-01

    Full Text Available Abstract Background McCune-Albright Syndrome (MAS is usually characterized by the triad of precocious puberty (PP, fibrous dysplasia, and café au lait spots. Previous treatments investigated for PP have included aromatase inhibitors and the estrogen receptor modulator, tamoxifen. Although some agents have been partially effective, the optimal pharmacologic treatment of PP in girls with MAS has not been identified. The objective of this study was to evaluate the safety and efficacy of fulvestrant (FaslodexTM, a pure estrogen receptor antagonist, in girls with progressive precocious puberty (PP associated with McCune-Albright Syndrome (MAS. Methods In this prospective international multicenter trial, thirty girls ≤ 10 years old with MAS and progressive PP received fulvestrant 4 mg/kg via monthly intramuscular injections for 12 months. Changes in vaginal bleeding, rates of bone age advancement, growth velocity, Tanner staging, predicted adult heights, and uterine and ovarian volumes were measured. Results Median vaginal bleeding days decreased from 12.0 days per year to 1.0 day per year, with a median change in frequency of -3.6 days, (95% confidence interval (CI -10.10, 0.00; p = 0.0146. Of patients with baseline bleeding, 74% experienced a ≥50% reduction in bleeding, and 35% experienced complete cessation during the study period (95% CI 51.6%, 89.8%; 16.4%, 57.3%, respectively. Average rates of bone age advancement (ΔBA/ΔCA decreased from 1.99 pre-treatment to 1.06 on treatment (mean change -0.93, 95% CI -1.43, -0.43; p = 0.0007. No significant changes in uterine volumes or other endpoints or serious adverse events occurred. Conclusions Fulvestrant was well tolerated and moderately effective in decreasing vaginal bleeding and rates of skeletal maturation in girls with MAS. Longer-term studies aimed at further defining potential benefits and risks of this novel therapeutic approach in girls with MAS are needed. Trial

  16. Leber Hereditary Optic Neuropathy

    Directory of Open Access Journals (Sweden)

    Kopishinskaya S.V.

    2014-06-01

    Full Text Available Leber optic neuropathy is mitochondrial neurodegenerative disease manifested by progressive visual deterioration due to optic nerve atrophy. It is most frequently manifested in young people aged from 18 to 30, male patients prevailing. The disease is characterized by maternal inheritance, and the inheritance of a feature discontinues in men. In 95% cases Leber hereditary optic neuropathology is due to one of three known mitochondrial DNA mutations, its type being important in relation to the disease prognosis. The disease course has a number of succeeding stages: preclinical, acute and chronic (atrophic. The disease diagnosis is based on the characteristic clinical presentation of sequential impairment of both eyes forming central scotoma, the analysis of family history and detection of specific mutations. The present clinical observation illustrates the difficulties in Leber disease diagnosis.

  17. Hereditary neuromuscular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Oezsarlak, O. E-mail: ozkan.ozsarlak@uza.be; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J

    2001-12-01

    This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

  18. Hereditary colorectal cancer diagnostics

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge;

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid in...... the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated...

  19. Hereditary angioedema: Not an allergy

    Directory of Open Access Journals (Sweden)

    Sanjay Bhivgade

    2012-01-01

    Full Text Available Hereditary angioedema is a genetic disorder due to a deficiency or malfunction of C1 esterase inhibitor. We herein describe a case of 25-year-old male who presented with swelling over face since one day. There was history of similar episodes since two years with gradual subsidence of swelling without any treatment. Investigations revealed grossly reduced complement C4 and C1 esterase inhibitor level. Patient was diagnosed to have hereditary angioedema type 1 and started on stanozolol 2 mg three times a day with no recurrence in one year of follow-up. Hereditary angioedema resembles angioedema of an allergic reaction. However, the cause is different.

  20. Hereditary Elliptocytosis with Pyropoikilocytosis

    Directory of Open Access Journals (Sweden)

    Turan Bayhan

    2016-03-01

    Full Text Available A 17-day-old boy was admitted because of jaundice and anemia. He was born weighing 2900 g subsequent to a term gestation as the fourth child of first-degree cousin parents. The previous history revealed the administration of phototherapy for 4 days starting from the first day of life. Complete blood count revealed hemoglobin (Hb of 6.9 g/dL, hematocrit of 19.8%, mean corpuscular volume (MCV of 87.5 fL, red cell distribution width (RDW of 37%, white blood cell count of 11.4x109/L, and platelet count of 263x109/L. Corrected reticulocyte count was 5.3%. Peripheral blood smear revealed polychromasia and pyropoikilocytosis. Direct antibody test was negative. Erythrocyte glucose-6-phosphate dehydrogenase, pyruvate kinase, and pyrimidine 5’ nucleotidase levels were normal. An erythrocyte transfusion was administered with a diagnosis of non-immune hemolytic anemia and the patient was discharged at the 26th day of life with initiation of folic acid. During his outpatient followup, he required erythrocyte transfusions 2 more times and the last transfusion was performed when he was 3 months old. At a visit 3 months after the last transfusion, his blood count was as follows: Hb of 9.5 g/dL, hematocrit of 28.2%, MCV of 68.2 fL, and RDW of 30.5%. Erythrocyte osmotic fragility was found to be normal and Hb electrophoresis revealed Hb F of 6.6% and Hb A2 of 1.7%. Upon physical examination he had mild jaundice and no splenomegaly. The parents’ blood counts were within normal ranges. Peripheral blood smear revealed prominent elliptocytes and occasional microcytic and fragmented erythrocytes with poikilocytosis (Figure 1. The clinical findings and laboratory results were diagnostic for the hereditary pyropoikilocytosis (HPP type of hereditary elliptocytosis (HE, but in vitro fragmentation testing was not performed

  1. A Case of Atypical McCune-Albright Syndrome with Vaginal Bleeding

    Directory of Open Access Journals (Sweden)

    Silva Hovsepian

    2011-09-01

    Full Text Available Background:McCune-Albright syndrome (MAS is a rare non-inherited disorder characterized by the clinical triad of precocious puberty, cafe-au-lait skin lesions, and fibrous dysplasia of bone. Case Presentation:We report a girl with MAS, presenting initially with vaginal bleeding at the age of 17 months. Ultrasonography revealed unilateral ovarian cysts and ureteral and ovarian enlargement. Considering the clinical and paraclinical findings, the patient diagnosed as a case of gonadotropin-independent precocious puberty was treated with medroxy-progestrone acetate (MPA for three months. During the follow up, recurrent episodes of bleeding, ovarian activation and cyst formation, as well as breast size development were reported. At the age of 5.5 years, fibrous dysplasia was detected, which in coexistence with precocious puberty confirmed the diagnosis of MAS. The patient had no cafe-au-lait skin macles during follow up. Conclusion:Considering that clinical manifestations of MAS appear later in the course of recurrent periods of ovarian activation and cyst formation, a careful clinical observation and follow up of patients is necessary and the diagnosis of MAS must be kept in mind in cases with gonadotropin-independent precocious puberty.

  2. [Pubertas praecox in McCune-Albright syndrome--case report and review of the literature].

    Science.gov (United States)

    Stier, B; Ranke, M B

    1987-01-01

    A patient is presented with the syndrome of polyostatic fibrous dysplasia and precocious puberty (PP). The endocrinopathy in McCune-Albright-syndrome (MAS) has formerly been ascribed to a central (hypothalamic) origin. In this patient the PP was caused by a luteinized follicular cyst, suggesting autonomous hyperfunction of this gland. High serum estradiol levels returned to normal after cystectomie. The review of the literature suggests the peripheral origin of PP to be more frequent in younger age groups (under 6 years). It appears possible that peripheral hypersecretion of sexual steroids may cause a rise of gonadotropins secondarily followed by true PP in older children provided such longstanding hypersecretion leads to a generalized maturation of the body including skeletal maturation. Treatment in pseudoprecocious puberty seems to be not effective with LH-RH-analogues. Cyproteroneacetate alone or in combination with a LH-RH analogue gave the impression of being more successful. Cystectomy can lead to a cure but a recurrence of ovarian cysts is possible. A combination of surgical and drug therapy may be beneficial under these circumstances. Until now there is no sufficient treatment for polyostotic fibrous dysplasia. PMID:3316827

  3. Hereditary iron and copper deposition

    DEFF Research Database (Denmark)

    Aaseth, Jan; Flaten, Trond Peder; Andersen, Ole

    2007-01-01

    Hereditary deposition of iron (primary haemochromatosis) or copper (Wilson's disease) are autosomal recessive metabolic disease characterized by progressive liver pathology and subsequent involvement of various other organs. The prevalence of primary haemochromatosis is approximately 0.5%, about...

  4. Gene Testing for Hereditary Ataxia

    Science.gov (United States)

    FAQ NATIONAL ATAXIA FOUNDATION FREQUENTLY ASKED QUESTIONS ABOUT... Gene Testing for Hereditary Ataxia This fact sheet provides an overview of gene testing for ataxia. It also addresses commonly asked ...

  5. DESIGNING AN OPPORTUNITY FUEL WITH BIOMASS AND TIRE-DERIVED FUEL FOR COFIRING AT WILLOW ISLAND GENERATING STATION AND COFIRING SAWDUST WITH COAL AT ALBRIGHT GENERATING STATION

    International Nuclear Information System (INIS)

    During the period July 1, 2001-September 30, 2001, Allegheny Energy Supply Co., LLC (Allegheny) continued construction of the Willow Island cofiring project, completed the installation of the fuel storage facility, the fuel receiving facility, and the processing building. All mechanical equipment has been installed and electrical construction has proceeded. During this time period significant short term testing of the Albright Generating Station cofiring facility was completed, and the 100-hour test was planned for early October. The testing demonstrated that cofiring at the Albright Generating Station could contribute to a ''4P Strategy''-reduction of SO(sub 2), NO(sub x), mercury, and greenhouse gas emissions. This report summarizes the activities associated with the Designer Opportunity Fuel program, and demonstrations at Willow Island and Albright Generating Stations. It details the construction activities at both sites along with the combustion modeling at the Willow Island site

  6. Adult hereditary fructose intolerance

    Institute of Scientific and Technical Information of China (English)

    Mohamed Ismail Yasawy; Ulrich Richard Folsch; Wolfgang Eckhard Schmidt; Michael Schwend

    2009-01-01

    Hereditary fructose intolerance (HFI) is an underrecognized,preventable life-threatening condition. It is an autosomal recessive disorder with subnormal activity of aldolase B in the liver, kidney and small bowel. Symptoms are present only after the ingestion of fructose, which leads to brisk hypoglycemia, and an individual with continued ingestion will exhibit vomiting,abdominal pain, failure to thrive, and renal and liver failure. A diagnosis of HFI was made in a 50-year-old woman on the basis of medical history, response to Ⅳ fructose intolerance test, demonstration of aldolase B activity reduction in duodenal biopsy, and molecular analysis of leukocyte DNA by PCR showed homozygosity for two doses of mutant gene. HFI may remain undiagnosed until adult life and may lead to disastrous complications following inadvertent fructose or sorbitol infusion. Several lethal episodes of HFI following sorbitol and fructose infusion have been reported. The diagnosis can only be suspected by taking a careful dietary history, and this can present serious complications.

  7. Icatibant for hereditary angioedema.

    Science.gov (United States)

    Gras, Jordi

    2009-12-01

    Hereditary angioedema (HAE) is an autosomal dominant, potentially life-threatening disease, characterized by recurrent self-limiting bouts of edema mainly involving the extremities, genitalia, face, intestines and airways. The prevalence of HAE in the general population has been estimated to be in the range of 1:10,000 to 1:150,000. Currently, acute attacks of HAE are treated mainly symptomatically, with poor outcomes. Recently, it has been demonstrated that bradykinin (BK) is responsible for most of the symptoms of HAE. Icatibant (Firazyr, HOE 140, JE049) is a potent, specific and selective B2 BK receptor antagonist that has recently been approved by the EMEA for the treatment of HAE. In phase III clinical trials, 30 mg of subcutaneous icatibant demonstrated rapid and stable relief from symptoms in cutaneous, abdominal or laryngeal HAE attacks. Local site reactions after subcutaneous injection of icatibant were observed, however, these reactions were mild to moderate in severity and resolved spontaneously and quickly. Icatibant is a new, safe and effective treatment for acute attacks of HAE. PMID:20135020

  8. Study on renal osteodystrophy using 2-compartment model analysis of bone scintigraphy, 1

    International Nuclear Information System (INIS)

    The dynamic analyses of bone scintigraphy were performed in 30 cases of hemodialysed patients. The regression analyses between biochemical data or duration and K indexes obtained from the 2-compartment model analysis in the maxillofacial region were carried out. The obtained results were as follows. The duration and K indexes were significantly correlated with 1 or 2% of significance level in the parietal bone and the zygomatic bone. Serum Ca K indexes were highly correlated in every settled ROI. The correlation coefficients were distributed from 0.58 to 0.79. In the cranial bone the correlation were more higher than in maxilla and mandibular bone. Serum ALP and K indexes have more higher significant level of correlation than the results of Ca. The correlation coefficients were distributed from 0.48 to 0.83. The level of significance were changed by location. The highest correlation coefficient was 0.83 in the parietal bone. Serum C-PTH and K indexes have significant correlation in every settled ROI with the correlation coefficient from 0.59 to 0.69. The significance level were nearly equal in every location. In the case of subtotal parathyroidoectomy the K indexes which were abnormally high in preoperation showed the tendancy to decrease toward normal range in postoperation. These results indicated that K indexes reflected the bone change caused by renal osteodystrophy. And the K indexes considered to be useful to estimate the bone improvement. (author)

  9. Studies of the skeletal pathophysiology of renal osteodystrophy using nucleomedical procedures

    International Nuclear Information System (INIS)

    Bone scintigraphy with Tc-99m labeled phosphorous compounds has been performed in a series of 160 long-term hemodialysis patients with chronic renal failure. Renal osteodystrophy (ROD) was classified by five features of RI uptake in the entire skeleton: type A (low turn-over type) - a relatively decreased RI uptake in the bone tissue and an increased uptake in the soft tissue; type C (normal type) - normal findings; type D (osteomalacia type) - a strong RI uptake in the costochondral joints; type F (hyperparathyroid type) - strong RI uptake in the skull and submandible; and type G (calcification type) - an ectopic calcification. The group of type F had elevated levels of both alkaline phosphatase (ALP) and parathyroid hormones (PTH); on the contrary, both ALP and PTH were decreased in the group of type A. This suggested an increased and decreased bone metabolism in type F and A, respectively. The group of type D was characterized by having hypophosphatemia. Pathophysiologic types of ROD varied from day to day. Bone mineral density (BMD) tended to decrease in the radius. For the spine, however, BMD increased in some cases and decreased in the other cases with prolonging the duration of hemodialysis. Bone scintigraphy and BMD determination in both the cortical and cavernous bone tissue may provide integrated information about ROD presenting with heterogeneity of the entire skeleton. (Namekawa, K)

  10. Differences in Bone Quality between High versus Low Turnover Renal Osteodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Porter, Daniel S. [University of Kentucky, Lexington; Pienkowski, David [University of Kentucky, Lexington; Faugere, Marie-Claude [Albert B. Chandler Medical Center; Malluche, Hartmut H. [Albert B. Chandler Medical Center

    2012-01-01

    Abnormal bone turnover is common in chronic kidney disease (CKD), but its effects on bone quality remain unclear. This study sought to quantify the relationship between abnormal bone turnover and bone quality. Iliac crest bone biopsies were obtained from CKD-5 patients on dialysis with low (n=18) or high (n=17) turnover, and from volunteers (n=12) with normal turnover and normal kidney function. Histomorphometric methods were used to quantify the microstructural parameters; Fourier transform infrared spectroscopy and nanoindentation were used to quantify the material and mechanical properties in bone. Reduced mineral-to-matrix ratio, mineral crystal size, stiffness and hardness were observed in bone with high turnover compared to bone with normal or low turnover. Decreased cancellous bone volume and trabecular thickness were seen in bone with low turnover compared to bone with normal or high turnover. Bone quality, as defined by its microstructural, material, and mechanical properties, is related to bone turnover. These data suggest that turnover related alterations in bone quality may contribute to the known diminished mechanical competence of bone in CKD patients, albeit from different mechanisms for bone with high (material abnormality) vs. low (microstructural alteration) turnover. The present findings suggest that improved treatments for renal osteodystrophy should seek to avoid low or high bone turnover and aim for turnover rates as close to normal as possible.

  11. Applicability of Fractal Dimension Analysis in Dental Radiographs for the Evaluation of Renal Osteodystrophy

    Science.gov (United States)

    Fernandes, Maurício Anderson; Ribeiro Rosa, Edvaldo Antônio; Johann, Aline Cristina Batista Rodrigues; Grégio, Ana Maria Trindade; Trevilatto, Paula Cristina; Azevedo-Alanis, Luciana Reis

    2016-01-01

    Objectives: To test the capacity of the digital tool, fractal dimension (FD) analysis, in identifying subtle differences in bone pattern in patients with renal osteodystrophy (RO), correlated with the time of hemodialysis, in different regions of interest, delineated on panoramic and periapical radiographs. Study design: A total of 34 patients with chronic renal disease undergoing hemodialysis were submitted to panoramic and periapical radiographs. Different regions of interest were delineated on the mandibular body and ramus. FD was analyzed by means of the software program ImageJ and correlated with the time of hemodialysis. Results: The sample consisted of 34 subjects. The time of hemodialysis varied from 1 to 286 months. There was significant correlation between the time of hemodialysis and the FD values in the region delineated in the mandibular angle (r = 0.498; p = 0.003) and this was shown in the periapical radiographs as well (r = -0.349; p = 0.043). Conclusions: FD analysis was a useful tool in detecting alterations caused by RO in bone pattern, in panoramic and periapical radiographs.

  12. Bone scan appearance of renal osteodystrophy in diabetic chronic renal failure patients

    International Nuclear Information System (INIS)

    To investigate Tc-99m methylenediphosphonate (MDP) bone scan appearance in diabetic chronic renal failure patients, we compared the bone scan images of chronic renal failure patients with and without diabetes. The number of patients studied was 134, of whom 43 had diabetes. Two nuclear medicine physicians read Tc-99m MDP bone scan images and for six areas - the axial skeleton, long bone, skull and mandible, periarticular areas, costochondral junction, and sternum - assigned a score of either 1 or 0. The sums of scores were compared. We also performed multivariate analysis including sex, age, and serum creatinine level using analysis of covariance. DM group patients scored significantly lower (2.01±0.95) than those of the non-DM group (3.26±1.16). Analysis of covariance revealed that the lower DM group score was independent of sex, age, and serum creatinine level. The bone scans of diabetic chronic renal failure patients showed less Tc-99m MDP uptake than those of non-diabetic patients. Thus, diagnosing renal osteodystrophy in diabetic chronic renal failure patients on bone scan images could be difficult. (author)

  13. Hereditary Hemorrhagic Telangiectasia (HHT) and Pulmonary Hypertension

    Science.gov (United States)

    Hereditary Hemorrhagic Telangiectasia (HHT) Pulmonary & PH Hypertension Did you know that if you have HHT, you are at risk for pulmonary ... options for patients in the future. Hereditary Hemorrhagic Telangiectasia-Associated PH, or HHT-Associated PH My doctor ...

  14. Genetics Home Reference: hereditary hemorrhagic telangiectasia

    Science.gov (United States)

    ... Changes Mutations in several genes, including the ACVRL1 , ENG , and SMAD4 genes, cause hereditary hemorrhagic telangiectasia . Hereditary ... type 1 is caused by mutations in the ENG gene. Type 2 is caused by mutations in ...

  15. The relevance of mineralization lag time in the evaluation of histologic changes in renal osteodystrophy.

    Science.gov (United States)

    Libbey, N P; Chazan, J A; London, M R; Pono, L; Abuelo, J G

    1993-04-01

    We examined bone biopsies from 47 patients on chronic hemodialysis, and analyzed the histomorphometric and biochemical findings and histologic quantitation of bone aluminium, looking primarily at mineralization lag time (Mlt) to evaluate its usefulness in categorization of renal osteodystrophy (ROD). The patients were categorized as having either relatively normal Mlt ( 100 days, n = 13 patients). The group with relatively normal Mlt showed significantly higher C-terminal parathyroid hormone (PTHc) levels (26,141 +/- 19,270 vs 7,226 +/- 6,073 and 4,434 +/- 4,000 pg/ml) than the moderately or markedly prolonged Mlt groups (p < .01) and was associated with histologic characteristics of osteitis fibrosa or mild hyperparathyroidism (BFR/BS range 0.146-0.947 mcm3/mcm2/d). The group with markedly prolonged Mlt included one patient with classic and 11 with adynamic osteomalacia (BFR/BS range 0.009-0.099) and had greater bone aluminum (Al.S/OS 35.3 +/- 26.7% vs 7.2 +/- 9.0%) than the normal Mlt group (p < .01). The group with moderately prolonged Mlt included two patients with aplastic bone disease (Mlt 80.0 and 84.6 days, and Al.S/OS 100.0 and 72.3%) and 11 patients with features of hyperparathyroidism and osteomalacia (BFR/BS range 0.068-0.243) with variable but generally intermediate bone aluminum deposition (Al.S/OS 22.5 +/- 19.9%). Like BFR/BS and other dynamic parameters Mlt correlates with morphologic types of ROD which primarily reflect bone turnover, but it may also suggest varying degrees of mineralization impairment in a spectrum ranging from high to low turnover types of ROD. Its usefulness in this respect should not be overlooked. PMID:8491052

  16. Neue radiologische und serologische Methoden zur Diagnose der renalen Osteodystrophie bei Dialysepatienten

    Directory of Open Access Journals (Sweden)

    Cejka D

    2014-01-01

    Full Text Available Mit Abnahme der Nierenfunktion steigt die Prävalenz der renalen Osteodystrophie (ROD, im Dialysestadium ist fast jeder Patient von ROD betroffen. Dialysepatienten haben verglichen mit der Normalbevölkerung ein 4-fach erhöhtes Risiko, eine Oberschenkelhalsfraktur zu erleiden. Die ROD ist eine Urämie-bedingte Erkrankung des Knochens, die zu Veränderungen des Knochenstoffwechsels („turnover“ [T], der Mineralisierung („mineralization“ [M] und des Knochenvolumens („volume“ [V] führen kann. Bislang ist die Untersuchung all dieser Veränderungen nur mittels invasiver Knochenbiopsie mit anschließender Histomorphometrie und TMV-Klassifizierung möglich. Klinisch verfügbare Methoden wie Knochendichtemessung („dual-energy X-ray absorptiometry“ [DXA] oder Bestimmung von Parathormon beziehungsweise von Knochenstoffwechselparametern zeigen niedrige Sensitivitäten/Spezifitäten bezüglich der korrekten Klassifizierung der ROD. Unter den neuen radiologischen Methoden erscheint die „high-resolution peripheral quantitative computed tomography“ (HR-pQCT eine vielversprechende Methode. In einer Studie war die HR-pQCT der konventionellen DXA bezüglich der Unterscheidung zwischen Dialysepatienten mit und ohne Vorgeschichte einer Low-trauma-Fraktur deutlich überlegen. Unter den neu entdeckten Knochenstoffwechselmarkern hat die Messung von Sclerostin einen hohen Vorhersagewert für das Vorliegen einer „highturnover bone disease“ gezeigt. Diesen interessanten Ansätzen zum Trotz bedarf es weiterer Forschung auf dem Gebiet. Insbesondere gibt es bislang keine Methode, die mit hoher Sicherheit Low-impact-Frakturen bei Dialysepatienten vorhersagen kann.

  17. Nutritional education for management of osteodystrophy: Impact on serum phosphorus, quality of life, and malnutrition.

    Science.gov (United States)

    Karavetian, Mirey; Elzein, Hafez; Rizk, Rana; Jibai, Rime; de Vries, Nanne

    2016-07-01

    Introduction Osteodystrophy management includes dietary phosphorus restriction, which may limit protein intake, exacerbate malnutrition-inflammation syndrome and mortality among hemodialysis patients. Methods A multicenter randomized controlled trial was conducted in Lebanon, to test the hypothesis that intensive nutrition education focused on phosphorus-to-protein balance will improve patient outcomes. Six hemodialysis units were randomly assigned to the trained hospital dietitian (THD) protocol (210 patients). Six others (184 patients) were divided equally according to the patients' dialysis shifts and assigned to Dedicated Dietitian (DD) and Control protocols. Patients in the THD group received nutrition education from hospital dietitians who were trained by the study team on renal dietetics, but had limited time for hemodialysis patients. Patients in the DD group received individualized nutritional education on dietary phosphorus and protein management for 6 months (2-hour/patient/month) from study renal dietitians. Patients in the control group continued receiving routine care from hospital dietitians who had limited time for these patients and were blinded to the study. Serum phosphorus (mmol/L), malnutrition-inflammation score (MIS), health-related quality of life (HRQOL) index and length of hospital stay (LOS) were assessed at T0 (baseline), T1 (postintervention) and T2 (post6 month follow up). Findings Only the DD protocol significantly improved serum phosphorus (T0:1.78 ± 0.5, T1:1.63 ± 0.46, T2:1.69 ± 0.53), 3 domains of the HRQOL and maintained MIS at T1, but this protective effect resolved at T2. The LOS significantly dropped for all groups. Discussion The presence of competent renal dietitians fully dedicated to hemodialysis units was superior over the other protocols in temporarily improving patient outcomes. PMID:26843138

  18. Gsα Deficiency in Adipose Tissue Leads to a Lean Phenotype with Divergent Effects on Cold Tolerance and Diet-Induced Thermogenesis

    OpenAIRE

    Chen, Min; Chen, Hui; Nguyen, Annie; Gupta, Divakar; Jie WANG; Lai, Edwin W.; Pacak, Karel; Gavrilova, Oksana; Michael J Quon; Weinstein, Lee S.

    2010-01-01

    Gsα, the G protein which mediates receptor-stimulated cAMP generation, has been implicated as a regulator of adipogenesis and adipose tissue function. Heterozygous Gsα mutations lead to obesity in Albright hereditary osteodystrophy (AHO) patients and in mice. In this study we generated mice with adipose-specific Gsα deficiency. Heterozygotes had 50% loss of Gsα expression in adipose tissue and no obvious phenotype, suggesting that adipose-specific Gsα deficiency is not the cause of obesity in...

  19. Socioeconomic burden of hereditary angioedema

    DEFF Research Database (Denmark)

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen;

    2014-01-01

    BACKGROUND: Hereditary angioedema (HAE) due to C1 inhibitor deficiency is a rare but serious and potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The study objective was to characterize direct and indirect resource utilization associated with HAE from the...

  20. Fibrous dysplasia and McCune–Albright syndrome: Imaging for positive and differential diagnoses, prognosis, and follow-up guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Bousson, Valérie, E-mail: valerie.bousson@lrb.aphp.fr [Radiologie Ostéo-Articulaire, AP-HP, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010 Paris (France); Université Paris VII Denis Diderot, Sorbonne Paris Cité (France); Rey-Jouvin, Caroline, E-mail: c.reyjouvin@gmail.com [Rhumatologie Viggo Petersen, AP-HP, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010 Paris (France); Université Paris VII Denis Diderot, Sorbonne Paris Cité (France); Laredo, Jean-Denis, E-mail: jean-denis.laredo@lrb.aphp.fr [Radiologie Ostéo-Articulaire, AP-HP, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010 Paris (France); Université Paris VII Denis Diderot, Sorbonne Paris Cité (France); Le Merrer, Martine, E-mail: martine.lemerrer@inserm.fr [Service de génétique médicale, AP-HP, Hôpital Necker – Enfants malades, 149 rue de Sèvres, 75743 Paris Cedex 15 (France); Martin-Duverneuil, Nadine, E-mail: nadine.martin-duverneuil@psl.aphp.fr [Service de Neuroradiologie, AP-HP, Hôpital Pitié Salpêtrière, 47 Boulevard de l’hôpital, 75013 Paris (France); and others

    2014-10-15

    Highlights: • The radiologist plays a critical role at all steps of the management of patients with fibrous dysplasia (FD) and McCune–Albright syndrome (MAS). • Specific recommendations are provided as key points for the diagnosis, prognosis, and follow-up of patients with FD/MAS. • We believe the dissemination of these recommendations within the radiology community may substantially improve the management of patients with these rare but potentially disabling conditions. - Abstract: Purpose: The radiologist plays a critical role at all steps of the management of patients with fibrous dysplasia (FD) and McCune–Albright syndrome (MAS). The development of a standardized approach to the management of FD/MAS is crucial given the low incidence and multiple clinical presentations of these conditions. Our aim was to develop recommendations for bone imaging in FD/MAS management. Materials and methods: The establishment of National Reference Centers in France as part of a Health Ministry program for orphan diseases has triggered the development of recommendations for the clinical management of FD/MAS. We used a well-established robust methodological approach involving an extensive literature review by a multidisciplinary working group (20 healthcare professionals) and scoring by a peer-review group (20 healthcare professionals different from the 20 previous ones). There were four phases: a systematic literature review, drafting of initial recommendations, peer-review of this initial draft, and drafting of the final recommendations. Results: Fifty-seven specific recommendations are provided as key points for the diagnosis, prognosis, and follow-up of patients with FD/MAS. Issues of special interest are highlighted in the discussion, and areas in which future research is needed are identified. Conclusion: We believe the dissemination of these recommendations within the radiology community may facilitate communication between radiologists and other healthcare

  1. Fibrous dysplasia and McCune–Albright syndrome: Imaging for positive and differential diagnoses, prognosis, and follow-up guidelines

    International Nuclear Information System (INIS)

    Highlights: • The radiologist plays a critical role at all steps of the management of patients with fibrous dysplasia (FD) and McCune–Albright syndrome (MAS). • Specific recommendations are provided as key points for the diagnosis, prognosis, and follow-up of patients with FD/MAS. • We believe the dissemination of these recommendations within the radiology community may substantially improve the management of patients with these rare but potentially disabling conditions. - Abstract: Purpose: The radiologist plays a critical role at all steps of the management of patients with fibrous dysplasia (FD) and McCune–Albright syndrome (MAS). The development of a standardized approach to the management of FD/MAS is crucial given the low incidence and multiple clinical presentations of these conditions. Our aim was to develop recommendations for bone imaging in FD/MAS management. Materials and methods: The establishment of National Reference Centers in France as part of a Health Ministry program for orphan diseases has triggered the development of recommendations for the clinical management of FD/MAS. We used a well-established robust methodological approach involving an extensive literature review by a multidisciplinary working group (20 healthcare professionals) and scoring by a peer-review group (20 healthcare professionals different from the 20 previous ones). There were four phases: a systematic literature review, drafting of initial recommendations, peer-review of this initial draft, and drafting of the final recommendations. Results: Fifty-seven specific recommendations are provided as key points for the diagnosis, prognosis, and follow-up of patients with FD/MAS. Issues of special interest are highlighted in the discussion, and areas in which future research is needed are identified. Conclusion: We believe the dissemination of these recommendations within the radiology community may facilitate communication between radiologists and other healthcare

  2. New treatments of hereditary blindness

    DEFF Research Database (Denmark)

    Bertelsen, Mette; Rosenberg, Thomas; Larsen, Michael

    2013-01-01

    Ongoing clinical trials are targeting several previously intractable hereditary causes of blindness of congenital, childhood or early adulthood onset, mainly in the optic nerve and retina. The intended stage of initiation of the new therapeutic approaches ranges from neonatal life and a structura......Ongoing clinical trials are targeting several previously intractable hereditary causes of blindness of congenital, childhood or early adulthood onset, mainly in the optic nerve and retina. The intended stage of initiation of the new therapeutic approaches ranges from neonatal life and a...... structurally intact retinal tissue to adult life with a complete loss of photoreceptors. It must be assumed that some of the trials will succeed in producing new therapies and action must be taken to refine and accelerate diagnostics and to preserve therapeutic potential in blind people....

  3. Hereditary Methemoglobinemia: A Case Report

    OpenAIRE

    T Bostan; MT Haghi Ashtiani; A. Khodadad

    1995-01-01

    An 11-year old girl is presented by whom a generalized cyanosis since birth was noticed and hereditary Methemoglobinemia diagnosed when she was 3 years old. She is treated successfully with daily oral vitamin C administration. After 8 years of treatment she shows normal physical and mental development. It is recommended to use screening test for Methemoglobinemia by all cyanotic children, which is simple and specific.

  4. Hereditary progressive chorea without dementia.

    OpenAIRE

    Schady, W; Meara, R J

    1988-01-01

    A family with hereditary non-Huntington's chorea is presented. Transmission was autosomal dominant with variable penetrance. Chorea commenced in childhood and affected predominantly the head, face and upper limbs. Dysarthria appeared later, followed in two family members by elements of an axial dystonia. There was no intellectual impairment. Unlike previously described families, symptoms progressed steadily up to the eighth decade, causing considerable physical disability.

  5. Monilethrix: A rare hereditary condition

    Directory of Open Access Journals (Sweden)

    Adaikalampillai Ganapathy Vikramkumar

    2013-01-01

    Full Text Available Monilethrix is a rare hereditary condition generally considered to be an autosomal-dominant disorder with variable penetrance. Here, we report a case of monilethrix in a 13-year-old boy with an affected sibling. A therapeutic trial with oral N-acetyl cysteine was attempted. There was slight improvement after 2 months of therapy. The hair density, however, did not show any further improvement subsequently. Monilethrix remains as a therapeutic challenge for dermatologists.

  6. Management of hereditary angioedema in pediatric patients.

    Science.gov (United States)

    Farkas, Henriette; Varga, Lilian; Széplaki, Gábor; Visy, Beáta; Harmat, George; Bowen, Tom

    2007-09-01

    Hereditary angioneurotic edema is a rare disorder caused by the congenital deficiency of C1 inhibitor. Recurring angioedematous paroxysms that most commonly involve the subcutis (eg, extremities, face, trunk, and genitals) or the submucosa (eg, intestines and larynx) are the hallmarks of hereditary angioneurotic edema. Edema formation is related to reduction or dysfunction of C1 inhibitor, and conventional therapy with antihistamines and corticosteroids is ineffective. Manifestations occur during the initial 2 decades of life, but even today there is a long delay between the onset of initial symptoms and the diagnosis of hereditary angioneurotic edema. Although a variety of reviews have been published during the last 3 decades on the general management of hereditary angioneurotic edema, little has been published regarding management of pediatric hereditary angioneurotic edema. Thus, we review our experience and published data to provide an approach to hereditary angioneurotic edema in childhood. PMID:17724112

  7. On Hereditary Helly classes of graphs

    Directory of Open Access Journals (Sweden)

    Marina Groshaus

    2008-01-01

    Full Text Available In graph theory, the Helly property has been applied to families of sets, such as cliques, disks, bicliques, and neighbourhoods, leading to the classes of clique-Helly, disk-Helly, biclique-Helly, neighbourhood-Helly graphs, respectively. A natural question is to determine for which graphs the corresponding Helly property holds, for every induced subgraph. This leads to the corresponding classes of hereditary clique-Helly, hereditary disk-Helly, hereditary biclique-Helly and hereditary neighbourhood-Helly graphs. In this paper, we describe characterizations in terms of families of forbidden subgraphs, for the classes of hereditary biclique-Helly and hereditary neighbourhood-Helly graphs. We consider both open and closed neighbourhoods. The forbidden subgraphs are all of fixed size, implying polynomial time recognition for these classes.

  8. On hereditary Helly classes of graphs

    OpenAIRE

    Marina Groshaus; Jayme Luiz Szwarcfiter

    2008-01-01

    In graph theory, the Helly property has been applied to families of sets, such as cliques, disks, bicliques, and neighbourhoods, leading to the classes of clique-Helly, disk-Helly, biclique-Helly, neighbourhood-Helly graphs, respectively. A natural question is to determine for which graphs the corresponding Helly property holds, for every induced subgraph. This leads to the corresponding classes of hereditary clique-Helly, hereditary disk-Helly, hereditary biclique-Helly and hereditar...

  9. Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema

    Science.gov (United States)

    Andersen, Michelle Fog; Bygum, Anette

    2015-01-01

    Hereditary angioedema is a rare, but potentially life-threatening genetic disorder that results from an autosomal dominant trait. It is characterized by acute, recurrent attacks of severe local edema, most commonly affecting the skin and mucosa. Swelling in hereditary angioedema patients does however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack of hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting. PMID:26819784

  10. Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema

    DEFF Research Database (Denmark)

    Andersen, Michelle Fog; Bygum, Anette

    2015-01-01

    Hereditary angioedema is a rare, but potentially life-threatening genetic disorder that results from an autosomal dominant trait. It is characterized by acute, recurrent attacks of severe local edema, most commonly affecting the skin and mucosa. Swelling in hereditary angioedema patients does...... however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack of...... hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting....

  11. Genetics Home Reference: hereditary neuralgic amyotrophy

    Science.gov (United States)

    ... Peripheral Neuropathy Fact Sheet Educational Resources (6 links) Disease InfoSearch: Hereditary neuralgic amyotrophy Dutch Neuromuscular Research Centre JAMA Patient Page: Peripheral Neuropathy ...

  12. Genetics Home Reference: hereditary sensory neuropathy type IA

    Science.gov (United States)

    ... Health Conditions hereditary sensory neuropathy type IA hereditary sensory neuropathy type IA Enable Javascript to view the ... Download PDF Open All Close All Description Hereditary sensory neuropathy type IA is a condition characterized by ...

  13. The clinical spectrum of renal osteodystrophy in 57 chronic hemodialysis patients: a correlation between biochemical parameters and bone pathology findings.

    Science.gov (United States)

    Chazan, J A; Libbey, N P; London, M R; Pono, L; Abuelo, J G

    1991-02-01

    Fifty-nine chronic hemodialysis patients who had been on dialysis for an average of 77 months underwent bone biopsies and the pathologic findings were correlated with biochemical and demographic data. All but two had evidence of renal osteodystrophy, 23 with osteitis fibrosa (OF), 19 with osteomalacia and/or adynamic disease (OM/AD), and 15 with mixed osteodystrophy (MOD). Patients in each group were similar with regard to age, sex distribution, duration of dialysis, unstimulated serum aluminum, calcium and phosphorus. Patients with osteitis fibrosa (OF) had statistically higher DFO stimulated aluminum, alkaline phosphatase and PTHC levels than the other two groups although there was marked individual variation. The bone biopsies were also evaluated for the amount of aluminum deposited in the osteoid seam. All 23 of the patients with OF and 11 of the 15 patients with MOD had no, mild, or minimal aluminum deposition but 12 of the 19 patients with OM/AD had moderate to marked aluminum deposition. Patients with minimal to mild aluminum deposition were similar in age, duration of dialysis, sex distribution, unstimulated and DFO stimulated aluminum levels, calcium, phosphorus, alkaline phosphatase to those with moderate to marked deposition but had significantly higher parathormone levels. All patients had been treated in a similar fashion regarding diet, oral phosphate binders and vitamin D; therefore, the observed differences in bone pathology were not readily explicable. However, patients who were found to have osteitis fibrosa and those with minimal to mild aluminum deposition had significantly higher parathormone levels when compared with patients in the other groups at the inception of dialysis. PMID:2019018

  14. Molecular pathogenesis of hereditary hemochromatosis.

    Science.gov (United States)

    Liu, Jingqi; Pu, Chunwen; Lang, Lang; Qiao, Liang; Abdullahi, Mohanud Abukar Haji; Jiang, Chunmeng

    2016-08-01

    Hereditary hemochromatosis (HH) is an inherited iron overload disorder characterized by normal iron-driven erythropoiesis and abnormal iron metabolism, leading to excess iron deposited in parenchymal cells of liver, heart, and endocrine glands. Iron hormone, hepcidin, plays a critical role in iron homeostasis through interaction with ferroportin (FPN), a major cellular iron exporter. Hepcidin is encoded by hepcidin antimicrobial peptide (HAMP). Mutations in hepcidin and any genes that regulate the biology of hepcidin, including hemochromatosis genes (HFE), Hemojuvelin (HJV), transferring receptor 2 (TFR2) and FPN, result in hemochromatosis. The identification of hepcidin and its role will provide a better understanding for pathogenesis of HH. PMID:27031690

  15. Factorization Norms and Hereditary Discrepancy

    OpenAIRE

    Matousek, Jiri; Nikolov, Aleksandar; Talwar, Kunal

    2014-01-01

    The $\\gamma_2$ norm of a real $m\\times n$ matrix $A$ is the minimum number $t$ such that the column vectors of $A$ are contained in a $0$-centered ellipsoid $E\\subseteq\\mathbb{R}^m$ which in turn is contained in the hypercube $[-t, t]^m$. We prove that this classical quantity approximates the \\emph{hereditary discrepancy} $\\mathrm{herdisc}\\ A$ as follows: $\\gamma_2(A) = {O(\\log m)}\\cdot \\mathrm{herdisc}\\ A$ and $\\mathrm{herdisc}\\ A = O(\\sqrt{\\log m}\\,)\\cdot\\gamma_2(A) $. Since $\\gamma_2$ is p...

  16. Two cases of hereditary fructose intolerance

    OpenAIRE

    Ananth, N; Praveenkumar, G. S.; Rao, K Aravind; Vasanthi; Kakkilaya, Srinivas

    2003-01-01

    Hereditary fructose intolerance is a rare cause of hepatic cirrhosis in the young. The disorder has a reported frequency of 1 in 20000 live births and no case has been reported from India so far. We report two cases of hereditary fructose intolerance, both with bilateral cataracts and one with cirrhosis of the liver.

  17. [Hereditary angioneurotic edema in children].

    Science.gov (United States)

    Farkas, H; Harmat, G; Füst, G; Varga, L; Visy, B

    2000-11-19

    Hereditary angioneurotic edema results from the deficiency of C1-esterase inhibitor. The clinical picture of this autosomal dominant disorder is characterized by recurrent attacks of edema formation in the subcutis and/or the submucosa. The clinical records of 21 children with established hereditary angioneurotic edema were reviewed. Follow-up care included laboratory check-ups and abdominal ultrasound. Clinical manifestations of the disease first occurred in 2.5 to 12 years of age. Mechanical trauma was the most common precipitating factor. Pedigree-analysis revealed 19 patients with afflicted relatives. Long-term prophylaxis was initiated with tranexamic acid and danazol in 10 cases; 2 children required short-term prophylaxis. Therapy improved serum complement parameters significantly and reduced the frequency and severity of clinical manifestations. Acute, life-threatening edematous attacks were treated by the administration of C1-inhibitor concentrate, which achieved the resolution of the edema within several hours. Abdominal ultrasonography performed during the attack invariably demonstrated transitory ascites that resolved spontaneously after treatment. Adequate prophylaxis and follow-up care can spare pediatric patients from edematous attacks. Undesirable adverse effects can be avoided and the patient's quality of life can be enhanced considerably by administering the lowest effective drug dose. PMID:11143287

  18. Two cases of pseudohypoparathyroidism type ia in duozygotic twins with different phenotypes.

    Science.gov (United States)

    Nagasaki, Keisuke; Shimomura, Yutaka; Suyama, Takayuki; Magara, Shinichi; Ogawa, Yohei; Hiura, Makoto; Kikuchi, Toru; Uchiyama, Makoto

    2005-01-01

    Pseudohypoparathyroidism (PHP) type Ia is characterized by hypocalcemia due to PTH resistance and by features of Albright's hereditary osteodystrophy, including short stature, obesity, subcutaneous calcification and brachydactyly. A wide variety of clinical and biochemical manifestations have been reported. We report two cases of PHP type Ia in duozygotic twins with different phenotypes. The proband was a 10-yr-old girl. She showed subcutaneous ossification, shortening of the metacarpal bone, short stature, obesity and round face. She had normocalcemia (8.9 mg/dl), high-normal phosphate (5.0 mg/dl) and increased levels of serum intact PTH (152 pg/ml) and TSH (9.17 μIU/ml) levels. Her twin younger brother had atypical Albright's hereditary osteodystrophy with only mild obesity and subcutaneous calcifications, but he showed a low level of serum calcium (7.0 mg/dl) and high levels of serum phosphate (7.6 mg/dl), intact PTH (377 pg/ml) and TSH (6.9 μIU/ml). We diagnosed them as having PHP type Ia on the basis of clinical and biochemical findings, Ellsworth-Howard test and family history. There is considerable variability in clinical and biochemical features of PHP type Ia even among affected duozygotic twins. The differences of intrauterine environment and growth history cannot account for the variable phenotypes of PHP type Ia. Even if a patient shows no AHO features, examination of all family members should be undertaken. PMID:24790309

  19. Genetics 101 --The Hereditary Material of Life

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Genetics 101 Genetics 101 — The Hereditary Material of Life Past Issues / Summer 2013 Table of Contents Genetics is the study of heredity, the process in ...

  20. Genetics Home Reference: hereditary cerebral amyloid angiopathy

    Science.gov (United States)

    ... prognosis of a genetic condition? Genetic and Rare Diseases Information Center Frequency The prevalence of hereditary cerebral amyloid angiopathy is unknown. The Dutch type is the most common, with over 200 ...

  1. Hereditary non-BRCA gynecological tumors.

    Science.gov (United States)

    Vellone, Valerio G; Paudice, Michele; Varesco, Liliana

    2016-10-01

    Early diagnosis and proper management of gynecologic malignancies represent a challenge in modern oncology. A growing interest has arisen around the gynecological manifestations of hereditary cancer syndromes. In particular, the discovery of the BRCA1 and BRCA2 genes in ovarian cancer and the mismatch repair genes (MMR) in endometrial carcinoma has revolutionized our approach to the diagnosis and screening of women for ovarian and uterine cancers. The clinical, genetic and pathological features of hereditary cancer syndromes with gynecological manifestations are reviewed focusing on Lynch Syndrome, also known as hereditary nonpolyposis colorectal carcinoma (HNPCC), Peutz-Jeghers Syndrome (PJS), Cowden Syndrome or multiple hamartoma syndrome, Gorlin Syndrome or nevoid basal-cell carcinoma syndrome (NBCCS) and Reed's Syndrome or hereditary leiomyomatosis and renal cell cancer (HLRCC). PMID:26930387

  2. A Review of Hereditary Fructose Intolerance

    Directory of Open Access Journals (Sweden)

    Mogoş Tiberius

    2016-03-01

    Full Text Available Fructose intolerance is a metabolic disorder with hereditary determinism, clinically manifested on terms of fructose intake. Untreated, hereditary fructose intolerance may result in renal and hepatic failure. Unfortunately, there are no formal diagnostic and surveillance guidelines for this disease. If identified and treated before the occurrence of permanent organ damage, patients can improve their symptoms and self-rated health. Implementation and adherence to a strict fructose free diet is often difficult, but not impossible.

  3. Hereditary Transthyretin Amyloidosis in Eight Chinese Families

    OpenAIRE

    Ling-Chao Meng; He Lyu; Wei Zhang; Jing Liu; Zhao-Xia Wang; Yun Yuan

    2015-01-01

    Background: Mutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis. ...

  4. Case of hereditary papillary renal cell carcinoma

    OpenAIRE

    Mustafa, Sadaf; Jadidi, Nima; Faraj, Sheila F.; Rodriquez, Ronald

    2012-01-01

    Renal cell carcinoma is the most common type of renal malignancy and it originates from the renal tubular epithelium. Due to the diversity in the histopathological and molecular characteristics, it is typically subclassified into five different categories. Papillary renal cell carcinoma is one subclassification and it includes two variants: sporadic and hereditary. Although the hereditary form comprises a smaller number of cases of papillary renal cell carcinoma, an understanding of the molec...

  5. Hereditary leiomyomatosis and renal cell carcinoma

    OpenAIRE

    Schmidt LS; Linehan WM

    2014-01-01

    Laura S Schmidt,1,2 W Marston Linehan11Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; 2Basic Science Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USAAbstract: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal-dominant hereditary syndrome, which is caused by germline mutations in the FH gene that encodes the tricarboxylic ac...

  6. Hereditary Predispositions to Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Sarah A. Bannon

    2016-05-01

    Full Text Available Myelodysplastic syndromes (MDS are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA, dyskeratosis congenita (DC, Diamond–Blackfan anemia (DBA, and Shwachman–Diamond syndrome (SBS, hallmarked by clinically-recognizable phenotypes (e.g., radial ray anomalies in FA and significantly increased risks for MDS and/or acute myeloid leukemia (AML in the setting of bone marrow failure. However, additional families with multiple cases of MDS or AML have long been reported in the medical literature with little known regarding potential hereditary etiologies. Over the last decade, genomic investigation of such families has revealed multiple genes conferring inherited risks for MDS and/or AML as the primary malignancy, including RUNX1, ANKRD26, DDX41, ETV6, GATA2, and SRP72. As these syndromes are increasingly appreciated in even apparently de novo presentations of MDS, it is important for hematologists/oncologists to become familiar with these newly-described syndromes. Herein, we provide a review of familial MDS syndromes and practical aspects of management in patients with predisposition syndromes.

  7. Hereditary haemoglobin disorders in Brazil.

    Science.gov (United States)

    Zago, M A; Costa, F F

    1985-01-01

    The data on the incidence and variability of hereditary haemoglobin (Hb) disorders in Brazil are reviewed. The most common abnormalities are HbS, HbC and beta-thalassaemias. Both homozygotes and compound heterozygotes for these genes (i.e., HbS/HbC disease, S/beta-thalassaemia, C/beta-thalassaemia) are common, owing to the free miscegenation of populations of Mediterranean and African ancestry. The diversity of beta-thalassaemias is similar to that observed in other regions. beta(0)-Thalassaemia is more frequent than the beta(+) variant among affected individuals. Most patients are descendants of Italian immigrants but occasional cases have other racial origins. Patients with thalassaemia major are mostly beta (0) homozygotes, while thalassaemia intermedia is more heterogeneous, including a variety of genotypes. alpha-Thalassaemias are not common although cases of HbH disease have been reported. Isolated examples of several Hb variants have been described, and two abnormal Hb were first found in Brazil: Hb Porto Alegre and Hb Niteroi. PMID:3898485

  8. Ecallantide: in acute hereditary angioedema.

    Science.gov (United States)

    Garnock-Jones, Karly P

    2010-07-30

    Ecallantide, a recombinant protein that is a selective, highly potent and reversible inhibitor of human plasma kallikrein, is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in patients aged >or=16 years. In the randomized, double-blind, placebo-controlled, multicentre, phase III trial EDEMA3, mean symptom response to treatment at 4 hours (assessed using the Treatment Outcome Score [TOS]; primary endpoint) was significantly greater with a single subcutaneous dose of ecallantide 30 mg than with placebo in patients with acute, moderate to severe attacks of HAE. In addition, the mean change from baseline in symptom severity at 4 hours (assessed using the Mean Symptom Complex Severity [MSCS] scale) was significantly greater with ecallantide than with placebo. At 4 hours in the similarly designed EDEMA4 trial, the mean change from baseline in MSCS score (primary endpoint) and mean TOS were both significantly greater in recipients of a single subcutaneous dose of ecallantide 30 mg than in placebo recipients. Subcutaneous ecallantide 30 mg was generally well tolerated in patients with acute attacks of HAE in the EDEMA3 and EDEMA4 trials. Adverse events were mostly of mild to moderate severity, and no event that was more common in ecallantide than placebo recipients occurred in >10% of patients. PMID:20614949

  9. Cadmium toxicity to ringed seals (Phoca hispida): an epidemiological study of possible cadmium-induced nephropathy and osteodystrophy in ringed seals (Phoca hispida) from Qaanaaq in Northwest Greenland

    DEFF Research Database (Denmark)

    Sonne-Hansen, C; Dietz, R; Leifsson, P S;

    2002-01-01

    the skeleton nor to the cadmium concentrations. Furthermore, the degree of mineralisation of the skeleton was not correlated with the cadmium concentration, age or sex. It can therefore be concluded that despite high levels of cadmium, none of the ringed seals showed any signs of cadmium......-induced nephropathy or osteodystrophy. This might be explained by the composition of the ringed seals diet, which contains high levels of vitamin D, calcium, phosphorus, zinc, selenium and protein. These elements are all likely to counteract cadmium-induced damage. It is speculated that ringed seal are not...

  10. DESIGNING AND OPPORTUNITY FUEL WITH BIOMASS AND TIRE-DERIVED FUEL FOR COFIRING AT WILLOW ISLAND GENERATING STATION AND COFIRING SAWDUST WITH COAL AT ALBRIGHT GENERATING STATION

    Energy Technology Data Exchange (ETDEWEB)

    K. Payette; D. Tillman

    2004-06-01

    During the period July 1, 2000-March 31, 2004, Allegheny Energy Supply Co., LLC (Allegheny) conducted an extensive demonstration of woody biomass cofiring at its Willow Island and Albright Generating Stations. This demonstration, cofunded by USDOE and Allegheny, and supported by the Biomass Interest Group (BIG) of EPRI, evaluated the impacts of sawdust cofiring in both cyclone boilers and tangentially-fired pulverized coal boilers. The cofiring in the cyclone boiler--Willow Island Generating Station Unit No.2--evaluated the impacts of sawdust alone, and sawdust blended with tire-derived fuel. The biomass was blended with the coal on its way to the combustion system. The cofiring in the pulverized coal boiler--Albright Generating Station--evaluated the impact of cofiring on emissions of oxides of nitrogen (NO{sub x}) when the sawdust was injected separately into the furnace. The demonstration of woody biomass cofiring involved design, construction, and testing at each site. The results addressed impacts associated with operational issues--capacity, efficiency, and operability--as well as formation and control of airborne emissions such as NO{sub x}, sulfur dioxide (SO{sub 2}2), opacity, and mercury. The results of this extensive program are detailed in this report.

  11. Genetics Home Reference: hereditary myopathy with early respiratory failure

    Science.gov (United States)

    ... list from the University of Kansas Medical Center: Muscular Dystrophy / Atrophy GeneReviews (1 link) Hereditary Myopathy with Early Respiratory Failure (HMERF) Genetic Testing Registry (1 link) Hereditary myopathy with early ...

  12. Genetics Home Reference: distal hereditary motor neuropathy, type V

    Science.gov (United States)

    ... neuropathy, type V distal hereditary motor neuropathy, type V Enable Javascript to view the expand/collapse boxes. ... Close All Description Distal hereditary motor neuropathy, type V is a progressive disorder that affects nerve cells ...

  13. Hereditary Cerebellar Ataxias: A Korean Perspective

    Directory of Open Access Journals (Sweden)

    Ji Sun Kim

    2015-05-01

    Full Text Available Hereditary ataxia is a heterogeneous disorder characterized by progressive ataxia combined with/without peripheral neuropathy, extrapyramidal symptoms, pyramidal symptoms, seizure, and multiple systematic involvements. More than 35 autosomal dominant cerebellar ataxias have been designated as spinocerebellar ataxia, and there are 55 recessive ataxias that have not been named systematically. Conducting genetic sequencing to confirm a diagnosis is difficult due to the large amount of subtypes with phenotypic overlap. The prevalence of hereditary ataxia can vary among countries, and estimations of prevalence and subtype frequencies are necessary for planning a diagnostic strategy in a specific population. This review covers the various hereditary ataxias reported in the Korean population with a focus on the prevalence and subtype frequencies as the clinical characteristics of the various subtypes.

  14. Disease expression in women with hereditary angioedema

    DEFF Research Database (Denmark)

    Bouillet, Laurence; Longhurst, Hilary; Boccon-Gibod, Isabelle;

    2008-01-01

    OBJECTIVE: Fluctuations in sex hormones can trigger angioedema attacks in women with hereditary angioedema. Combined oral contraceptive therapies, as well as pregnancy, can induce severe attacks. The course of angioedema may be very variable in different women. STUDY DESIGN: Within the PREHAEAT...... project launched by the European Union, data on 150 postpubertal women with hereditary angioedema were collected in 8 countries, using a patient-based questionnaire. RESULTS: Puberty worsened the disease for 62%. Combined oral contraceptives worsened the disease for 79%, whereas progestogen-only pills...

  15. Extramedullary paraspinal hematopoiesis in hereditary spherocytosis

    Directory of Open Access Journals (Sweden)

    Gogia P

    2008-01-01

    Full Text Available Hereditary spherocytosis (HS is a common inherited hemolytic anemia due to red cell membrane defects. Extramedullary hematopoiesis is a compensatory response to insufficient bone marrow blood cell production. The preferred sites of extramedullary hematopoietic involvement are the spleen, liver and lymph nodes; but in HS, the posterior paravertebral mediastinum is also commonly involved. We report a case of a 50-year-old male who presented to us in respiratory distress and with bilateral paravertebral posterior mediastinal masses, which on trucut biopsy were found to be extra-hematopoietic masses; and the patient was found to have hereditary spherocytosis.

  16. Ovarian Cancer in Hereditary Cancer Susceptibility Syndromes.

    Science.gov (United States)

    Nakonechny, Quentin B; Gilks, C Blake

    2016-06-01

    Hereditary breast and ovarian cancer (HBOC) syndrome and Lynch syndrome (LS) are associated with increased risk of developing ovarian carcinoma. Patients with HBOC have a lifetime risk of up to 50% of developing high-grade serous carcinoma of tube or ovary; patients with LS have a 10% lifetime risk of developing endometrioid or clear cell carcinoma of the ovary. Testing all patients with tubo-ovarian high-grade serous carcinoma for mutations associated with HBOC syndrome, and all patients presenting with endometrioid or clear cell carcinoma of the ovary for mutations associated with LS can identify patients with undiagnosed underlying hereditary cancer susceptibility syndromes. PMID:27241103

  17. HEREDITARY SPASTIC PARAPLEGIA: FROM GENE TO CLINIC

    Directory of Open Access Journals (Sweden)

    Seyyed Hasan TONEKABONI

    2010-04-01

    Full Text Available ObjectiveHereditary Spastic Paraplegia (HSP is a degenerative disease of genetic origin affecting the corticospinal tracts in the spinal cord. There are three forms of inheritance: Autosomal dominant HSP, Autosomal rececive HSP and X-linked HSP.This disease is characterized by progressive spasticity of leg muscles with varying degrees of stiffness and weakness of other muscle groups. In this review, we will discuss the latest findings on  the pathophysiology of axonal degeneration and all the responsible genetic defects in HSP.Keyword: Hereditary spastic paraplegia, degenerative disease, inheritance

  18. Genetic profiles distinguish different types of hereditary ovarian cancer

    DEFF Research Database (Denmark)

    Domanska, Katarina; Malander, Susanne; Staaf, Johan;

    2010-01-01

    Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian canc...

  19. Hereditary Acrodermatitis Enteropathica In Two Siblings

    Directory of Open Access Journals (Sweden)

    Masood Quzi

    2003-01-01

    Full Text Available Acrodermatitis enteropathica is a rare hereditary disorder of zinc metabolism characterized by dermatitis involving the acral and periorificial skin, diarrhea and growth retardation. Two siblings with classical features of acrodermatitis enteropathic and an autosomal recessive pattern of inheritance are described here.

  20. Uncommon Cone-Beam Computerized Tomography Findings in McCune-Albright Syndrome in an Implant Candidate Patient: A Case Report

    Directory of Open Access Journals (Sweden)

    Khoshhal

    2013-06-01

    Full Text Available Introduction McCune-Albright syndrome is a rare disease, characterized by triad of cafe-au-lait spots, endocrinopathies and fibrous dysplasia. These bone lesions are usually revealed during the first decade of life, together with pain, pathological fractures and secondary deformities. Case Presentation A 40-year-old female patient presented an opaque lesion at the left mandibular side of face, in a cone-beam computerized tomography (CBCT view, during the implant placement evaluations. The patient had experienced precocious puberty and had undergone hysterectomy. Unilateral cafe-au-lait spots were present on patient’s left side of the face. There was no expansion in intraoral examination. The oral mucosa was also normal. No asymmetry was detected. The analysis of sample histopathology confirmed fibrous dysplasia. Discussion In this patient we preferred following up. Afterwards, total surgical lesion resection can be performed. After a long-term follow-up, the area may receive an implant.

  1. Epidemiology of Non-hereditary Angioedema

    DEFF Research Database (Denmark)

    Madsen, Flemming; Attermann, Jorn; Linneberg, Allan

    2012-01-01

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n = 7,931) and in a sample of Danish patients (n = 7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...... abdominal area, 17% had diarrhoea, 11% had vomiting and 6% fainted during attacks. Non-hereditary angioedema has high lifetime prevalence and becomes chronic in approximately 50% of affected patients. Symptoms in the larynx and throat, as well as non-specific symptoms, such as dizziness and abdominal pain......) reported a lifetime prevalence of 7.4% for angioedema. In both groups symptoms were most frequent in the lips, head, neck, eyes and tongue. In the C1 INH test normal group angioedema was still active at the time of the study in 53% of the patients, and 36% reported symptoms in the throat, 23% in the...

  2. Hereditary spastic paraplegia with cerebellar ataxia

    DEFF Research Database (Denmark)

    Nielsen, J E; Johnsen, B; Koefoed, P;

    2004-01-01

    identified in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the...... significantly relatively decreased regional cerebral blood flow in most of the cerebellum. We conclude that this kindred demonstrates a considerable overlap between cerebellar ataxia and spastic paraplegia, emphasizing the marked clinical heterogeneity of HSP associated with spastin mutations.......Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria...

  3. Coexistence of hereditary angioedema and Turner's syndrome.

    OpenAIRE

    Fletcher, A; Weetman, A P

    1998-01-01

    A 34-year-old woman presented to the out-patient clinic with angioedema and type II hereditary angioedema was confirmed immunologically. She also volunteered she had never had a menstrual period and physical examination identified several features of Turner's syndrome. A mosaic karyotype with XY and XO was found on chromosomal analysis and gonadectomy was performed in view of the high risk of gonadoblastoma. After commencing oestrogen at physiological replacement doses, the patient experience...

  4. Hereditary mucoepithelial dysplasia and severe respiratory distress

    OpenAIRE

    Mahmoud Halawa; Abu-Hasan, Mutasim N; ElMallah, Mai K.

    2015-01-01

    Hereditary mucoepithelial dysplasia (HMD) is a rare autosomal dominant disorder characterized by mucoepithelial disruption of the skin, hair and mucous membranes. It results from defective gap junction formation and leads to non-scarring alopecia, mucosal erythema, perineal erythematous intertrigo, involvement of the conjunctival mucosa, and pulmonary disease. We present a case of severe respiratory distress in an initially healthy full term infant born to a mother with HMD. This infant later...

  5. REHABILITATION OF CHILDREN WITH HEREDITARY MYOPATHY

    OpenAIRE

    Vera Anatolevna Erokhina

    2015-01-01

    Now the problem of rehabilitation of children with various hereditary diseases gains special relevance because the number of children with genetic abnormalities is growing. These genetic abnormalities cause changes in the development and functioning of their psyche, for example, create special features of their cognitive processes.The purpose of this study is to examine the impact of the psycho-correctional work on the state of psycho-cognitive functions of children with congenital myopathy. ...

  6. Hereditary Transthyretin Amyloidosis in Eight Chinese Families

    Institute of Scientific and Technical Information of China (English)

    Ling-Chao Meng; He Lyu; Wei Zhang; Jing Liu; Zhao-Xia Wang; Yun Yuan

    2015-01-01

    Background:Mutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis,which occurs worldwide.To date,more and more mutations in the TTR gene have been reported.Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family.The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis.Methods:Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014.Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients,for light and electron microscopy examination.The TTR genes from the nine patients were analyzed.Results:The onset age varied from 23 to 68 years.The main manifestations were paresthesia,proximal and/or distal weakness,autonomic dysfunction,cardiomyopathy,vitreous opacity,hearing loss,and glossohypertrophia.Nerve biopsy demonstrated severe loss ofmyelinated fibers in seven cases and amyloid deposits in three.One patient had skin amyloid deposits which were revealed from electron microscopic examination.Genetic analysis showed six kinds of mutations of TTR gene,including Val30Met,Phe33Leu,Ala36Pro,Val30Ala,Phe33Val,and Glu42Gly in exon 2.Conclusions:Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients,the screening for TTR mutations should be performed in all the adult patients,who are clinically suspected with hereditary TTR amyloidosis.

  7. Hereditary Transthyretin Amyloidosis in Eight Chinese Families

    Directory of Open Access Journals (Sweden)

    Ling-Chao Meng

    2015-01-01

    Full Text Available Background: Mutations of transthyretin (TTR cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis. Methods: Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed. Results: The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2. Conclusions: Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.

  8. Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis

    OpenAIRE

    Santos, Paulo C.J.L.; Krieger, Jose E.; Pereira, Alexandre C.

    2012-01-01

    Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by enhanced intestinal absorption of dietary iron. Without therapeutic intervention, iron overload leads to multiple organ damage such as liver cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin pigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for p.Cys282Tyr or p.Cys282Tyr/p.His63Asp compound heterozygosity. In addition to HFE gene, mutations in the genes that encode hem...

  9. The Diagnosis and Management of Hereditary Haemochromatosis

    OpenAIRE

    Clark, Paul; Britton, Laurence J; Powell, Lawrie W

    2010-01-01

    Hereditary haemochromatosis (HH) is a common genetic disorder of iron metabolism in individuals of Northern European ancestry which leads to inappropriate iron absorption from the intestine and iron overload in susceptible individuals. Iron overload is suggested by elevations in serum ferritin and transferrin saturation. The majority of patients with clinically significant iron overload are homozygous for the C282Y mutation of the HFE gene, however only a minority of C282Y homozygotes fully e...

  10. Hereditary fructose intolerance in Brazilian patients

    OpenAIRE

    Eugênia Ribeiro Valadares; Ana Facury da Cruz; Talita Emile Ribeiro Adelino; Viviane de Cássia Kanufre; Maria do Carmo Ribeiro; Maria Goretti Moreira Guimarães Penido; Luciano Amedee Peret Filho; Valadares, Laís Maria Santos Valadares e

    2015-01-01

    Introduction: Hereditary fructose intolerance (HFI) is a rare inborn error of carbohydrate metabolism, autosomal recessive, caused by mutations in the gene ALDOB, leading to deficiency of aldolase B. Symptoms begin in the first months of life with the introduction of complementary foods containing fructose, sucrose or sorbitol, often with vomiting, feeding problems and failure to thrive. Prolonged exposure may cause liver and kidney failure, which can lead to death. Treatment consists in remo...

  11. Osteodistrofia fibrosa em equinos criados em pastagem de Panicum maximum cultivar Aruana: relato de casos Fibrous osteodystrophy in horses raised on Aruana (Panicum maximum pasture: case reports

    Directory of Open Access Journals (Sweden)

    B.R. Curcio

    2010-02-01

    Full Text Available Relata-se a ocorrência de osteodistrofia fibrosa em 38 equinos criados em pastagens de Panicum maximum cultivar Aruana, da raça Mangalarga Marchador, provenientes de uma propriedade localizada no estado do Paraná. No exame clínico geral, observou-se aumento bilateral e simétrico dos ossos da face e, também, aumento de volume na porção distal do rádio. A análise radiológica das áreas afetadas demonstrou redução da densidade óssea, e, na bioquímica sanguínea, 24 (63% animais apresentaram níveis de fósforo elevados. O exame bromatológico revelou níveis elevados de oxalato na pastagem de Aruana. Conclui-se que a ingestão de Aruana, forragem com altos níveis de oxalato, foi responsável pelo aparecimento de lesões de osteodistrofia fibrosa em equinos.Fibrous osteodystrophy occurrence is reported in 38 Mangalarga Marchador horses raised on Aruana (Panicum maximum pasture from a breeding farm in Paraná state. Clinical examination showed bilateral and symmetric increase in bones of face and an increase of volume at the radius distal portion. The radiologic analysis revealed bone density reduction in affected areas. Blood biochemist demonstrated high phosphorus levels in 24 animals (63%. Analysis of the pasture was performed and high levels of oxalate were found in the Aruana samples. It was concluded that the ingestion of Aruana, a pasture with high oxalate levels, was responsible for the appearing of fibrous osteodystrophy lesions in horses.

  12. Medical management of hereditary optic neuropathies

    Directory of Open Access Journals (Sweden)

    ChiaraLa Morgia

    2014-07-01

    Full Text Available Hereditary optic neuropathies are diseases of the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e. the maternally inherited Leber’s Hereditary Optic Neuropathy (LHON and Dominant Optic Atrophy (DOA. They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1 and 14484/ND6 for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone. Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising venue that still needs to be validated.

  13. Cytotoxic and targeted therapy for hereditary cancers.

    Science.gov (United States)

    Iyevleva, Aglaya G; Imyanitov, Evgeny N

    2016-01-01

    There is a number of drugs demonstrating specific activity towards hereditary cancers. For example, tumors in BRCA1/2 mutation carriers usually arise via somatic inactivation of the remaining BRCA allele, which makes them particularly sensitive to platinum-based drugs, PARP inhibitors (PARPi), mitomycin C, liposomal doxorubicin, etc. There are several molecular assays for BRCA-ness, which permit to reveal BRCA-like phenocopies among sporadic tumors and thus extend clinical indications for the use of BRCA-specific therapies. Retrospective data on high-dose chemotherapy deserve consideration given some unexpected instances of cure from metastatic disease among BRCA1/2-mutated patients. Hereditary non-polyposis colorectal cancer (HNPCC) is characterized by high-level microsatellite instability (MSI-H), increased antigenicity and elevated expression of immunosuppressive molecules. Recent clinical trial demonstrated tumor responses in HNPCC patients treated by the immune checkpoint inhibitor pembrolizumab. There are successful clinical trials on the use of novel targeted agents for the treatment or rare cancer syndromes, e.g. RET inhibitors for hereditary medullary thyroid cancer, mTOR inhibitors for tumors arising in patients with tuberous sclerosis (TSC), and SMO inhibitors for basal-cell nevus syndrome. Germ-line mutation tests will be increasingly used in the future for the choice of the optimal therapy, therefore turnaround time for these laboratory procedures needs to be significantly reduced to ensure proper treatment planning. PMID:27555886

  14. Pamidronic acid and cabergoline as effective long-term therapy in a 12-year-old girl with extended facial polyostotic fibrous dysplasia, prolactinoma and acromegaly in McCune-Albright syndrome: a case report

    OpenAIRE

    Classen Carl; Mix Monika; Kyank Ulrike; Hauenstein Christina; Haffner Dieter

    2012-01-01

    Abstract Introduction McCune-Albright syndrome is a complex inborn disorder due to early embryonal postzygotic somatic activating mutations in the GNAS1 gene. The phenotype is very heterogeneous and includes polyostotic fibrous dysplasia, typically involving the facial skull, numerous café-au-lait spots and autonomous hyperfunctions of several endocrine systems, leading to hyperthyroidism, hypercortisolism, precocious puberty and acromegaly. Case presentation Here, we describe a 12-year-old C...

  15. Hereditary pancreatitis and mutation of the trypsinogen gene

    OpenAIRE

    Weber, P; Keim, V; Zimmer, K.

    1999-01-01

    Hereditary pancreatitis is a rare form of chronic recurrent pancreatitis. A family, in which 11 members had chronic pancreatitis, five had diabetes, and two had pancreatic cancer, was studied, and hereditary pancreatitis was diagnosed in all patients by demonstrating the mutation in exon 3 of the cationic trypsinogen gene (R117H). The clinical implications of genotypic analysis in hereditary pancreatitis are discussed.



  16. Hereditary Colorectal Cancer (CRC Program in Latvia

    Directory of Open Access Journals (Sweden)

    Irmejs Arvids

    2003-12-01

    Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

  17. Diagnosis and Management of Hereditary Carcinoids.

    Science.gov (United States)

    Benafif, Sarah; Eeles, Rosalind

    2016-01-01

    Carcinoid tumours arise in cells of the diffuse neuroendocrine system and can develop in a number of anatomical sites including the lungs and the gastrointestinal tract. There has been a move away from the use of the term carcinoid tumour to the more appropriate use of neuroendocrine tumour (NET) to highlight the potential for invasion and metastasis associated with some NETs. Although most cases are sporadic, 15-20% of cases are related to a hereditary syndrome, the most common of these being multiple endocrine neoplasia 1 (MEN1). Other hereditary syndromes include the following: von Hippel-Lindau (VHL), neurofibromatosis 1 and tuberous sclerosis complex (TSC), which are all associated with a germline mutation of the associated tumour suppressor gene and an autosomal dominant inheritance pattern. Familial small intestinal NET (SI NET) is a recently described condition which is also inherited in an autosomal dominant manner. There appears to be more than one causative gene; thus far, only the IPMK gene has been identified as a causative germline mutation. This was identified by carrying out whole-exome sequencing of germline and tumour DNA in a family with multiple members diagnosed with SI NET. Identification of NET predisposition genes in other families via these methods will allow the development of dedicated NET gene panels which can be used to screen NET patients and at-risk relatives for hereditary mutations. Close surveillance of at-risk individuals is important to detect NETs early when curative surgery can be offered and the morbidity and mortality of metastatic NETs can be avoided. PMID:27075353

  18. Hypogonadotropic Hypogonadism Associated with Hereditary Hemorrhagic Telengiectasia

    Directory of Open Access Journals (Sweden)

    Scarano Valentina

    2013-01-01

    Full Text Available A 65-year-old man was referred to our clinic for the rehabilitation of right hemiparesis caused by ischaemic stroke. Hypertension, postphlebitic syndrome of lower limbs, frequent nose bleeding, and anemia were present in his history; in his adolescence, he was treated for idiopathic hypogonadotropic hypogonadism. Further investigations have revealed also microsomia, suggesting a clinical diagnosis of Kallmann syndrome, that is, an association, possible in males and females, of hypogonadotropic hypogonadism with olfactory deficits. A definite diagnosis of hereditary hemorrhagic telangiectasia was made based on clinical criteria and confirmed by genetic analysis.

  19. Molecular basis of hereditary C3 deficiency.

    OpenAIRE

    Botto, M.; Fong, K. Y.; So, A K; Rudge, A; Walport, M.J. (Mark J.)

    1990-01-01

    Hereditary deficiency of complement component C3 in a 10-yr-old boy was studied. C3 could not be detected by RIA of serum from the patient. Segregation of C3 S and C3 F allotypes within the family confirmed the presence of a null gene for C3, for which the patient was homozygous. 30 exons have been characterized, spanning the entire beta chain of C3 and the alpha chain as far as the C3d region. Sequence analysis of the exons derived from the C3 null gene showed no abnormalities in the coding ...

  20. Management of hereditary angioedema: 2010 Canadian approach

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    Bowen Tom

    2010-07-01

    Full Text Available Abstract C1-inhibitor (C1-INH deficiency is a rare blood disorder resulting in angioedema attacks that are debilitating and may be life-threatening. Prophylaxis and therapy of events has changed since our first Canadian Consensus Conference on the diagnosis, therapy and management of HAE. We have formed the Canadian Hereditary Angioedema Network (CHAEN/Réseau Canadien d'Angioédème Héréditaire (RCAH - http://www.haecanada.com to advance care of patients with this disorder in Canada. We here present a review of management of HAE in Canada.

  1. Hereditary mucoepithelial dysplasia and severe respiratory distress

    Directory of Open Access Journals (Sweden)

    Mahmoud Halawa

    2015-01-01

    Full Text Available Hereditary mucoepithelial dysplasia (HMD is a rare autosomal dominant disorder characterized by mucoepithelial disruption of the skin, hair and mucous membranes. It results from defective gap junction formation and leads to non-scarring alopecia, mucosal erythema, perineal erythematous intertrigo, involvement of the conjunctival mucosa, and pulmonary disease. We present a case of severe respiratory distress in an initially healthy full term infant born to a mother with HMD. This infant later developed signs and symptoms of HMD. A high index of suspicion for pulmonary infection with atypical organism is essential in infants with a family history of HMD who present with respiratory distress.

  2. Skin deposits in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Gudmundsson, G

    1990-01-01

    Clinically normal skin from 47 individuals aged 9-70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic....... Skin from 12 individuals who served as controls and skin from 14 close relatives of the patients was negative for amyloid. Punch biopsy of the skin is a simple procedure which is of value for the diagnosis of HCCA, even before the appearance of clinical symptoms. This method might also be of use in...

  3. Hereditary subshifts whose simplex of invariant measures is Poulsen

    OpenAIRE

    Kułaga-Przymus, Joanna; Lemańczyk, Mariusz; Weiss, Benjamin

    2015-01-01

    We give a sufficient condition for the simplex of invariant measures for a hereditary system to be Poulsen. In particular, we show that this simplex is Poulsen in case of positive entropy $\\mathscr{B}$-free systems. We also give an example of a positive entropy hereditary system whose simplex of invariant measures is not Poulsen.

  4. Cerebral abscesses among Danish patients with hereditary haemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Tørring, P M; Nissen, H;

    2013-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs), which due to paradoxical embolization may cause cerebral abscess.......Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs), which due to paradoxical embolization may cause cerebral abscess....

  5. The first familial case of inherited 2q37.3 interstitial deletion with isolated skeletal abnormalities including brachydactyly type E and short stature.

    Science.gov (United States)

    Jean-Marçais, Nolwenn; Decamp, Matthieu; Gérard, Marion; Ribault, Virginie; Andrieux, Joris; Kottler, Marie-Laure; Plessis, Ghislaine

    2015-01-01

    Albright hereditary osteodystrophy (AHO)-like syndrome is also known as brachydactyly-mental retardation syndrome (BDMR; OMIM 60040). This disorder includes intellectual disability in all patients, skeletal abnormalities, including brachydactyly E (BDE) in approximately half, obesity, and facial dysmorphism. Patients with 2q37 microdeletion or HDAC4 mutation are defined as having an AHO-like phenotype with normal stimulatory G (Gs) function. HDAC4 is involved in neurological, cardiac, and skeletal function. This paper reports the first familial case of 2q37.3 interstitial deletion affecting two genes, HDAC4 and TWIST2. Patients presented with BDE and short stature without intellectual disability, showing that haploinsufficiency of the HDAC4 critical region may lead to a spectrum of phenotypes, ranging from isolated brachydactyly type E to BDMR. PMID:25402011

  6. Identification of a Novel Mutation in a Pseudohypoparathyroidism Family

    Directory of Open Access Journals (Sweden)

    Zhi-Min Miao

    2011-01-01

    Full Text Available Pseudohypoparathyroidism type Ia (PHP Ia is defined as a series of disorders characterized by multihormone resistance in end-organs and Albright hereditary osteodystrophy (AHO phenotype. PHP Ia is caused by heterozygous inactivating mutations in GNAS, which encodes the stimulatory G-protein alpha subunit (Gsa. A patient with typical clinical manifestations of pseudohypoparathyroidism (PHP (round face, short stature, centripetal obesity, brachydactyly, and multi-hormone resistance: parathyroid hormone (PTH, thyroid-stimulating hormone (TSH, and gonadotropins presented at our center. The sequence of the GNAS gene from the patient and her families revealed a novel missense mutation (Y318H in the proband and her mother. An in vitro Gsa functional study showed that Gsa function was significantly impaired. These results stress the importance of GNAS gene investigation.

  7. Pseudohypoparathyroidism (a report of 6 patients in a family)

    International Nuclear Information System (INIS)

    Objective: To improve the recognition and diagnosis of pseudohypoparathyroidism (PhP). Methods: Six subjects with PhP of 4 generations in one family were investigated and studied. There were 4 males (including 2 deaths) and 2 females. The age of 4 surviving patients was from 8 to 55 years. All cases were proved by clinical biochemistry tests. Plain film of hands and head CT scans were performed in 2 selected patients. Results: The somatotype of Albright hereditary osteodystrophy (AHO) and short fingers and toes were found in all cases. Radiologic features were as follows: (1) short metacarpals and phalanges. (2) skull thickening and symmetrical calcification of basal ganglia. Conclusion: The diagnosis of PHP can be established by close combination of radiologic findings and clinical manifestations

  8. BRCA1/2 associated hereditary breast cancer

    Institute of Scientific and Technical Information of China (English)

    Li-song TENG; Yi ZHENG; Hao-hao WANG

    2008-01-01

    Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCA1 and/or BRCA2 genes. In this review, we provide an overview of these two genes,focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial;further studies are needed to elucidate the nature of BRCA1/2 associated hereditary breast cancers.

  9. Genetic profiles distinguish different types of hereditary ovarian cancer

    DEFF Research Database (Denmark)

    Domanska, Katarina; Malander, Susanne; Staaf, Johan; Karlsson, Anna; Borg, Ake; Jönsson, Göran; Nilbert, Mef

    2010-01-01

    Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer...... (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers as a...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....

  10. Analysis on the relationship between renal osteodystrophy and the biochemical marker of bone turnover and other related factors in patients with chronic kidney diseases

    International Nuclear Information System (INIS)

    Objective: To investigate the relationship between renal osteodystrophy and the biochemical marker of bone turnover in patients with chronic kidney diseases. Methods: A total of 102 patients with chronic kidney diseases (CKD) and 52 healthy subjects (normal control) were included in this study. The level of total procollagen type Ⅰ amino-terminal propeptide of (TP Ⅰ NP), β-isomerized carboxyterminal propeptide (β-CTx), intact parathyroid hormone (iPTH), serum calcium (Ca2+), serum phosphorus (P), alkaline phosphatase (ALP) were detected. The correlations between renal osteodystrophy in the patients with chronic kidney diseases and other related factors were analyzed. Results: Compared with the normal control group, there were higher TP Ⅰ NP, β-CTx, iPTH, P, ALP, Cr, Bun and β2-MG, in the CKD group which were significantly different according to Mann-Whitney U test (P<0.05 or <0.01). The Ca2+ and 1, 25-OH Vitamin d3 [1, 25 (OH)2D3] in the CKD group were significantly decreased compared with the normal control group (P<0.05). Correlation analysis showed TP Ⅰ NP was positively correlated with β-CTx, iPTH, P, CaxP, ALP, Cr, Bun, β2-MG (r was 0.790, 0.681, 0.573, 0.541, 0.550, 0.598, 0.793 respectively, P<0.01), Correlation analysis showed β-CTx was positively correlated with iPTH, P, CaxP, ALP, Cr, Bun, β2-MG (r was 0.803, 0.527, 0.449, 0.659, 0.672, 0.565, 0.624 respectively, P<0.01). TP Ⅰ NP was negatively correlated with Ca2+ and 1, 25 (OH)2D3 (r was -0.302, -0.582 respectively, P<0.01). β-CTx was negatively correlated with Ca2+ and 1, 25 (OH)2D3 (r was -0.265, -0.595 respectively, P<0.01). The iPTH was positively correlated with age, TP Ⅰ NP, β-CTx, P, CaxP, ALP, Cr, Bun and β2-MG (r was 0.485, 0.681, 0.803, 0.630, 0.541, 0.486, 0.690, 0.648, 0.531 respectively, P<0.05 or <0.01), but was negatively correlated with Ca2+ and 1, 25 (OH)2D3 (r was -0.318, -0.621 respectively, P<0.05). Conclusion: The application of total procollagen type

  11. REHABILITATION OF CHILDREN WITH HEREDITARY MYOPATHY

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    Vera Anatolevna Erokhina

    2015-12-01

    Full Text Available Now the problem of rehabilitation of children with various hereditary diseases gains special relevance because the number of children with genetic abnormalities is growing. These genetic abnormalities cause changes in the development and functioning of their psyche, for example, create special features of their cognitive processes.The purpose of this study is to examine the impact of the psycho-correctional work on the state of psycho-cognitive functions of children with congenital myopathy. A complete cycle of psycho-pedagogical correction was conducted among 27 patients with hereditary myopathies (18 boys and 9 girls. A comprehensive neuropsychological study, which assessed the status and dynamics of the cognitive functions of patients was conducted before and after the rehabilitation. The main effect of the fulfilled directed rehabilitation program was the improvement of visual-spatial perception and energy functional structures implementing neurodynamic component activities.The results can be applied by psycho-pedagogical specialists and specialists of clinical profile in assisting patients with disorders of the musculoskeletal system.

  12. Epidemiology of Non-hereditary Angioedema

    DEFF Research Database (Denmark)

    Madsen, Flemming; Attermann, Jørn; Linneberg, Allan

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n¿=¿7,931) and in a sample of Danish patients (n¿=¿7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...... abdominal area, 17% had diarrhoea, 11% had vomiting and 6% fainted during attacks. Non-hereditary angioedema has high lifetime prevalence and becomes chronic in approximately 50% of affected patients. Symptoms in the larynx and throat, as well as non-specific symptoms, such as dizziness and abdominal pain......) reported a lifetime prevalence of 7.4% for angioedema. In both groups symptoms were most frequent in the lips, head, neck, eyes and tongue. In the C1 INH test normal group angioedema was still active at the time of the study in 53% of the patients, and 36% reported symptoms in the throat, 23% in the...

  13. Pavlodar city children's some hereditary diseases

    International Nuclear Information System (INIS)

    Territory of the Pavlodar region directly adjoining to the Semipalatinsk test site is unique object for study of many year tests consequences on population health. Health worsening caused by small doses of radiation on artificial pollution background is defined. Purpose of the work is Pavlodar city children's some hereditary diseases (Downs syndrome, crack of upper lip and/or palate, hemophilia) under study of frequency dynamic of statistical data within period from 1980 by 1995. It is defined: a) tendency to growth Downs syndrome frequency has been distinctly observed beginning of the 1982; b) it is noted Downs syndrome frequency growth stabilization within period from 1988 by 1991; c) among children with Downs syndrome is distinguished low viability; d) there is rather higher correlation rate of Downs syndrome and congenial heart threshold against average statistical index; e) character of frequencies changes of crack of upper lip and/or palate has tendency to growth; f) it is defined that boys predominate among children with this disease; g) congenial crack of soft palate have being revealed as solitary thresholds of development; h) genealogy analysis of hemophilia sick reveals, that it has only hereditary character. 8 refs

  14. Case report of GNAS epigenetic defect revealed by a congenital hypothyroidism.

    Science.gov (United States)

    Romanet, Pauline; Osei, Lindsay; Netchine, Irène; Pertuit, Morgane; Enjalbert, Alain; Reynaud, Rachel; Barlier, Anne

    2015-04-01

    Pseudohypoparathyroidism (PHP) is a group of disorders characterized by end-organ resistance to the parathyroid hormone (PTH). PHP type 1A includes multihormone resistance syndrome, Albright's hereditary osteodystrophy, and obesity and is caused by mutations in GNAS exon 1 through 13. PHP type 1B (PHP1B), caused by epigenetic changes in the GNAS locus, was initially described as an isolated resistance to PTH. Epigenetic changes in GNAS have also been reported in patients who display mild Albright's hereditary osteodystrophy or mild thyroid-stimulating hormone (TSH) resistance without mutation of GNAS. Here we report a case of PHP caused by epigenetic changes in GNAS in a patient with congenital hypothyroidism. The patient was referred for a positive newborn screening for hypothyroidism (TSH 50 mIU/L). She exhibited severe clinical features of congenital hypothyroidism. The thyroid was in place, and etiologic explorations were negative. TSH was normalized under L-thyroxin, and the symptoms disappeared, except for a macroglossia. In childhood, PHP was suspected in addition to elevated PTH, obesity, brachydactyly, and a rounded face. Sequencing, methylation analysis, and large deletion research were performed in GNAS. No genetic mutations were found. Methylation analysis revealed a broad epigenetic defect without deletion in GNAS consistent with sporadic PHP1B. The multilocus methylation analysis were negative. This finding expands the known onsets of PHP1B and emphasizes the need for a new PHP classification system. This case report has important consequences for the etiologic diagnosis of congenital hypothyroidism because it adds a new cause of the disease. PMID:25802348

  15. Brazilian guidelines for the diagnosis and treatment of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Pedro Giavina-Bianchi

    2011-01-01

    Full Text Available Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with multiple organ involvement. It is caused by a quantitative or functional deficiency of the C1 inhibitor, which is a member of the serine protease inhibitor family. Hereditary angioedema is unknown to many health professionals and is therefore an underdiagnosed disease. The causes of death from hereditary angioedema include laryngeal edema with asphyxia. The estimated mortality rate in patients in whom the disease goes undetected and who are therefore incorrectly treated is 25-40%. In addition to edema of the glottis, hereditary angioedema often results in edema of the gastrointestinal tract, which can be incapacitating. Patients with hereditary angioedema may undergo unnecessary surgical interventions because the digestive tract can be the primary or only organ system involved, thus mimicking acute surgical abdomen. It is estimated that patients with hereditary angioedema experience some degree of disability 20-100 days per year. The Experts in Clinical Immunology and Allergy of the "Associação Brasileira de Alergia e Imunopatologia -ASBAI" developed these guidelines for the diagnosis, therapy, and management of hereditary angioedema.

  16. {sup 99m}Tc(V)-DMSA scintigraphy in monitoring the response of bone disease to vitamin D{sub 3} therapy in renal osteodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Sarikaya, A.; Sen, S.; Hacimahmutoglu, S.; Pekindil, G. [Trakya Univ., Edirne (Turkey). Faculty of Medicine

    2002-02-01

    Renal osteodystrophy (ROD) is a common and serious complication for uremic patients and patients are treated with 1,25-dihydroxyvitamin D{sub 3}. The bone scanning agent {sup 99m}Tc-phosphate has also been used to evaluate in ROD but it is not clear that bone scintigraphy has a role in the follow-up of treatment. In this study {sup 99m}Tc(V)-DMSA scintigraphy was performed in eleven patients [age 40.7{+-}17.3 (mean {+-}SD) yr] with ROD before and after vitamin D{sub 3} therapy. Images were obtained after hemodialysis performed following tracer injection to maintain normal blood levels of the radiopharmaceutical and to reduce soft tissue activity. Lumbar vertebra-to-soft tissue uptake ratios (LUR) were quantified with the planar {sup 99m}Tc(V)-DMSA images. Alkaline phosphatase and parathyroid hormone levels after tretment had significantly decreased compared with pre-therapy. In all patients there was visually decreased uptake in bone structures after treatment. After treatment the mean LUR ratio was significantly lower than those of before treatment (3.59{+-}2.63 vs. 1.65{+-}0.62; p=0.01). LUR values were correlated with pre-therapy alkaline phosphatase and parathyroid hormone. These findings indicate that {sup 99m}Tc(V)-DMSA scintigraphy is sensitive in evaluating the response of ROD to vitamin D{sub 3} therapy. (author)

  17. 99mTc(V)-DMSA scintigraphy in monitoring the response of bone disease to vitamin D3 therapy in renal osteodystrophy

    International Nuclear Information System (INIS)

    Renal osteodystrophy (ROD) is a common and serious complication for uremic patients and patients are treated with 1,25-dihydroxyvitamin D3. The bone scanning agent 99mTc-phosphate has also been used to evaluate in ROD but it is not clear that bone scintigraphy has a role in the follow-up of treatment. In this study 99mTc(V)-DMSA scintigraphy was performed in eleven patients [age 40.7±17.3 (mean ±SD) yr] with ROD before and after vitamin D3 therapy. Images were obtained after hemodialysis performed following tracer injection to maintain normal blood levels of the radiopharmaceutical and to reduce soft tissue activity. Lumbar vertebra-to-soft tissue uptake ratios (LUR) were quantified with the planar 99mTc(V)-DMSA images. Alkaline phosphatase and parathyroid hormone levels after treatment had significantly decreased compared with pre-therapy. In all patients there was visually decreased uptake in bone structures after treatment. After treatment the mean LUR ratio was significantly lower than those of before treatment (3.59±2.63 vs. 1.65±0.62; p=0.01). LUR values were correlated with pre-therapy alkaline phosphatase and parathyroid hormone. These findings indicate that 99mTc(V)-DMSA scintigraphy is sensitive in evaluating the response of ROD to vitamin D3 therapy. (author)

  18. Pulmonary hypertension in hereditary haemorrhagic telangiectasia

    Institute of Scientific and Technical Information of China (English)

    Veronique; MM; Vorselaars; Sebastiaan; Velthuis; Repke; J; Snijder; Jan; Albert; Vos; Johannes; J; Mager; Martijn; C; Post

    2015-01-01

    Hereditary haemorrhagic telangiectasia(HHT) is an autosomal dominant inherited disorder characterised by vascular malformations in predominantly the brain,liverand lungs.Pulmonary hypertension(PH) is increasingly recognised as a severe complication of HHT.PH may be categorised into two distinct types in patients with HHT.Post-capillary PH most often results from a high pulmonary blood flow that accompanies the high cardiac output state associated with liver arteriovenous malformations.Less frequently,the HHT-related gene mutations in ENG or ACVRL1 appear to predispose patients with HHT to develop pre-capillary pulmonary arterial hypertension.Differentiation between both forms of PH by right heart catheterisation is essential,since both entities are associated with severe morbidity and mortality with different treatment options.Therefore all HHT patients should be referred to an HHT centre.

  19. Dementia in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Blöndal, H; Guomundsson, G; Benedikz, Eirikur;

    1989-01-01

    Nineteen cases with verified Hereditary Cystatin C Amyloid Angiopathy are presented. All of the cases had one or more cerebrovascular insults starting at the age of 20-41 years and survived from 10 days to 23 years after the first insult. Progressive dementia was a prominent clinical feature in...... seventeen cases of whom two presented with dementia. At the last examination the majority had severe dementia and severely abnormal EEG. Anti-cystatin C positive amyloid vascular and perivascular infiltrates were found. The resulting damage to the microvasculature of the brain and secondary hemorrhages and...... infarctions were considered to be an adequate explanation for the dementia in these cases. Skin biopsies can now probably be used to demonstrate cystatin C positive amyloid deposits conclusively in the tissues of these patients....

  20. Hereditary History Preserving Bisimilarity Is Undecidable

    DEFF Research Database (Denmark)

    Jurdzinski, Marcin; Nielsen, Mogens

    History preserving bisimilarity (hp-bisimilarity) and hereditary history preserving bisimilarity (hhp-bisimilarity) are behavioural equivalences taking into account causal relationships between events of concurrent systems. Their prominent feature is being preserved under action refinement, an...... operation important for the top-down design of concurrent systems. We show that-unlike hp-bisimilarity-checking hhp-bisimilarity for finite labelled asynchronous transition systems is not decidable, by a reduction from the halting problem of 2-counter machines. To make the proof more transparent we...... introduce an intermediate problem of checking domino bisimilarity for origin constrained tiling systems, whose undecidability is interesting in its own right. We also argue that the undecidability of hhp-bisimilarity holds for finite labelled 1-safe Petri nets....

  1. Idebenone for Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Gueven, N

    2016-03-01

    Idebenone is a rapidly absorbed, safe and well-tolerated drug and is currently the only clinically proven treatment option for Leber's hereditary optic neuropathy (LHON) patients. Idebenone (Raxone®) is approved by the European Medicines Agency for the treatment of LHON and has been available on the European market since 2015. Due to its molecular mode of action of bypassing the defective mitochondrial complex I, idebenone leads to improved energy supply and a functional recovery of retinal ganglion cells during the acute stage of the disease, thereby preventing further vision loss and promoting recovery of vision. Thus, commencing treatment shortly after the onset of symptoms is likely to have the best therapeutic effect, a hypothesis that is supported by the available clinical data. PMID:27186591

  2. Hereditary renal adysplasia: new observations and hypotheses.

    Science.gov (United States)

    Moerman, P; Fryns, J P; Sastrowijoto, S H; Vandenberghe, K; Lauweryns, J M

    1994-01-01

    Renal agenesis and dysplasia are frequently regarded by pathologists, even pediatric pathologists, as sporadic malformations. We report six fetal autopsy cases of hereditary renal adysplasia (HRA): two pairs of siblings, one case with paternal unilateral renal agenesis, and one case with an autosomal balanced 6p/19q translocation. The main purpose of this paper is to emphasize that nonsyndromal renal agenesis and dysplasia are pathogenetically related and often inherited as an autosomal dominant trait with incomplete penetrance and variable expression. A subsidiary purpose is to present a case of bilateral multicystic dysplasia with a balanced 6p/19q translocation. This observation further supports the assignment of one of the loci for HRA to chromosome 6p. PMID:8065999

  3. [Therapeutic possibilities of hereditary diseases in dermatology].

    Science.gov (United States)

    Schnyder, U W

    1983-01-01

    Several years ago the therapeutic possibilities for the treatment of inherited skin disorders were rather restricted; recently new possibilities have been developed and successfully applied. The author discusses the indications for a surgical procedure in basal cell nevus syndrome and the satisfying results revealed by dermabrasion in sebaceous adenoma of Pringle. The use of a low phenylalanine and tyrosine diet in case of palmoplantar keratosis with tyrosinemia is of theoretical as well as practical interest. However, a most striking therapeutic success is obtained by the treatment with drugs. The substitution of zinc in acrodermatitis enteropathica is very effective and not expensive! The positive effect of phenytoin in epidermolysis bullosa cicatricans is based on the partial inhibition of collagenase activity by this drug. Finally the author discusses the advantages of a treatment with retinoids in different hereditary keratinization disorders. PMID:6666938

  4. Icatibant in hereditary angioedema: news and challenges.

    Science.gov (United States)

    Bouillet, Laurence

    2011-05-01

    Hereditary angioedema (HAE) is a rare condition. Its prognosis depends on whether there is laryngeal involvement with a risk of asphyxia, which is present in 25% of such cases. Improved understanding of the pathophysiology of this disease has resulted in the development of targeted therapies including icatibant, which acts as an antagonist at bradykinin B2 receptors. This agent has been shown to be effective in the treatment of attacks of HAE in three Phase III randomized double-blind published studies. Efficacy data have been collected in all types of attack: cutaneous, abdominal and laryngeal. Safety data are also encouraging. Icatibant is administered subcutaneously, with the potential for patients to self-administer. In the future, this therapy may offer increased independence for HAE patients. PMID:21595592

  5. Hereditary Angioedema - Consequences of a New Treatment Paradigm in Denmark

    DEFF Research Database (Denmark)

    Bygum, Anette

    2014-01-01

    Experiences from a Danish patient cohort with hereditary angioedema are reported with focus on home therapy and burden of illness. Eighty patients have been prospectively followed over 11 years, having experienced a total of 7,809 attacks over 469 patient years. More than half of the patients...... stopped long-term prophylaxis with danazol or tranexamic acid and changed treatment regimen to on-demand treatment with C1 inhibitor concentrate or icatibant. At least 10% of the attacks remained un-treated. More than half of the patients felt that hereditary angioedema had a significant psychological...... therapy has profoundly improved the lives of hereditary angioedema patients....

  6. An MRI study of hereditary spinocerebellar degenerations

    Energy Technology Data Exchange (ETDEWEB)

    Konagaya, Masaaki; Konagaya, Yoko; Morishita, Shinji; Nakamuro, Takuya (Nara Medical Univ., Kashihara (Japan))

    1990-06-01

    Magnetic resonance (MR) images were reviewed in 21 patients with hereditary spinocerebellar degeneration (SCD) of autosomal dominant trait to assess the potential of MR imaging for classifying clinical types. On the basis of size of the cerebellar vermis and ventral pons, the patients were classified as having atrophy in the vermis and pons (Group I, n=12), vermian atrophy and less significant atrophy in the pons (Group II, n=6), and no significant atrophy in either the vermis or pons (Group III, n=3). Twelve patients in Group I were subdivided into Group Ia (5 patients) having the normal midbrain tegmentum and Group Ib (7 patients) having reduced midbrain tegmentum. Patients in Group Ia seemed to have Menzel type olivo-ponto-cerebellar atrophy (OPCA). Those in Group Ib had frequently ataxia, spasticity, ocular symptoms, bladder dysfunction, and amyotrophy with or without fasciculation, suggesting a special type of SCD mimicking Joseph disease, Menzel type OPCA, and dentate-rubro-pallido-luysian atrophy. Six patients in Group II were clinically diagnosed as having Holmes type late cerebral cortex atrophy (LCCA). MR imaging revealed medial dominant cerebellar atrophy. In 3 patients in Group III with a history of long illness, MR imaging showed slight changes in the cerebellum, mildly atrophic inferior cerebellar peduncle, and normal midbrain tegmentum and red nucleus. They were considered to have Joseph disease or hereditary spastic ataxia. MR imaging was capable of classifying typical Menzel type OPCA or Holmes type LCCA. In the presence of various symptoms, however, MRI failed to differentiate them. For diseases mimicking Joseph disease, atrophy seemed to be less in the cerebellum and pons than that for Menzel type OPCA. MRI failed to reveal specific changes in predominantly truncal ataxia and spasticity. (N.K.).

  7. Hereditary colon Cancer: Recommendations for prevention

    International Nuclear Information System (INIS)

    Prevention in individuals with hereditary risk of colon cancer, is subject to clinical and molecular facts because their behavior differs to sporadic cancer. Hereditary cancer diseases affecting the colon in particular linked to other locations or that are associated with pre-cancer (polyps, osteoma s, lentigines) phenotypic markers represent a dissimilar to those who present directly in colorectal cancer status or associated conditions. In the first, the presence of previous injury (phenotypes) allows us to identify, while the latter is essential to have other diagnostic pathway (genotypes) .The location of genomic alterations manages to delve into the problem and identify those who will develop disease. The perspective will be different in the general population and those who do not carry mutations in terms suggestions for prevention, both primary and secondary. Not always the mutation is detected and in these high-risk situations, the clinic is sovereign and agrees to keep all members of these events surveillance strict about not being able to characterize those who are carriers of alterations and our condition is different in the proposition of preventive attitudes: set from when control about which organs and often starts, suffer because of accelerated carcinogenesis. The presentation is focused on populations at increased risk of cancer colorectal, regarding the management of the suggestions for primary prevention, secondary prevention while analyzing the early diagnosis of the disease and the suggestion of treatment, compared to the general population management. Primary prevention, including chemo prevention are described. While in secondary prevention is emphasized to management time tracking, optimization diagnostics according to the pathology suspected, the most common therapeutic approaches and findings relating prophylactic surgery

  8. Squamous cell carcinoma complicating an hereditary epidermo-lysis bullosa

    International Nuclear Information System (INIS)

    The dystrophic form of hereditary epidermo-lysis bullosa is associated with an increased frequency of squamous cell carcinoma. We report a new case. An 18-year-old patient, carrying a Hallopeau Siemens hereditary epidermo-lysis bullosa, presented a subcutaneous nodular lesion, for 1 year that ulcerated and budded with inguinal lymphadenopathy. The histological study ted to the conclusion of a well differentiated squamous cell carcinoma. The patient was treated surgically. Tumor and metastatic lymph nodes were excised. A radiotherapy was decided but the postoperative course was fatal due to an infection and to a deterioration of her general condition. Squamous cell carcinoma frequently occurs on the cicatricial lesion of hereditary epidermo-lysis bullosa and usually affects males with recessive hereditary epidermo-lysis bullosa. Metastases are frequent, precocious and multiple. The treatment may be surgical. The particularities of our observation are the young age of patient and the localization. (author)

  9. Genetics Home Reference: hereditary leiomyomatosis and renal cell cancer

    Science.gov (United States)

    ... Central Sudarshan S, Pinto PA, Neckers L, Linehan WM. Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer-- ... with a qualified healthcare professional . About Genetics Home Reference Site Map Contact Us Selection Criteria for Links ...

  10. Mechanisms of postural instability in hereditary spastic paraplegia

    NARCIS (Netherlands)

    Nonnekes, J.; Niet, M. de; Nijhuis, L.B.; Bot, S.T. de; Warrenburg, B.P.C. van de; Bloem, B.R.; Geurts, A.C.H.; Weerdesteyn, V.G.M.

    2013-01-01

    Hereditary spastic paraplegia (HSP) is characterized by progressive lower extremity spasticity and weakness, due to retrograde axonal degeneration of the corticospinal tract and posterior spinal columns. HSP patients fall frequently. We hypothesized that delayed postural responses contribute to thei

  11. Genetics Home Reference: infantile-onset ascending hereditary spastic paralysis

    Science.gov (United States)

    ... and paraplegia result from degeneration (atrophy) of motor neurons , which are specialized nerve cells in the brain and spinal cord that control muscle movement. Hereditary spastic paraplegias are divided into two types: pure and complicated. The pure types involve only ...

  12. Hereditary breast cancer. Psychosocial issues and family physicians' role.

    OpenAIRE

    Carroll, J. C.; Heisey, R. E.; Warner, E.; V Goel; McCready, D R

    1999-01-01

    OBJECTIVES: To outline the psychosocial issues in hereditary breast cancer (HBC) assessment and discuss the role of family physicians. QUALITY OF EVIDENCE: A literature search using MEDLINE, CINAHL, CancerLit, and HealthStar databases was conducted from January 1990 to April 1998, using the key words breast cancer or neoplasm and familial or hereditary, genetic testing or screening, primary care or family physician or counseling, genetic counseling, psychosocial or psychological. We found onl...

  13. Pyoderma Gangrenosum in a Patient With Hereditary Spherocytosis.

    Science.gov (United States)

    Kwon, Hyoung Il; Paek, Jun Oh; Kim, Jeoung Eun; Ro, Young Suck; Ko, Joo Yeon

    2016-03-01

    Pyoderma gangrenosum (PG) is a rare, relapsing cutaneous disease with 4 distinctive clinical manifestations: ulcerative, bullous, pustular, and vegetative lesions. It mainly occurs in adults and is frequently associated with systemic diseases, most commonly inflammatory bowel disease, rheumatologic disease, or hematological dyscrasias. However, there have been no previous reports of PG in a patient with hereditary spherocytosis, a common inherited hemolytic anemia. We report here a unique case of PG in a 15-year-old boy with underlying hereditary spherocytosis. PMID:26711368

  14. Low Vision Rehabilitation in Patients with Hereditary Retinal Dystrophy

    OpenAIRE

    İkbal Seza Petriçli; Aysun İdil Merdoğan; Zuhal Özen Tunay; Özdemir Özdemir

    2015-01-01

    Objectives: To examine the methods of low vision rehabilitation in patients with hereditary retinal dystrophy. Materials and Methods: This study was conducted in Ankara University Faculty of Medicine, Ophthalmology Department of Low Vision Rehabilitation and Research Unit between January 2005 and May 2013. The diagnosis of 181 of 1841 patients referred to this unit was determined as hereditary retinal dystrophy (HRD). Patients were grouped according to their distant and near visual a...

  15. Matroids, hereditary collections and simplicial complexes having boolean representations

    OpenAIRE

    Rhodes, John; Silva, Pedro V.

    2012-01-01

    Inspired by the work of Izakhian and Rhodes, a theory of representation of hereditary collections by boolean matrices is developed. This corresponds to representation by finite $\\vee$-generated lattices. The lattice of flats, defined for hereditary collections, lattices and matrices, plays a central role in the theory. The representations constitute a lattice and the minimal and strictly join irreducible elements are studied, as well as various closure operators.

  16. Hereditary angioedema: quality of life in Brazilian patients

    OpenAIRE

    Gomide, Maria Abadia Consuelo M S; Eliana Toledo; Solange Oliveira Rodrigues Valle; Campos, Regis A.; Alfeu T. França; Nieves Prior Gomez; Heitor Franco Andrade Jr.; Teresa Caballero; Grumach, Anete S.

    2013-01-01

    OBJECTIVE: Hereditary angioedema is a serious medical condition caused by a rare autosomal dominant genetic disorder and it is associated with deficient production or dysfunction of the C1 esterase inhibitor. In most cases, affected patients experience unexpected and recurrent crises of subcutaneous, gastrointestinal and laryngeal edema. The unpredictability, intensity and other factors associated with the disease impact the quality of life of hereditary angioedema patients. We evaluated the ...

  17. Systemic treatment for hereditary cancers: a 2012 update

    OpenAIRE

    Imyanitov, Evgeny N.; Byrski, Tomasz

    2013-01-01

    The history of specific therapy for hereditary tumors dates back to mid 1980s and involves a number of reports demonstrating regression of familial colon polyps upon administration of sulindac. Virtually no clinical studies on other hereditary cancer types were available until the year 2009, when Byrski et al. presented the data on unprecedented sensitivity of BRCA1-associated breast malignancies to cisplatin. This breakthrough has revived interest to the treatment of cancer in germ-line muta...

  18. Genetic basis of hereditary colorectal cancers: Hereditary nonpolyposis colorectal cancer and Familial adenomatous polyposis

    OpenAIRE

    Renkonen, Elise

    2006-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) are characterized by a high risk and early onset of colorectal cancer (CRC). HNPCC is due to a germline mutation in one of the following MMR genes: MLH1, MSH2, MSH6 and PMS2. A majority of FAP and attenuated FAP (AFAP) cases are due to germline mutations of APC, causing the development of multiple colorectal polyps. To date, over 450 MMR gene mutations and over 800 APC mutations have been identified. Mo...

  19. Pamidronic acid and cabergoline as effective long-term therapy in a 12-year-old girl with extended facial polyostotic fibrous dysplasia, prolactinoma and acromegaly in McCune-Albright syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Classen Carl

    2012-01-01

    Full Text Available Abstract Introduction McCune-Albright syndrome is a complex inborn disorder due to early embryonal postzygotic somatic activating mutations in the GNAS1 gene. The phenotype is very heterogeneous and includes polyostotic fibrous dysplasia, typically involving the facial skull, numerous café-au-lait spots and autonomous hyperfunctions of several endocrine systems, leading to hyperthyroidism, hypercortisolism, precocious puberty and acromegaly. Case presentation Here, we describe a 12-year-old Caucasian girl with severe facial involvement of fibrous dysplasia, along with massive acromegaly due to growth hormone excess and precocious puberty, with a prolactinoma. Our patient was treated with a bisphosphonate and the prolactin antagonist, cabergoline, resulting in the inhibition of fibrous dysplasia and involution of both the prolactinoma and growth hormone excess. During a follow-up of more than two years, no severe side effects were noted. Conclusion Treatment with bisphosphonates in combination with cabergoline is a suitable option in patients with McCune-Albright syndrome, especially in order to circumvent surgical interventions in patients suffering from polyostotic fibrous dysplasia involving the skull base.

  20. Hypercoagulability in hereditary hemorrhagic telangiectasia with epilepsy

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2015-01-01

    Full Text Available Recent data indicate that in patients with hereditary hemorrhagic teleangiectasia (HHT, low iron levels due to inadequate replacement after hemorrhagic iron losses are associated with elevated factor-VIII plasma levels and consecutively increased risk of venous thrombo-embolism. Here, we report a patient with HHT, low iron levels, elevated factor-VIII, and recurrent venous thrombo-embolism. A 64-year-old multimorbid Serbian gipsy was diagnosed with HHT at age 62 years. He had a history of recurrent epistaxis, teleangiectasias on the lips, renal and pulmonary arterio-venous malformations, and a family history positive for HHT. He had experienced recurrent venous thrombosis (mesenteric vein thrombosis, portal venous thrombosis, deep venous thrombosis, insufficiently treated with phenprocoumon during 16 months and gastro-intestinal bleeding. Blood tests revealed sideropenia and elevated plasma levels of coagulation factor-VIII. His history was positive for diabetes, arterial hypertension, hyperlipidemia, smoking, cerebral abscess, recurrent ischemic stroke, recurrent ileus, peripheral arterial occluding disease, polyneuropathy, mild renal insufficiency, and epilepsy. Following recent findings, hypercoagulability was attributed to the sideropenia-induced elevation of coagulation factor-VIII. In conclusion, HHT may be associated with hypercoagulability due to elevated factor-VIII associated with low serum iron levels from recurrent bleeding. Iron substitution may prevent HHT patients from hypercoagulability.

  1. Hereditary angioedema: classification, pathogenesis, and diagnosis.

    Science.gov (United States)

    Banerji, Aleena

    2011-01-01

    Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder associated with a deficiency in C1 inhibitor. More than 200 mutations in this gene, located on chromosome 11, have been identified. Although HAE is often inherited, 20-25% of cases are from new spontaneous mutations and they have no family history of swelling. Decreased C1 inhibitor activity leads to inappropriate activation of multiple pathways, including the complement and contact systems and the fibrinolysis and coagulation systems. Reduced C1 inhibitor activity results in increased activation of plasma kallikrein-kinin system proteases and increased bradykinin levels. Bradykinin is felt to be the main mediator of symptoms in HAE. Patients with HAE have recurrent episodes of swelling of the extremities, abdomen, face, and upper airway. Angioedema involving the gastrointestinal tract can lead to intestinal wall edema, which results in abdominal pain, nausea, vomiting, and diarrhea. Laryngeal swelling is life-threatening and may lead to asphyxia. Common triggers of an attack include trauma, stress, infection, menstruation, oral contraceptives, hormone replacement therapy, and angiotensin-converting enzyme inhibitors. Laboratory testing including C4, C1 inhibitor level, and function is needed to confirm or rule out the diagnosis of HAE. The treatment of HAE has improved significantly in recent years with the availability of several safe and effective therapies. Several consensus guidelines have been created to further assist in the management of HAE patients. This review will provide an update on the classification, pathophysiology, clinical presentation, and diagnosis of HAE. PMID:22221432

  2. Multimodal Imaging in Hereditary Retinal Diseases

    Directory of Open Access Journals (Sweden)

    Francesco Pichi

    2013-01-01

    Full Text Available Introduction. In this retrospective study we evaluated the multimodal visualization of retinal genetic diseases to better understand their natural course. Material and Methods. We reviewed the charts of 70 consecutive patients with different genetic retinal pathologies who had previously undergone multimodal imaging analyses. Genomic DNA was extracted from peripheral blood and genotyped at the known locus for the different diseases. Results. The medical records of 3 families of a 4-generation pedigree affected by North Carolina macular dystrophy were reviewed. A total of 8 patients with Stargardt disease were evaluated for their two main defining clinical characteristics, yellow subretinal flecks and central atrophy. Nine male patients with a previous diagnosis of choroideremia and eleven female carriers were evaluated. Fourteen patients with Best vitelliform macular dystrophy and 6 family members with autosomal recessive bestrophinopathy were included. Seven patients with enhanced s-cone syndrome were ascertained. Lastly, we included 3 unrelated patients with fundus albipunctatus. Conclusions. In hereditary retinal diseases, clinical examination is often not sufficient for evaluating the patient’s condition. Retinal imaging then becomes important in making the diagnosis, in monitoring the progression of disease, and as a surrogate outcome measure of the efficacy of an intervention.

  3. Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis

    Directory of Open Access Journals (Sweden)

    Paulo C. J. L. Santos

    2012-02-01

    Full Text Available Hereditary hemochromatosis (HH is an autosomal recessive disorder characterized by enhanced intestinal absorption of dietary iron. Without therapeutic intervention, iron overload leads to multiple organ damage such as liver cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin pigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for p.Cys282Tyr or p.Cys282Tyr/p.His63Asp compound heterozygosity. In addition to HFE gene, mutations in the genes that encode hemojuvelin (HJV, hepcidin (HAMP, transferrin receptor 2 (TFR2 and ferroportin (SLC40A1 have been associated with regulation of iron homeostasis and development of HH. The aim of this review was to identify the main gene mutations involved in the pathogenesis of type 1, 2, 3 and 4 HH and their genetic testing indication. HFE testing for the two main mutations (p.Cys282Tyr and p.His63Asp should be performed in all patients with primary iron overload and unexplained increased transferrin saturation and/or serum ferritin values. The evaluation of the HJV p.Gly320Val mutation must be the molecular test of choice in suspected patients with juvenile hemochromatosis with less than 30 years and cardiac or endocrine manifestations. In conclusion, HH is an example that genetic testing can, in addition to performing the differential diagnostic with secondary iron overload, lead to more adequate and faster treatment.

  4. Eosinophils in hereditary and inflammatory myopathies.

    Science.gov (United States)

    Schröder, Thomas; Fuchss, Johann; Schneider, Ilka; Stoltenburg-Didinger, Gisela; Hanisch, Frank

    2013-12-01

    It is not known whether eosinophilic myositis is a specific histopathological feature of limb girdle muscular dystrophy 2A (LGMD2A). Number and location of eosinophils in skeletal muscle biopsies (n=100) was analysed by Giemsa and modified hematoxylin/eosin staining in patients with genetically confirmed myopathies (LGMD2A, LGMD2B, LGMD2L, facioscapulohumeral muscular dystrophy, dystrophinopathy), histologically confirmed idiopathic inflammatory myopathies (sporadic inclusion body myositis (sIBM), dermatomyositis (DM), polymyositis), amyotrophic lateral sclerosis (neurogenic control), and normal controls. The number of eosinophils/mm² was significantly higher in LGMD2A, PM, DM, and sIBM compared to controls but not significantly higher than other myopathies. A large overlap in the number of eosinophils/mm2 between all groups was seen. In all disease groups eosinophils were mainly found endomysially (46- 88%) and intra- and perivascularly (4-37%). There was no correlation between the numbers of eosinophils/mm² and (i) age at biopsy and (ii) the duration of the disease. The extent of myopathic, fibrotic, and inflammatory changes did not differ in samples with high and low eosinophil count. Eosinophils seem to represent an unspecific histological finding in hereditary and inflammatory myopathies, but also amyotrophic lateral sclerosis. PMID:24803842

  5. Hereditary Angioedema Presenting as Recurrent Acute Pancreatitis.

    Science.gov (United States)

    Berger, Tal D; Garty, Ben-Zion

    2016-02-01

    Hereditary angioedema (HAE) may manifest with swelling of the face, extremities, and upper airways. Gastrointestinal symptoms are also common and may include abdominal pain, vomiting, and diarrhea. However, pancreatic involvement is rare and has been reported only in a few adults with previously diagnosed HAE. We describe a 6-year-old boy who presented with recurrent severe abdominal pain accompanied by an elevation in pancreatic enzyme levels, without subcutaneous or cutaneous angioedema. His symptoms had begun 18 months earlier, and he was hospitalized several times before the present admission with a diagnosis of acute pancreatitis. More comprehensive analysis yielded low levels of C2, C4, CH50, and C1 esterase inhibitor, establishing the diagnosis of HAE. One year after diagnosis, swelling of the extremities appeared for the first time. This is the first report of a child in whom pancreatic disease was the presenting symptom of HAE. HAE should be included in the differential diagnosis of recurrent pancreatitis in children. PMID:26812927

  6. Pathogenesis and laboratory diagnosis of hereditary angioedema.

    Science.gov (United States)

    Zuraw, Bruce L; Christiansen, Sandra C

    2009-01-01

    Hereditary angioedema (HAE) was first described in the 19th century. Over the past 50 years, many details of the pathophysiology and molecular biology of HAE have been elucidated. Two types of HAE, type I and type II, result from mutations in the gene for the broad-spectrum protease inhibitor C1 inhibitor (C1INH). Type I HAE is characterized by low antigenic and functional C1INH levels and type II HAE has normal antigenic but low functional C1INH levels. Type III HAE, by contrast, has normal antigenic and functional C1INH levels. In some families, type III HAE has been linked to mutations in Hageman factor. C1INH is the primary inhibitor of the complement proteases C1r and C1s as well as the contact system proteases activated Hageman factor (coagulation factor XIIa and XIIf) and plasma kallikrein. It is also an inhibitor of plasmin and coagulation factor XIa. The primary mediator of swelling in HAE has now been unequivocally shown to be bradykinin, generated from activation of the plasma contact system. The knowledge gained concerning the underlying mechanisms of the different types of HAE allow the clinician to approach the laboratory diagnosis with confidence and provides opportunities for novel therapeutic strategies. PMID:19843402

  7. Neurological involvement in hereditary hemorrhagic telangiectasia.

    Science.gov (United States)

    Labeyrie, Paul-Emile; Courthéoux, Patrick; Babin, Emmanuel; Bergot, Emmanuel; Touzé, Emmanuel; Pelage, Jean-Pierre

    2016-07-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by epistaxis, telangiectases, and multi-organ vascular dysplasia. Head and neck localizations of HHT are recurrent, frequent associated with serious complications. The aim of this study was to describe the clinical and imaging patterns of neurological involvement in HHT and to discuss the role of interventional radiology in the management of HHT patients. Based on a multidisciplinary experience of twenty years at our center, we report here the different aspects of neurological involvement of HHT. Depending on the genetic type of the disease, vascular abnormalities may affect different organs. The knowledge of neurological involvement according to specific localization of HHT makes detection easier. As cerebral or spinal arteriovenous fistula may be present in patients with epistaxis or pulmonary arteriovenous malformations (PAVMs), radiologists should be able to detect high-risk lesions and prevent related complications. Finally, we review indications and techniques of embolization for hemorrhagic lesions and emphasize that endovascular therapies are very effective and safe in experienced hands. Head and neck imaging is commonly used for the diagnosis of HHT. Imaging plays also a key role for patient evaluation before treatment as pluridisciplinary management is needed. PMID:27059009

  8. 儿童遗传性肾脏疾病%Hereditary kidney diseases in children

    Institute of Scientific and Technical Information of China (English)

    张琰琴; 丁洁; 王芳; 张宏文

    2013-01-01

    About 10 to 15 percent of kidney diseases are inherited or related to genetic factors. While, hereditary kidney diseases have no specific clinical manifestations and react poorly to the therapy, as a result, about 30 percent of hospitalized children with chronic renal failure is due to hereditary kidney diseases in our country. Hereditary kidney diseases are related to many genes. Molecular genetic analysis plays an important role in the diagnosis and prenatal diagnosis of hereditary kidney diseases. Our group have made a series of research in hereditary kidney diseases for nearly 30 years. Here we review the research work and the main results in hereditary kidney diseases of our group.

  9. Hereditary Spherocytosis and Hereditary Elliptocytosis: Aberrant Protein Sorting during Erythroblast Enucleation

    Energy Technology Data Exchange (ETDEWEB)

    Salomao, Marcela; Chen, Ke; Villalobos, Jonathan; Mohandas, Narla; An, Xiuli; Chasis, Joel Anne

    2010-02-08

    During erythroblast enucleation, membrane proteins distribute between extruded nuclei and reticulocytes. In hereditary spherocytosis (HS) and hereditary elliptocytosis (HE), deficiencies of membrane proteins, in addition to those encoded by the mutant gene, occur. Elliptocytes, resulting from protein 4.1R gene mutations, lack not only 4.1R but also glycophorin C, which links the cytoskeleton and bilayer. In HS resulting from ankyrin-1 mutations, band 3, Rh-associated antigen, and glycophorin A are deficient. The current study was undertaken to explore whether aberrant protein sorting, during enucleation, creates these membrane-spanning protein deficiencies. We found that although glycophorin C sorts to reticulocytes normally, it distributes to nuclei in 4.1R-deficient HE cells. Further, glycophorin A and Rh-associated antigen, which normally partition predominantly to reticulocytes, distribute to both nuclei and reticulocytes in an ankyrin-1-deficient murine model of HS. We conclude that aberrant protein sorting is one mechanistic basis for protein deficiencies in HE and HS.

  10. Urinary cyclic adenosine 3',5'-monophosphate response in McCune-Albright syndrome: clinical evidence for altered renal adenylate cyclase activity.

    Science.gov (United States)

    Zung, A; Chalew, S A; Schwindinger, W F; Levine, M A; Phillip, M; Jara, A; Counts, D R; Kowarski, A A

    1995-12-01

    The recent finding of an activating mutation in the Gs alpha protein, the protein that couples receptors to stimulation of adenylate cyclase, from endocrine and nonendocrine tissues of patients with McCune-Albright syndrome (MAS) suggests that alterations in adenylate cyclase activity may account for the clinical abnormalities in these patients. Many patients with MAS have hypophosphatemia. This may result from the presence of the activating Gs alpha mutation in proximal renal tubules or the elaboration of a phosphaturic factor from fibrous dysplasia. We, therefore, sought to characterize renal cAMP generation and phosphate handling in MAS patients. Intravenous infusion of PTH is a classic clinical test used to evaluate hormonal responsiveness of renal proximal tubule adenylate cyclase and examine PTH-dependent phosphate clearance. We performed PTH infusion in 6 MAS patients, 10 normal subjects, and 6 patients with pseudohypoparathyroidism (PHP). The basal urinary cAMP (UcAMP) level in the MAS group [5.5 +/- 2.6 nmol/dL glomerular filtration (GF)] was elevated (P PHP (1.9 +/- 0.6 nmol/dL GF). However, PTH-stimulated peak UcAMP (15.0 +/- 7.0 nmol/dL GF) and the peak/basal UcAMP ratio (3.1 +/- 1.7) in MAS were significantly lower than the respective values in normal subjects (30.8 +/- 16.9 nmol/dL GF and 9.3 +/- 2.9; P PHP (respectively, 3.1 +/- 1.5 nmol/dL GF and 2.0 +/- 1.7). By contrast, the PTH-induced phosphaturic response in MAS patients was similar to that in the normal subjects. Our study provides clinical evidence that MAS patients have altered renal adenylate cyclase activity, manifested by an elevated basal UcAMP, but a blunted UcAMP response to PTH stimulation. These observations are presumably due to a mutation in the Gs alpha protein in the renal tubules. Despite the blunted UcAMP excretion, the phosphaturic response to PTH in MAS patients is intact. PMID:8530601

  11. Hereditary benign telangiectasia: first case in Iran.

    Science.gov (United States)

    Javidi, Zari; Maleki, M; Mashayekhi, V; Nahidi, Y; Omidvar Borna, A

    2006-07-01

    A 14-year-old boy was referred to the Dermatology Clinic of the Medical University of Mashhad, Iran, with numerous cutaneous telangiectasias on the face, ears, lips, and back of the hands, with lesions in the temporal region being the first to appear (Figs 1-3). His mother stated that the lesions had been present for 10 years with an increase in the past 6 months. He had no history of bleeding from the nose, mouth, gastrointestinal tract, and other mucosal surfaces, and there was no sign of organ involvement. On inspection, no lesions were detected on the nasal mucosa, external ear, over the tympanic membrane, or mouth. The patient is one member of a family of six. His mother is healthy, but similar lesions were seen in his father, sister and one of his brothers with similar distributions. Lesions were also seen in his aunt and paternal grandmother, showing disease distribution in six members of this family from three generations. The oldest brother is 20 years of age and mentioned the onset of disease from the age of 10 years. The sister is 18 years of age and lesions started to appear 7 years ago; she claims that the lesions regress during her menstrual period. The youngest brother is 4 years of age and shows no sign of cutaneous lesions as yet. The parents are not consanguineous. Generalized telangiectasia with a predominant distribution on light-exposed skin, an autosomal dominant inheritance, and no sign of systemic or mucosal involvement and bleeding disorders indicates a diagnosis of hereditary benign telangiectasia. Our patient did not consent to biopsy. PMID:16863520

  12. Screening for familial and hereditary prostate cancer.

    Science.gov (United States)

    Lynch, Henry T; Kosoko-Lasaki, Omofolasade; Leslie, Stephen W; Rendell, Marc; Shaw, Trudy; Snyder, Carrie; D'Amico, Anthony V; Buxbaum, Sarah; Isaacs, William B; Loeb, Stacy; Moul, Judd W; Powell, Isaac

    2016-06-01

    Prostate cancer (PC) has the highest degree of genetic transmission of any form of malignancy. In some families, the hereditary pattern is so strong as to mimic an autosomal dominance trait. We reviewed the known predisposing genetic markers to assess possible strategies for screening of families at risk. We carried out a systematic literature search using the Pubmed service of the National Center for Biotechnology Information (NCBI) and several gene libraries, including the NCBI SNP Library, the Online Mendelian Inheritance in Man® Catalog of Human Genes and Genetic Disorders (OMIM) and SNPedia to obtain known gene loci, SNPs and satellite markers associated with PC. We further cross referenced information on identified loci comparing data from different articles and gene reference sites. Whenever possible, we recorded the odds ratio (OR) for the allele associated with PC. In multiple different linkage studies, many independent PC associated loci have been identified on separate chromosomes. Genome-wide association studies have added many more markers to the set derived from linkage investigations. A subset of the alleles is associated with early onset and aggressive cancer. Due to the great heterogeneity, the OR for any one allele predicting future development of this malignancy is low. The strongest predictors are the BRCA2 mutations, and the highly penetrant G84E mutation in HOXB13. The presence of multiple risk alleles is more highly predictive than a single allele. Technical limitations on screening large panels of alleles are being overcome. It is appropriate to begin supplementing prostate specific antigen testing with alleles, such as BRCA2 and HOXB13, disclosed by targeted genomic analysis in families with an unfavorable family cancer history. Future population studies of PC should include genomic sequencing protocols, particularly in families with a history of PC and other malignancies. PMID:26638190

  13. Diagnosis and treatment of hereditary angioedema.

    Science.gov (United States)

    Canonica, G W; Rossi, O

    2012-09-01

    Hereditary angioedema (HAE) is a rare autosomal dominant disorder affecting approximately 1 in 50000 persons. It causes frequent attacks of non-pitting, non-pruritic edema without urticaria, usually of the skin of the extremities, gastrointestinal tract, and upper airways. Gastrointestinal attacks may cause severe pain, and attacks in the laryngeal region may lead to asphyxiation and death. HAE usually begins in childhood or adolescence and persists throughout life. The majority of HAE cases are caused by mutations that result in low levels of functional C1-inhibitor (C1-INH), a serine protease inhibitor that plays regulatory roles in the contact, complement, and fibrinolytic systems. Low C1-INH function results in overproduction of bradykinin, the primary cause of HAE symptoms. Type I HAE is characterized by low levels of functional C1-INH, whereas type II HAE is characterized by normal levels of dysfunctional C1-INH. A third type of HAE has a similar presentation, but is not due to C1-INH deficiency or impairment. Some patients with type III HAE carry mutations in the coagulation factor XII gene that do not alter factor XII plasma levels but markedly increase its activity. HAE is often undiagnosed or misdiagnosed, sometimes leading to inappropriate treatment that may include surgery. HAE should be suspected in any patient who presents with repeated attacks of cutaneous edema without urticaria or recurrent unexplained abdominal pain. Diagnosis requires laboratory testing of complement levels. HAE requires disease-specific treatment with agents that increase functional C1-INH levels and/or reduce the production or activity of bradykinin. These treatments include C1-INH concentrates, icatibant, ecallantide, and attenuated androgens. HAE severely reduces patients' quality of life, which makes supportive care an essential part of the treatment program. PMID:22801442

  14. Outcomes of Lensectomy in Hereditary Lens Subluxation

    Directory of Open Access Journals (Sweden)

    Mohammad-Hossein Dehghan

    2008-12-01

    Full Text Available

    PURPOSE: To evaluate the results of pars plana lensectomy in patients with hereditary lens subluxation. METHOD: Hospital records of patients with hereditary lens subluxation who had undergone pars plana lensectomy at Labbafinejad Medical Center, Tehran-Iran from 1996 to 2003 were reviewed. Patients with more than 6 months of follow up were included. Underlying disorders, best corrected visual acuity (BCVA before and after surgery, intraocular pressure (IOP, postoperative refraction and complications were evaluated. RESULTS: Overall, records of 87 eyes of 49 patients including 27 male and 22 female subjects were reviewed. Mean follow up duration was 20±18 months. Underlying disorders leading to lens subluxation included Marfan syndrome (79.5%, Weill-Marchesani syndrome (8.2%, simple ectopia lentis (8.2%, and homocystinuria (4.1%. The most common indication for surgery was non-correctable refractive error (92.1%. Mean BCVA was 1.13 LogMAR (20/250 preoperatively, which improved to 0.26 LogMAR (20/30-20/40 postoperatively (P < 0.001. BCVA better than 20/40 was achieved in 82.8% of cases after surgery. Angle-supported anterior chamber intraocular lens (ACIOL was implanted in

  15. Anaesthetic management of a patient with hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Nergis Ataol

    2015-12-01

    Full Text Available Hereditary angioedema is a rare autosomal dominant disorder caused by reduced activity of the C1 esterase inhibitor. Patients with hereditary angioedema are clinically characterized by recurrent episodes of swelling of the extremities, face, trunk, airways and abdominal organs. Attacks may occur either spontaneously or following trauma, stress, surgery, infections and hormonal fluctuations. The most common cause of death is asphyxia related to laryngeal edema. Giving C1 esterase inhibitor is the most effective method of treatment. Also fresh frozen plasma, androgen steroids, quinine pathway inhibitors, antifibrinolytics and bradykinin receptor antagonists can be used as treatment. In this paper, the anesthetic management of a patient with hereditary angioedema undergoing inguinal hernia repair surgery is reported.

  16. Autosomal Dominant Hereditary Macrothrombocytopenia in an Iranian Family

    Directory of Open Access Journals (Sweden)

    M Isadiar

    2006-06-01

    Full Text Available Objective: Thrombocytopenia is the most common hemostatic disease of the newborn. Inherited giant platelet syndromes are a heterogeneous group of rare bleeding disorders. In this paper we describe here a female neonate with autosomal dominant hereditary macrothrombocytopenia. Case report: A female neonate was referred to our center due to mucosal hemorrhage (nasal and gastrointestinal bleeding. Her mother’s platelet count was normal. However her father, paternal uncle and two paternal aunts also had severe thrombocytopenia and all of them underwent splenectomy for idiopathic thrombocytopenic purpura (ITP. Considering all clinical and laboratory findings, autosomal dominant hereditary macrothrombocytopenia was the best diagnosis. Conclusion: It is important to differentiate between congenital and acquired thrombocytopenia to avoid unneeded and potentially harmful therapy. Treatment is not usually necessary, however some patients with hereditary thrombocytopenia may benefit from bone marrow transplantation.

  17. Neuromyelitis optica antibody in Leber hereditary optic neuropathy: case report

    Directory of Open Access Journals (Sweden)

    Luciano Mesquita Simão

    2012-08-01

    Full Text Available Neuromyelitis optica antibody (or aquaporin-4 antibody is a well stablished serum marker associated to high-risk neuromyelitis optica syndrome that presents as an inflammatory demyelinating disease characterized by the occurrence of bilateral and simultaneous optic neuritis without complete visual recovery or it occurs as an isolated episode of transverse myelitis accompanied by longitudinally extensive spinal cord lesions. On the other hand, Leber hereditary optic neuropathy is a primarily hereditary disorder that affects all tissues of the body and its clinical presentation is tissue-specific for the optic nerve and, eventually, it might reach the spinal cord. Overlapping clinical features of neuromyelitis optica and Leber hereditary optic neuropathy may suggest common target organ diseases. The case report described herein emphasizes the coexistence of serum markers of both diseases, and suggests that further investigation of this challenging clinical presentation is warranted to confirm or rule out this association.

  18. Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

    International Nuclear Information System (INIS)

    Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

  19. Benefits and risks of danazol in hereditary angioedema

    DEFF Research Database (Denmark)

    Bork, Konrad; Bygum, Anette; Hardt, Jochen

    2008-01-01

    BACKGROUND: Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Treatment with androgens prevents attacks for those with this condition. OBJECTIVE: To examine the...... other patients, hereditary angioedema ran a mild course. The frequency of acute attacks during danazol treatment was reduced to 16.2%, and the attacks were considerably milder than before treatment. Laryngeal edema was reduced to 4.8%. Adverse effects (weight gain, virilization, menstrual irregularities...

  20. Hereditary angio-edema involving the gastrointestinal tract: CT findings

    International Nuclear Information System (INIS)

    We report a case of hereditary angio-edema in a young man presenting with recurrent abdominal pain for many years. The diagnosis was suspected on the basis of abdominal CT performed during an abdominal attack and was then confirmed by the measurement of serum concentration of C1 esterase inhibitor (C1-INH). To our knowledge, this is the first case reported of the hereditary form of angio-edema with isolated abdominal pain and in which the diagnosis was suggested by abdominal CT findings. (orig.)

  1. [Hereditary angioedema in childhood. Diagnosis and therapeutic challenges].

    Science.gov (United States)

    Pagnier, Anne

    2015-01-01

    Hereditary angioedema is a rare disease. In case of laryngeal edema or chronic abdominal pains, diagnosis is difficult in childhood because numerous differential diagnoses possibilities are to be considered. The diagnosis of hereditary angioedema with normal C1Inh (type III) is also a challenge because it is based only on clinical features. Important school absenteeism can be due to recurrent abdominal attacks. Early diagnosis, specific management, and therapeutic education are necessary for improvement of quality of life. Actually, subcutaneous treatment is not yet available for children. Studies are going on. In the meantime, C1Inh concentrate intravenous administration must be available for children quickly and safely. PMID:25511651

  2. Hereditary benign telangiectasia without family history in China

    Institute of Scientific and Technical Information of China (English)

    CAI Lin; SUN Qing-miao; ZANG Dong-jie; ZHANG Jian-zhong

    2011-01-01

    A case of hereditary benign telangiectasia without family history was reported. A 39-year-old woman presented with small and tiny telangiectases on the face, neck, upper trunk and forearms at birth. The numbers and sizes of the lesions increased gradually and she had no hemorrhagic diathesis and systemic diseases. No similar patients were found in her family. Upon physical examination, telangiectases were found on the face, neck, upper trunk and forearms; and a telangiectatic erythema was found on the right forearm 25 mm ×40 mm in size. Histopathology examination showed a normal epidermis and dilation of the capillaries at upper dermis. Hereditary benign telangiectasia without family history was diagnosed.

  3. Mutator gene and hereditary non-polyposis colorectal cancer

    Science.gov (United States)

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.

    2008-02-05

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  4. Targeted therapy for hereditary cancer syndromes: hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial adenomatous polyposis, and Li-Fraumeni syndrome.

    Science.gov (United States)

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Cancer genetics has rapidly evolved in the last two decades. Understanding and exploring the several genetic pathways in the cancer cell is the foundation of targeted therapy. Several genomic aberrations have been identified and their role in carcinogenesis is being explored. In contrast to most cancers where these mutations are acquired, patients with hereditary cancer syndromes have inherited genomic aberrations. The understanding of the molecular pathobiology in hereditary cancer syndromes has advanced dramatically. In addition, many molecularly targeted therapies have been developed that could have potential roles in the treatment of patients with hereditary cancer syndromes. In this review, we outline the presentation, molecular biology, and possible targeted therapies for two of the most widely recognized hereditary cancer syndromes -- hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colorectal cancer syndrome (Lynch syndrome). We will also discuss other syndromes such as familial adenomatous polyposis and Li-Fraumeni syndrome (TP53). PMID:25549704

  5. Genetics Home Reference: hereditary sensory and autonomic neuropathy type IE

    Science.gov (United States)

    ... of the neurons that make up the nervous system. However, it is not known how the mutations cause the specific signs and symptoms of HSAN IE. Learn more about the gene associated with hereditary sensory and autonomic neuropathy type IE DNMT1 Related Information ...

  6. Hereditary hemochromatosis and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Ellervik, Christina; Tybjaerg-Hansen, Anne; Grande, Peer;

    2005-01-01

    BACKGROUND: We tested the hypothesis that the hereditary hemochromatosis genotypes C282Y/C282Y, C282Y/H63D, or C282Y/wild-type are risk factors for ischemic heart disease (IHD) and myocardial infarction (MI). METHODS AND RESULTS: We performed a prospective study of 9178 individuals from the Danish...

  7. Dementia with non-hereditary cystatin C angiopathy

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Jóhannesson, G;

    1989-01-01

    Brain biopsies from two patients with non-hereditary cerebral hemorrhages and eighty autopsied cases with the clinical diagnosis of dementia are presented. The biopsied cases, both males aged 64 and 59, had a sudden onset of cerebral hemorrhage, mild progressive dementia and cystatin C cerebral...

  8. On the many faces of Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, RJ; Tijmes, NT; Cobben, JM; Bolhuis, PA; vanNesselrooij, BPM; Houtman, WA; deKokNazaruk, MM; BleekerWagemakers, EM

    1997-01-01

    Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between t

  9. RB1 mutations and second primary malignancies after hereditary retinoblastoma

    NARCIS (Netherlands)

    Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

    2012-01-01

    Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199 survivo

  10. Genetics and ionizing radiations. 1. Genetics and hereditary diseases

    International Nuclear Information System (INIS)

    The desoxyribonucleic acid (DNA) is the chemical vehicle of heredity. Each hereditary character is determined by a short segment of the DNA molecule called gene. Gene operations are governed by regulating systems. The DNA is located in the chromosomes, easily analysed by light microscopy. The chromosome number and form are fairly characteristic of a species. Ours has 46 chromosomes, i.e. 23 pairs. Anomalies of the hereditary stock can be qualitative: affecting one gene they are expressed by diversely serious diseases. They can be quantitative and bear on the lack or excess of a chromosome or a segment of chromosome; most often, resulting diseases are very serious; Downs's syndrome is a well-known example. The various modes of transmission of these hereditary characters are analysed. The change of a chromosome or a gene from a normal to an abnormal form is called a mutation. It occurs scarcely, but the effects of mutations accumulate. At birth, nearly 10% of children should have one abnormal hereditary character at least, however most of these characters do not induce a true disease. Anomalies are more frequent at conception, many abnormal embryos or foetuses being aliminated by miscarriages

  11. Longitudinal Cerebral Blood Flow Changes during Speech in Hereditary Ataxia

    Science.gov (United States)

    Sidtis, John J.; Strother, Stephen C.; Naoum, Ansam; Rottenberg, David A.; Gomez, Christopher

    2010-01-01

    The hereditary ataxias constitute a group of degenerative diseases that progress over years or decades. With principal pathology involving the cerebellum, dysarthria is an early feature of many of the ataxias. Positron emission tomography was used to study regional cerebral blood flow changes during speech production over a 21 month period in a…

  12. Genetics Home Reference: hereditary sensory and autonomic neuropathy type II

    Science.gov (United States)

    ... article on PubMed Central Huang CL, Kuo E. Mechanisms of disease: WNK-ing at the mechanism of salt-sensitive hypertension. Nat Clin Pract Nephrol. ... Verpoorten N, De Jonghe P, Timmerman V. Disease mechanisms in hereditary sensory and autonomic neuropathies. Neurobiol Dis. ...

  13. Guidelines for the genetic diagnosis of hereditary recurrent fevers

    DEFF Research Database (Denmark)

    Shinar, Y; Obici, L; Aksentijevich, I;

    2012-01-01

    Hereditary recurrent fevers (HRFs) are a group of monogenic autoinflammatory diseases characterised by recurrent bouts of fever and serosal inflammation that are caused by pathogenic variants in genes important for the regulation of innate immunity. Discovery of the molecular defects responsible...

  14. Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Kjeldsen, J

    2000-01-01

    Gastrointestinal bleeding occurs in a number of patients with hereditary hemorrhagic telangiectasia (HHT) and may lead to a high transfusion need. The aim of this study was to estimate the occurrence and severity of gastrointestinal bleeding in a geographically well defined HHT population....

  15. Efficiency of laser treatment in patients with hereditary hemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Jørgensen, Gita; Lange, Bibi; Wanscher, Jens Højberg;

    2011-01-01

    Earlier studies have shown the effect of laser treatment on epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). At the present time, only very few prospective trials have been performed, and many studies are based on patients' subjective assessment of the severity of epistaxis...

  16. National mutation study among Danish patients with hereditary haemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Tørring, P M; Brusgaard, K; Ousager, L B;

    2014-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominantly inherited vascular disease characterized by the presence of mucocutaneous telangiectasia and visceral arteriovenous malformations (AVM). The clinical diagnosis of HHT is based on the Curaçao criteria. About 85% of HHT patients...

  17. Study of glycolytic intermediates in hereditary elliptocytosis with thalassemia

    Directory of Open Access Journals (Sweden)

    Pavri Roshan

    1977-01-01

    Full Text Available Glycolytic intermediates like ATP, DPG and GSH have been studied in a family with. hereditary elliptocytosis and thalassemia. Results indicate a fall in ATP with a concomitant rise in DPG in the Patient. Findings are discussed in relation to other data.

  18. McCune-Albright syndrome

    Science.gov (United States)

    ... bones in the face Gigantism Irregular, large patchy cafe-au-lait spots , especially on the back ... Acromegaly Adrenal abnormalities Gigantism Hyperparathyroidism Hyperthyroidism Hypophosphatemia Large cafe-au-lait spots on the skin Liver disease, ...

  19. New treatments addressing the pathophysiology of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Davis Alvin E

    2008-04-01

    Full Text Available Abstract Hereditary angioedema is a serious medical condition caused by a deficiency of C1-inhibitor. The condition is the result of a defect in the gene controlling the synthesis of C1-inhibitor, which regulates the activity of a number of plasma cascade systems. Although the prevalence of hereditary angioedema is low – between 1:10,000 to 1:50,000 – the condition can result in considerable pain, debilitation, reduced quality of life, and even death in those afflicted. Hereditary angioedema presents clinically as cutaneous swelling of the extremities, face, genitals, and trunk, or painful swelling of the gastrointestinal mucosa. Angioedema of the upper airways is extremely serious and has resulted in death by asphyxiation. Subnormal levels of C1-inhibitor are associated with the inappropriate activation of a number of pathways – including, in particular, the complement and contact systems, and to some extent, the fibrinolysis and coagulation systems. Current findings indicate bradykinin, a product of contact system activation, as the primary mediator of angioedema in patients with C1-inhibitor deficiency. However, other systems may play a role in bradykinin's rapid and excessive generation by depleting available levels of C1-inhibitor. There are currently no effective therapies in the United States to treat acute attacks of hereditary angioedema, and currently available agents used to treat hereditary angioedema prophylactically are suboptimal. Five new agents are, however, in Phase III development. Three of these agents replace C1-inhibitor, directly addressing the underlying cause of hereditary angioedema and re-establishing regulatory control of all pathways and proteases involved in its pathogenesis. These agents include a nano-filtered C1-inhibitor replacement therapy, a pasteurized C1-inhibitor, and a recombinant C1-inhibitor isolated from the milk of transgenic rabbits. All C1-inhibitors are being investigated for acute angioedema

  20. New treatments addressing the pathophysiology of hereditary angioedema.

    Science.gov (United States)

    Davis, Alvin E

    2008-01-01

    Hereditary angioedema is a serious medical condition caused by a deficiency of C1-inhibitor. The condition is the result of a defect in the gene controlling the synthesis of C1-inhibitor, which regulates the activity of a number of plasma cascade systems. Although the prevalence of hereditary angioedema is low - between 1:10,000 to 1:50,000 - the condition can result in considerable pain, debilitation, reduced quality of life, and even death in those afflicted. Hereditary angioedema presents clinically as cutaneous swelling of the extremities, face, genitals, and trunk, or painful swelling of the gastrointestinal mucosa. Angioedema of the upper airways is extremely serious and has resulted in death by asphyxiation.Subnormal levels of C1-inhibitor are associated with the inappropriate activation of a number of pathways - including, in particular, the complement and contact systems, and to some extent, the fibrinolysis and coagulation systems.Current findings indicate bradykinin, a product of contact system activation, as the primary mediator of angioedema in patients with C1-inhibitor deficiency. However, other systems may play a role in bradykinin's rapid and excessive generation by depleting available levels of C1-inhibitor.There are currently no effective therapies in the United States to treat acute attacks of hereditary angioedema, and currently available agents used to treat hereditary angioedema prophylactically are suboptimal. Five new agents are, however, in Phase III development. Three of these agents replace C1-inhibitor, directly addressing the underlying cause of hereditary angioedema and re-establishing regulatory control of all pathways and proteases involved in its pathogenesis. These agents include a nano-filtered C1-inhibitor replacement therapy, a pasteurized C1-inhibitor, and a recombinant C1-inhibitor isolated from the milk of transgenic rabbits. All C1-inhibitors are being investigated for acute angioedema attacks; the nano-filtered C1

  1. The skull in renal osteodystrophy

    International Nuclear Information System (INIS)

    Skull X-ray of 60 patients with chronic renal failure were examined. Alterations included diminished or increased bone density, radiolucent areas, pepper pot skull and the disappearance of vascular grooves and sutures. It is suggested that the radiological aspect of the skull is of very little diagnostic use in the assessment of uremic osteopathy since specific alterations are rare and tardive and show no correlation with clinical and laboratory findings. Skull X-ray can be usefull in assessing the effects of treatment (vitamin D derivaties, parathyroidectomy) and for the identification of focal lesions (brown tumors)

  2. Genetic mutations, diagnostic methods, and therapies related to hereditary haemochromatosis

    Directory of Open Access Journals (Sweden)

    Karina Marini Aguiar

    2014-03-01

    Full Text Available Hereditary haemochromatosis is a genetic disease related to various iron metabolism disorders and a major cause of iron overload. The technical and scientific advances obtained over the last decades, particularly with the development of molecular biology, have contributed to greater knowledge on iron metabolism and the main factors related to its regulation, as well as the disorders that can result in deficit or overload. The identification of some genes and their mutations has helped to understand the regulatory mechanisms responsible for maintaining the homeostasis of such an essential mineral for several biochemical processes. Thus, this review addresses aspects related to iron, its metabolism and the causes for overload, particularly that deriving from hereditary haemochromatosis. Also with regard to this disease, we present diagnosis, guidance on treatment, and most frequent mutations.

  3. Spinal Exostosis in a Boy with Multiple Hereditary Exostoses

    Directory of Open Access Journals (Sweden)

    Ali Al Kaissi

    2013-01-01

    Full Text Available We report on a 13-year-old boy who presented with multiple hereditary exostosis and had development of back pain, associated with neurological deficits, and was found to have exostoses in the spinal canal. Spine radiograph showed a cauliflower-like abnormality of multiple exostoses of the posterior arch (pedicle of the thoracic vertebrae (T3–5. Reformatted CT scanning revealed the simultaneous development of intra- and extraspinal osteochondromatosis of T3–5. The spinal cord was compressed by the intraspinal exostosis. Our patient was surgically treated for intraspinal exostoses and showed cessation of neurological deficits. We report what might be a rare association of spinal cord compression in a patient with multiple hereditary exostoses.

  4. Cardiac arrest due to airway obstruction in hereditary angioedema.

    Science.gov (United States)

    Fuse, Takashi; Nakada, Taka-aki; Taniguchi, Masashi; Mizushima, Yasuaki; Matsuoka, Tetsuya

    2015-12-01

    Hereditary angioedema (HAE) is a rare genetic disease caused by a deficiency of functional C1 esterase inhibitor that causes swelling attacks in various body tissues. We hereby report a case of out-of-hospital cardiac arrest due to airway obstruction in HAE. Cutaneous swelling and abdominal pain attacks caused by gastrointestinal wall swelling are common symptoms in HAE, whereas laryngeal swelling is rare. Emergency physicians may have few chances to experience cases of life-threatening laryngeal edema resulting in a delay from symptom onset to the diagnosis of HAE. Hereditary angioedema is diagnosed by performing complement blood tests. Because safe and effective treatment options are available for the life-threatening swellings in HAE, the diagnosis potentially reduces the risk of asphyxiation in patients and their blood relatives. PMID:25913082

  5. Hereditary anaemias: genetic basis, clinical features, diagnosis, and treatment*

    OpenAIRE

    1982-01-01

    The hereditary anaemias present a major genetic health problem that contributes considerably to childhood mortality and morbidity in many developing countries. This article summarizes recent scientific and technical advances in knowledge concerning the genes involved and their interaction to produce major haemoglobinopathies, the clinical pictures of these conditions, and their diagnostic criteria. Though there is no definitive cure, supportive treatment for the haemoglobinopathies has improv...

  6. HEREDITARY INTRAVENTRICULAR CONDUCTION DISORDERS IN THE FAMILY FROM KRASNOYARSK

    Directory of Open Access Journals (Sweden)

    A. A. Chernova

    2016-01-01

    Full Text Available Pedigree of the family from Krasnoyarsk city with hereditary disorders of intracardiac conduction was studied. The diagnosis of each family member was verified by electrocardiography (ECG, echocardiography , bicycle ergometry , ECG Holter monitoring. The family 10-year follow-up showed familial aggregation of intracardiac conduction disorders in grandson, niece, son of the proband niece, ie, in the III-degree relatives. Family history of III-degree relatives with intracardiac conduction disorders and discordant pathology is identified.

  7. Hereditary cancer risk assessment: essential tools for a better approach

    OpenAIRE

    Gomy, Israel; Estevez Diz, Maria Del Pilar

    2013-01-01

    Hereditary cancer risk assessment (HCRA) is a multidisciplinary process of estimating probabilities of germline mutations in cancer susceptibility genes and assessing empiric risks of cancer, based on personal and family history. It includes genetic counseling, testing and management of at-risk individuals so that they can make well-informed choices about cancer surveillance, surgical treatment and chemopreventive measures, including biomolecular cancer therapies. Providing patients and famil...

  8. Strumpellin and Spartin, Hereditary Spastic Paraplegia Proteins, are Binding Partners

    OpenAIRE

    Jiali Zhao; Peter Hedera

    2015-01-01

    Hereditary spastic paraplegia (HSP) is one of the most heterogeneous neurodegenerative diseases with more than 50 identified genes causing a relatively stereotypical phenotypic presentation. Recent studies of HSP pathogenesis have suggested the existence of shared biochemical pathways that are crucial for axonal maintenance and degeneration. We explored possible interactions of several proteins associated with this condition. Here we report interactions of endogenous and overexpressed strumpe...

  9. Hereditary Colorectal Cancer: Registration, Screening and Prognostic Biomarker Analysis

    OpenAIRE

    Barrow, Paul

    2015-01-01

    Aims: The purpose of the research was to investigate the benefits of a hereditary colorectal cancer registry in the management of patients and families with Lynch syndrome. In study one, a systematic review was performed to quantify the impact of registration and screening on colorectal cancer (CRC) incidence and mortality, with comparison between familial adenomatous polyposis (FAP) and Lynch syndrome (LS). In study two, a regional Lynch syndrome registry was utilised to evaluate the uptake ...

  10. Hereditary spastic paraplegia with a thin corpus callosum

    Energy Technology Data Exchange (ETDEWEB)

    Somasundaram, Sivaraman; Kesavadas, Chandrasekharan [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Imaging Sciences and Interventional Radiology, Trivandrum (India); Raghavendra, Seetharam; Singh, Atampreet; Nair, Muraleedharan [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Neurology, Trivandrum (India)

    2007-05-15

    We report a 15-year-old boy with autosomal recessive complicated hereditary spastic paraplegia with a thin corpus callosum (HSP-TCC). The involvement of the corpus callosum was characteristic with the genu and body predominantly affected with relative sparing of the splenium. HSP-TCC is being increasingly recognized over a wider geographical area than earlier believed. We now report a case of HSP-TCC from the Indian subcontinent. (orig.)

  11. Hereditary hemochromatosis in an Indian origin: A rare case report

    OpenAIRE

    R L Geetha; Vani, B. R.; V Srinivasa Murthy; Deepak Kumar; Geethamala, K.

    2015-01-01

    Hereditary hemochromatosis (HH) is manifested as an iron overload in different organs due to homozygosity of a single autosomal mutation. If untreated it leads to conditions such as liver cirrhosis, type 1 diabetes mellitus, hypogonadotropic hypogonadism, cardiomyopathy, arthritis, and bronze coloring of the skin. Hemochromatosis affects as many as 1 in every 200 people in the United States, but in India the reports of genetic study are rare and virtually unexplored. It is also possible that ...

  12. Hereditary hemochromatosis:with a special emphasis on HFE genotyping

    OpenAIRE

    Hannuksela, J. (Jokke)

    2004-01-01

    Abstract Hereditary hemochromatosis (HH) is a common autosomal recessive disorder estimated to affect one out of every 250–400 Caucasian individuals. It is a disorder of iron metabolism, in which excessive iron accumulation in the body may induce serious clinical manifestations (e.g. liver cirrhosis, hepatocellular carcinoma, diabetes, and cardiomyopathy). HH is caused by mutations in the HFE gene, and HFE genotyping thus enables early diagnosis of the disease and detection of the individu...

  13. Hereditary Amyloid Cardiomyopathy Caused by a Variant Apolipoprotein A1

    OpenAIRE

    Hamidi Asl, Ladan; Liepnieks, Juris J.; Hamidi Asl, Kamran; Uemichi, Tomoyuki; Moulin, Georges; Desjoyaux, Emmanuel; Loire, Robert; Delpech, Marc; Grateau, Gilles; Benson, Merrill D.

    1999-01-01

    Autosomal dominant hereditary amyloidosis with a unique cutaneous and cardiac presentation and death from heart failure by the sixth or seventh decade was found to be associated with a previously unreported point mutation (thymine to cytosine, nt 1389) in exon 4 of the apolipoprotein A1 (apoA1) gene. The predicted substitution of proline for leucine at amino acid position 90 was confirmed by structural analysis of amyloid protein isolated from cardiac deposits of amyloid. The subunit protein ...

  14. Cardiac function in hereditary transthyretin amyloidosis : an echocardiographic study

    OpenAIRE

    Arvidsson, Sandra

    2016-01-01

    Background: Hereditary transthyretin amyloidosis (ATTR) is a lethal disease in which misfolded transthyretin (TTR) proteins accumulate as insoluble aggregates in tissues throughout the body. A common mutation is the exchange of valine to methionine at place 30 (TTR V30M), a form endemically found in the northern parts of Sweden. The main treatment option for ATTR amyloidosis is liver transplantation as the procedure halts production of mutated transthyretin. The disease is associated with mar...

  15. A Rare Cause of Abdominal Pain in Children: Hereditary Angioedema

    Directory of Open Access Journals (Sweden)

    Deniz Özçeker

    2015-03-01

    Full Text Available Hereditary angioedema (HA is a rare, autosomal-dominant genetic disorder presenting with recurrent attacks of angioedema. The most commonly involved organs include the extremites, face, neck, upper respiratory tract, genital region and the gastrointestinal tract. Edema of the intestinal mucosa can cause temporary obstruction and severe abdominal pain that can be confused with acute abdomen. Pediatricians and emergency physicians should keep in mind this rare disease in the differential diagnosis of severe abdominal pain.

  16. Hereditary spastic paraplegia with a thin corpus callosum

    International Nuclear Information System (INIS)

    We report a 15-year-old boy with autosomal recessive complicated hereditary spastic paraplegia with a thin corpus callosum (HSP-TCC). The involvement of the corpus callosum was characteristic with the genu and body predominantly affected with relative sparing of the splenium. HSP-TCC is being increasingly recognized over a wider geographical area than earlier believed. We now report a case of HSP-TCC from the Indian subcontinent. (orig.)

  17. Hereditary hemorrhagic telangiectasia and juvenile polyposis: an overlap of syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Poletto, Erica D.; Levin, Terry L. [Montefiore Medical Center, Department of Radiology, Bronx, NY (United States); Trinh, Angela M. [Albert Einstein College of Medicine, Bronx, NY (United States); Loizides, Anthony M. [Children' s Hospital at Montefiore, Department of Pediatric Gastroenterology, Bronx, NY (United States)

    2010-07-15

    Hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu syndrome) is a syndrome characterized by multiorgan telangiectases and arteriovenous malformations. A subset of patients with a mutation in the MADH4 gene on chromosome 18 exhibits an overlapping syndrome of HHT and juvenile polyposis (JPS). We present one such family. Genetic testing is warranted when either HHT or JPS is diagnosed, as early recognition of this syndrome overlap allows appropriate management of these patients. (orig.)

  18. Usefulness of erythrocyte ferritin analysis in hereditary hemochromatosis.

    OpenAIRE

    Cruickshank, M K; Ninness, J; A. Curtis; Barr, R M; Flanagan, P R; Ghent, C N; Valberg, L. S.

    1987-01-01

    A study was carried out to determine the usefulness of erythrocyte ferritin analysis in identifying homozygotes and heterozygotes in families affected with hereditary hemochromatosis, an autosomal recessive disorder. To select the subjects the genotypes of 60 people from 26 affected families were determined by HLA-A and HLA-B haplotyping. In addition, data for 12 homozygotes for whom erythrocyte ferritin values were available from the literature were included. Likelihood analysis was used to ...

  19. Hereditary angioedema: quality of life in Brazilian patients

    Directory of Open Access Journals (Sweden)

    Maria Abadia Consuelo M. S. Gomide

    2013-01-01

    Full Text Available OBJECTIVE: Hereditary angioedema is a serious medical condition caused by a rare autosomal dominant genetic disorder and it is associated with deficient production or dysfunction of the C1 esterase inhibitor. In most cases, affected patients experience unexpected and recurrent crises of subcutaneous, gastrointestinal and laryngeal edema. The unpredictability, intensity and other factors associated with the disease impact the quality of life of hereditary angioedema patients. We evaluated the quality of life in Brazilian hereditary angioedema patients. METHODS: Patients older than 15 years with any severity of hereditary angioedema and laboratory confirmation of C1 inhibitor deficiency were included. Two questionnaires were used: a clinical questionnaire and the SF-36 (a generic questionnaire. This protocol was approved by the Ethics Committee of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTS: The SF-36 showed that 90.4% (mean of all the patients had a score below 70 and 9.6% had scores equal to or higher than 70. The scores of the eight dimensions ranged from 51.03 to 75.95; vitality and social aspects were more affected than other arenas. The internal consistency of the evaluation was demonstrated by a Cronbach's alpha value above 0.7 in seven of the eight domains. CONCLUSIONS: In this study, Brazilian patients demonstrated an impaired quality of life, as measured by the SF-36. The most affected domains were those related to vitality and social characteristics. The generic SF-36 questionnaire was relevant to the evaluation of quality of life; however, there is a need for more specific instruments for better evaluation.

  20. Hereditary nonsyndromic gingival fibromatosis: report of family case series.

    Science.gov (United States)

    Peeran, Syed Wali; Ramalingam, Karthikeyan; Peeran, Syed Ali; Mugrabi, Marei Hamed; Abdulla, Khaled Awidat

    2013-01-01

    Hereditary gingival fibromatosis (HGF) is a rare, benign disorder with slowly progressive enlargement of maxillary and mandibular gingiva. Herewith, we report the first case series of HGF presenting among mother and all of her 3 children. Their complaints included unaesthetic appearance due to gingival growth, malocclusion, and difficulty in mastication. Conventional gingivectomy with oral hygiene measures and regular followup is the treatment of choice for such presentation. PMID:24191204

  1. Hereditary Nonsyndromic Gingival Fibromatosis: Report of Family Case Series

    OpenAIRE

    Syed Wali Peeran; Karthikeyan Ramalingam; Syed Ali Peeran; Marei Hamed Mugrabi; Khaled Awidat Abdulla

    2013-01-01

    Hereditary gingival fibromatosis (HGF) is a rare, benign disorder with slowly progressive enlargement of maxillary and mandibular gingiva. Herewith, we report the first case series of HGF presenting among mother and all of her 3 children. Their complaints included unaesthetic appearance due to gingival growth, malocclusion, and difficulty in mastication. Conventional gingivectomy with oral hygiene measures and regular followup is the treatment of choice for such presentation.

  2. One novel transcript of human hereditary multipleexostoses 2 (EXT2)

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The encoding sequence of human hereditary multiple exostoses gene EXT2.1 is 30 bp longer than EXT2, and they differ in a sequence of 90 base pairs. In order to clarify EXT2.1 structure, this 90 bp sequence was analyzed with the Human Sequence Draft, a database provided by Celera Genomics. The result shows that EXT2.1 is a novel transcript of EXT2 gene, suggesting a rare event of alternative splicing.

  3. [Familial brain abscess as a complication of hereditary hemorrhagic telangiectasia].

    Science.gov (United States)

    Szöts, M; Szapáry, L; Nagy, F; Vetö, F

    2001-10-21

    The hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) is an inherited autosomal dominant disease with angiodysplasia of the skin, mucosa, parenchymal organs, and it can affect the central nervous system. In 40% of the cases neurological complications, most frequently intracerebral abscesses occur. In this study, the case history of a patient with central nervous system manifestation of hereditary hemorrhagic telangiectasia showing familiar aggregation of brain abscess will be presented. A young male patient was admitted to Neurological Department because of his first epileptic seizure and progressive right hemispheric symptoms. His examinations showed frontal abscess, which was surgically removed. The frequent nose-bleeding of the patient and recurrent brain abscess in his brother's history provided the possibility of hereditary hemorrhagic telangiectasia. The background of brain abscess were multiple pulmonary arteriovenous malformation, which were embolized by repeated angiography. Familiar brain abscess is very rare. However, in the case of brain abscess especially with familiarity diagnosis of the Rendu-Osler-Weber disease should be considered. PMID:11760648

  4. Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations.

    Science.gov (United States)

    Sijmons, Rolf H; Hofstra, Robert M W

    2016-02-01

    Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive Constitutional Mismatch Repair Deficiency syndrome. Both conditions are important to recognize clinically as their identification has direct consequences for clinical management and allows targeted preventive actions in mutation carriers. Lynch syndrome is one of the more common adult-onset hereditary tumor syndromes, with thousands of patients reported to date. Its tumor spectrum is well established and includes colorectal cancer, endometrial cancer and a range of other cancer types. However, surveillance for cancers other than colorectal cancer is still of uncertain value. Prophylactic surgery, especially for the uterus and its adnexa is an option in female mutation carriers. Chemoprevention of colorectal cancer with aspirin is actively being investigated in this syndrome and shows promising results. In contrast, the Constitutional Mismatch Repair Deficiency syndrome is rare, features a wide spectrum of childhood onset cancers, many of which are brain tumors with high mortality rates. Future studies are very much needed to improve the care for patients with this severe disorder. PMID:26746812

  5. Management of hereditary angioedema in pregnant women: a review

    Directory of Open Access Journals (Sweden)

    Caballero T

    2014-09-01

    Full Text Available Teresa Caballero,1,2 Julio Canabal,1 Daniela Rivero-Paparoni,1 Rosario Cabañas1 1Hospital La Paz Institute for Health Research, (IdiPaz 2Biomedical Research Network on Rare Diseases-U754 (CIBERER, Madrid, Spain Abstract: Three types of hereditary angioedema (HAE have been described: two are due to C1 inhibitor (C1-INH deficiency (C1-INH-HAE types I and II and one is characterized by normal C1-INH (nC1-INH-HAE. The management of pregnancy in patients with HAE is often a clinical challenge owing to potential worsening of the disease in relation to the physiological increase in estrogens and the limited treatment options. This review addresses the potential influence of pregnancy on the clinical severity of hereditary angioedema and the management of this disease during pregnancy with currently available treatments. Keywords: hereditary angioedema, pregnancy, female, treatment, C1 inhibitor concentrate, tranexamic acid

  6. An overview of novel therapies for acute hereditary angioedema.

    Science.gov (United States)

    Firszt, Rafael; Frank, Michael M

    2010-12-01

    Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance. Attacks are characterized by nonpitting edema of external or mucosal body surfaces. Patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can at times lead to asphyxiation. The disease is caused by a mutation in the gene encoding the complement C1-inhibitor protein, which leads to unregulated production of bradykinin. Long-term therapy has depended on the use of attenuated androgens or plasmin inhibitors but in the US there was, until recently, no specific therapy for acute attacks. As well, many patients with hereditary angioedema in the US were either not adequately controlled on previously available therapies or required doses of medications that exposed them to the risk of serious adverse effects. Five companies have completed or are currently conducting phase III clinical trials in the development of specific therapies to terminate acute attacks or to be used as prophylaxis. These products are based on either replacement therapy with purified plasma-derived or recombinant C1-inhibitor, or inhibition of the kinin-generating pathways with a recombinant plasma kallikrein inhibitor or bradykinin type 2 receptor antagonist. Published studies thus far suggest that all of these products are likely to be effective. These new therapies will likely lead to a totally new approach in treating hereditary angioedema. PMID:20866113

  7. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    OpenAIRE

    Bowen Tom; Cicardi Marco; Farkas Henriette; Bork Konrad; Longhurst Hilary J; Zuraw Bruce; Aygoeren-Pürsün Emel; Craig Timothy; Binkley Karen; Hebert Jacques; Ritchie Bruce; Bouillet Laurence; Betschel Stephen; Cogar Della; Dean John

    2010-01-01

    Abstract Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management...

  8. 2010 international consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    OpenAIRE

    Bowen, Tom; Cicardi, Marco; Farkas, Henriette; Bork, Konrad; Longhurst, Hilary J; Zuraw, Bruce; Aygören-Pürsün, Emel; Craig, Timothy; Binkley, Karen; Hebert, Jacques; Ritchie, Bruce; Bouillet, Laurence; Betschel, Stephen; Cogar, Della; Dean, John

    2010-01-01

    Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hered...

  9. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    OpenAIRE

    Bowen, Tom; Cicardi, Marco; Farkas, Henriette; Bork, Konrad; Longhurst, Hilary J; Zuraw, Bruce; Aygoeren-Pürsün, Emel; Craig, Timothy; Binkley, Karen; Hebert, Jacques; Ritchie, Bruce; Bouillet, Laurence; Betschel, Stephen; Cogar, Della; Dean, John

    2010-01-01

    Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hered...

  10. Colorectal Cancer Survivors' Interest in Genetic Testing for Hereditary Cancer: Implications for Universal Tumor Screening

    OpenAIRE

    Cragun, Deborah; Malo, Teri L.; Pal, Tuya; Shibata, David; Vadaparampil, Susan T

    2012-01-01

    Aims: Benefits of universal tumor screening for Lynch syndrome (LS), the most common form of hereditary colorectal cancer (CRC), will be realized only if patients are interested in genetic counseling and testing. This study explores interest in genetic testing for hereditary CRC among CRC patients who have never received genetic counseling or testing. Methods Using results from a cross-sectional survey of CRC patients (n=91) at varying categories of risk for hereditary CRC, bivariate and mult...

  11. Whole Exome Sequencing Identifies Multiple, Complex Etiologies in an Idiopathic Hereditary Pancreatitis Kindred

    OpenAIRE

    Jessica LaRusch; Sheila Solomon; M Michael Barmada; Whitcomb, David C

    2012-01-01

    Context Hereditary pancreatitis is the early onset form of chronic pancreatitis that is carried in an autosomal dominant pattern with variable penetrance. While 80% of hereditary pancreatitis has been shown to be due to a single mutation in the trypsinogen gene PRSS1, a number of hereditary pancreatitis families have no identified genetic cause for illness; thus no reliable screening options or clear therapy. Objective To explore the use of massive parallel DNA sequencing technology to discov...

  12. Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST mimicking hereditary GIST syndromes

    Directory of Open Access Journals (Sweden)

    Mafalda Costa Neves

    2015-01-01

    Conclusion: We describe a diffuse form of sporadic ICC hyperplasia harbouring multifocal GISTs, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes. Detection of somatic c-KIT exon 11 mutation ruled out a hereditary disorder.

  13. Hypogonadotropic hypogonadism associated with hereditary hemorrhagic telangiectasia [corrected].

    Science.gov (United States)

    Scarano, Valentina; Valentina, Scarano; De Santis, Daniele; Daniele, De Santis; Suppressa, Patrizia; Patrizia, Suppressa; Lastella, Patrizia; Patrizia, Lastella; Lenato, Gennaro Mariano; Mariano, Lenato Gennaro; Triggiani, Vincenzo; Vincenzo, Triggiani; Sabbà, Carlo; Carlo, Sabbà

    2013-01-01

    A 65-year-old man was referred to our clinic for the rehabilitation of right hemiparesis caused by ischaemic stroke. Hypertension, postphlebitic syndrome of lower limbs, frequent nose bleeding, and anemia were present in his history; in his adolescence, he was treated for idiopathic hypogonadotropic hypogonadism. Further investigations have revealed also microsomia, suggesting a clinical diagnosis of Kallmann syndrome, that is, an association, possible in males and females, of hypogonadotropic hypogonadism with olfactory deficits. A definite diagnosis of hereditary hemorrhagic telangiectasia was made based on clinical criteria and confirmed by genetic analysis. PMID:23710379

  14. Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia

    OpenAIRE

    MacKie Iain; McDonnell Sinead T; Barron Martin J; Dixon Michael J

    2008-01-01

    Abstract The hereditary dentine disorders, dentinogenesis imperfecta (DGI) and dentine dysplasia (DD), comprise a group of autosomal dominant genetic conditions characterised by abnormal dentine structure affecting either the primary or both the primary and secondary dentitions. DGI is reported to have an incidence of 1 in 6,000 to 1 in 8,000, whereas that of DD type 1 is 1 in 100,000. Clinically, the teeth are discoloured and show structural defects such as bulbous crowns and small pulp cham...

  15. Repetitive Transcranial Magnetic Stimulation in Patients with Hereditary Spastic Paraplegia

    Directory of Open Access Journals (Sweden)

    Mehmet Ağırman

    2011-06-01

    Full Text Available Hereditary spastic paraplegia (HSPP is a heterogeneous genetic disease characterized by progressive spasticity of lower extremities. Spasticity is a major cause of long-term disability in HSPP and significantly affects the functional life of patients. Repetitive transcranial magnetic stimulation (rTMS is widely used in diagnosis and treatment of many neurological and psychiatric diseases. Although the positive impacts of rTMS for spasticity have been reported, no study has been found on HSPP. We present two HSPP patients treated with low frequency rTMS (20 minutes at a frequency of 1 Hz (1200 pulses, for a period of 10 treatment sessions.

  16. Genetic heterogeneity in families with hereditary multiple exostoses

    OpenAIRE

    Cook, April; Raskind, Wendy; Blanton, Susan Halloran; Pauli, Richard M.; Gregg, Ronald G.; Francomano, Claire A.; Puffenberger, Eric; Conrad, Ernest U.; Schmale, Gregory; Schellenberg, Gerard; Wijsman, Ellen; Hecht, Jacqueline T.; Wells, Dan; Wagner, Michael J.

    1993-01-01

    We have carried out a linkage analysis on 11 families segregating gene(s) for hereditary multiple exostoses (EXT). Four highly informative, short tandem-repeat (STR) markers that have been physically mapped to an interval surrounding the Langer-Giedion chromosomal region (8q24.11-q24.13) were used in a multipoint linkage analysis. Significant evidence for linkage of EXT with genetic heterogeneity was found. A model of heterogeneity with linkage of the disease gene to the STR markers in 70% of...

  17. Colonoscopy and chromoscopy in hereditary colorectal cancer syndromes.

    Science.gov (United States)

    Jenkins Wessling, Erin; Lanspa, Stephen J

    2016-07-01

    With hereditary colorectal cancer prevention studies it is difficult to demonstrate reduced mortality. Large populations are needed with well characterized genetics followed over a long period of time. Those studies do exist for standard white light colonoscopy surveillance in Lynch syndrome, but not for newer technologies including chromoscopy. For these newer technologies adenoma detection rate becomes the stand-in for mortality, and the assumption is made that surveillance efficacy impacts cancer occurrence. Though well-designed and important work exists in this area, the data do not support firm conclusions regarding the use of chromoscopy in Lynch syndrome. PMID:26892866

  18. Angioedema hereditario en pediatría Hereditary pediatric angioedema

    Directory of Open Access Journals (Sweden)

    A. Calvo Gómez-Rodulfo

    2009-01-01

    Full Text Available

    Introducción: El angioedema hereditario es una patología de origen genético causada por la alteración del gen que codifica la proteína inhibidora de la C1 esterasa activada (C1-INH. La prevalencia de esta entidad es baja, lo que dificulta su diagnóstico y manejo adecuado.
    Caso clínico: Se presenta el caso de una paciente con episodios repetidos de edema subcutáneo localizado en las extremidades desde los tres años de vida, añadiendo disfagia y disfonía a partir de la pubertad. Su madre y un hermano presentaban sintomatología similar. En los tres casos se demostró deficiencia de C1-INH, siendo diagnosticados de angioedema hereditario.
    Conclusiones: El angioedema hereditario es una entidad poco frecuente y potencialmente grave. Aunque la sintomatología puede ser similar a cuadros alérgicos y anafilácticos, el manejo es muy diferente, siendo la administración intravenosa de C1-INH de elección en el tratamiento del episodio agudo grave. Debe considerarse también la necesidad de tratamiento profiláctico a largo plazo ante el antecedente de episodio de angioedema grave o cuando los episodios se repitan frecuentemente. En este artículo se revisan los distintos aspectos diagnósticos y terapéuticos del angioedema hereditario.

    Introduction: The hereditary angioedema is a rare genetical disease caused by deficiency of C1 esterase inhibitor (C1-INH. The diagnosis is difficult because the low prevalence f it.
    Clinical report: We show a female with recurrent episodes of edema in extremities since 3 years old, with dysphagia and voice change since puberty. Her mother and brother had similar manifestations. All they were diagnosed of hereditary angioedema with C1-INH deficiency.
    Conclusions: The hereditary angioedema is a rare and potential severe disease. Its manifestations may be similar to the allergy or anaphylaxis, but its treatment is different. Emergency therapy of acute oedematous attacks with C1

  19. Intragenic Duplication A Novel Mutational Mechanism in Hereditary Pancreatitis

    DEFF Research Database (Denmark)

    Joergensen, M. T.; Geisz, A.; Brusgaard, K.;

    2011-01-01

    cationic trypsinogen (p.K23_I24insIDK). The aim of the present study was to characterize the effect of this unique genetic alteration on the function of human cationic trypsinogen. METHODS: Wild-type and mutant cationic trypsinogens were produced recombinantly and purified to homogeneity. Trypsinogen...... autoactivation. Activation by human cathepsin B also was accelerated by 10-fold. Secretion of the p.K23_I24insIDK mutant from transfected cells was diminished, consistent with intracellular autoactivation. CONCLUSIONS: This is the first report of an intragenic duplication within the PRSS1 gene causing hereditary...

  20. Comprehensive mutational screening in a cohort of Danish families with hereditary congenital cataract

    DEFF Research Database (Denmark)

    Hansen, Lars; Mikkelsen, Annemette; Nürnberg, Peter;

    2009-01-01

    PURPOSE: Identification of the causal mutations in 28 unrelated families and individuals with hereditary congenital cataract identified from a national Danish register of hereditary eye diseases. Seven families have been published previously, and the data of the remaining 21 families are presented...

  1. An effect from anticipation also in hereditary nonpolyposis colorectal cancer families without identified mutations

    DEFF Research Database (Denmark)

    Timshel, Susanne; Therkildsen, Christina; Bendahl, Pär-Ola; Bernstein, Inge; Nilbert, Mef

    Optimal prevention of hereditary cancer is central and requires initiation of surveillance programmes and/or prophylactic measures at a safe age. Anticipation, expressed as an earlier age at onset in successive generations, has been demonstrated in hereditary nonpolyposis colorectal cancer (HNPCC...

  2. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    DEFF Research Database (Denmark)

    Bowen, Tom; Cicardi, Marco; Farkas, Henriette;

    2010-01-01

    ABSTRACT: BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 ...

  3. Chromosome damage in G0 X-irradiated lymphocytes from patients with hereditary retinoblastoma

    International Nuclear Information System (INIS)

    The amount of chromosome damage in peripheral blood lymphocytes following 400 rads G0 X-irradiation in 10 of 11 hereditary retinoblastoma patients was shown to be intermediate between that in normals and damage in trisomy 21 patients. The difference between normals and hereditary retinoblastoma patients was small, it varied between hereditary retinoblastoma patients, and no difference was detected following 200 rads G0 X-irradiation. No difference was found in levels of spontaneous chromosome damage in hereditary retinoblastoma patients, trisomy 21 patients, and normals. These results suggest that, although sensitivity to ionizing radiation may be associated with hereditary retinoblastoma, the observed difference is so small that it is probably not the major effect of the gene predisposing to retinoblastoma

  4. Age-related penetrance of hereditary atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Sullivan, Maren; Rybicki, Lisa A; Winter, Aurelia; Hoffmann, Michael M; Reiermann, Stefanie; Linke, Hannah; Arbeiter, Klaus; Patzer, Ludwig; Budde, Klemens; Hoppe, Bernd; Zeier, Martin; Lhotta, Karl; Bock, Andreas; Wiech, Thorsten; Gaspert, Ariana; Fehr, Thomas; Woznowski, Magdalena; Berisha, Gani; Malinoc, Angelica; Goek, Oemer-Necmi; Eng, Charis; Neumann, Hartmut P H

    2011-11-01

    Hereditary atypical hemolytic uremic syndrome (aHUS), a dramatic disease frequently leading to dialysis, is associated with germline mutations of the CFH, CD46, or CFI genes. After identification of the mutation in an affected aHUS patient, single-site gene testing of relatives is the preventive care perspective. However, clinical data for family counselling are scarce. From the German-Speaking-Countries-aHUS-Registry, 33 index patients with mutations were approached for permission to offer relatives screening for their family-specific mutations and to obtain demographic and clinical data. Mutation screening was performed using direct sequencing. Age-adjusted penetrance of aHUS was calculated for each gene in index cases and in mutation-positive relatives. Sixty-one relatives comprising 41 parents and 20 other relatives were enrolled and mutations detected in 31/61. In total, 40 research participants had germline mutations in CFH, 19 in CD46 and in 6 CFI. Penetrance at age 40 was markedly reduced in mutation-positive relatives compared to index patients overall with 10% versus 67% (P < 0.001); 6% vs. 67% (P < 0.001) in CFH mutation carriers and 21% vs. 70% (P= 0.003) in CD46 mutation carriers. Age-adjusted penetrance for hereditary aHUS is important to understand the disease, and if replicated in the future, for genetic counselling. PMID:21906045

  5. Burden of Illness in Hereditary Angioedema: A Conceptual Model.

    Science.gov (United States)

    Bygum, Anette; Aygören-Pürsün, Emel; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Wait, Suzanne; Boysen, Henrik B; Caballero, Teresa

    2015-07-01

    The objective of the Hereditary Angioedema Burden of Illness Study in Europe was to assess the real-world experience of hereditary angioedema (HAE) from the patient perspective. Based on open-ended qualitative interviews with 30 patients from Spain, Germany and Denmark, 5 key themes emerged characterizing the impact of HAE on health-related quality of life (HRQoL): (i) unnecessary treatments and procedures, (ii) symptom triggers, (iii) attack impacts, (iv) caregiver impacts, and (v) long-term impacts. Patients for example experience unnecessary medical procedures due to diagnostic delays; anxiety and fear about attacks, and passing HAE to children; reduced work/school productivity; and limited career/educational achievement. Patient caregivers also experience worry and work/activity interruption during the attacks. In conclusion, a conceptual model was developed illustrating the hypothesized relationships among the wide-ranging short- and long-term HRQoL impacts of HAE. These findings can be used to highlight important issues in clinical management, raise awareness of the patients' experience among policymakers and help guide measurement of HRQoL outcomes in future studies in HAE. PMID:25394853

  6. Fractional hereditariness of lipid membranes: Instabilities and linearized evolution.

    Science.gov (United States)

    Deseri, L; Pollaci, P; Zingales, M; Dayal, K

    2016-05-01

    In this work lipid ordering phase changes arising in planar membrane bilayers is investigated both accounting for elasticity alone and for effective viscoelastic response of such assemblies. The mechanical response of such membranes is studied by minimizing the Gibbs free energy which penalizes perturbations of the changes of areal stretch and their gradients only (Deseri and Zurlo, 2013). As material instabilities arise whenever areal stretches characterizing homogeneous configurations lie inside the spinoidal zone of the free energy density, bifurcations from such configurations are shown to occur as oscillatory perturbations of the in-plane displacement. Experimental observations (Espinosa et al., 2011) show a power-law in-plane viscous behavior of lipid structures allowing for an effective viscoelastic behavior of lipid membranes, which falls in the framework of Fractional Hereditariness. A suitable generalization of the variational principle invoked for the elasticity is applied in this case, and the corresponding Euler-Lagrange equation is found together with a set of boundary and initial conditions. Separation of variables allows for showing how Fractional Hereditariness owes bifurcated modes with a larger number of spatial oscillations than the corresponding elastic analog. Indeed, the available range of areal stresses for material instabilities is found to increase with respect to the purely elastic case. Nevertheless, the time evolution of the perturbations solving the Euler-Lagrange equation above exhibits time-decay and the large number of spatial oscillation slowly relaxes, thereby keeping the features of a long-tail type time-response. PMID:26897568

  7. Pediatric hereditary angioedema due to C1-inhibitor deficiency

    Directory of Open Access Journals (Sweden)

    Farkas Henriette

    2010-07-01

    Full Text Available Abstract Hereditary angioedema (HAE resulting from the deficiency of the C1 inhibitor (C1-INH is a rare, life-threatening disorder. It is characterized by attacks of angioedema involving the skin and/or the mucosa of the upper airways, as well as the intestinal mucosa. In approximately 50 per cent of cases, clinical manifestations may appear during childhood. The complex management of HAE in pediatric patients is in many respects different from the management of adults. Establishing the diagnosis early, preferably before the onset of clinical symptoms, is essential in cases with a positive family history. Complement studies usually afford accurate diagnosis, whereas molecular genetics tests may prove helpful in uncertain cases. Appropriate therapy, supported by counselling, suitable modification of lifestyle, and avoidance of triggering factors (which primarily include mechanical trauma, mental stress and airway infections in children may spare the patient unnecessary surgery and may prevent mortality. Prompt control of edematous attacks, short-term prophylaxis and intermittent therapy are recommended as the primary means for the management of pediatric cases. Medicinal products currently used for the treatment of children with hereditary angioedema include antifibrinolytics, attenuated androgens, and C1-INH replacement therapy. Current guidelines favour antifibrinolytics for long-term prophylaxis because of their favorable safety profile but efficacy may be lacking. Attenuated androgens administered in the lowest effective dose are another option. C1-INH replacement therapy is also an effective and safe agent for children. Regular monitoring and follow-up of patients are necessary.

  8. 血液透析与肾移植患者肾性骨病的转归%Comparative study of renal osteodystrophy between maintenance hemodialysis and kidney transplantation

    Institute of Scientific and Technical Information of China (English)

    谢飞; 王汉民; 李振江

    2004-01-01

    BACKGROUND: Tile prevention and treatment of renal osteodystrophy directly affect tile long term survivals of chronic renal failure patients,thereby, there is important significances to comparative study the difference of renal osteodystrophy between maintenance hemodialysis and kidney transplantation.OBJECTIVE: To observe the variances of serous phosphorus (P) and parathyroid hormone (PTH) concentrations in the patients before and after either maintenance hemodialysis (MHD) or kidney transplantation for discussions of the treatment and prognosis of renal osteodystrophy.SETTING, PARTICIPANTS and METHODS: Forty chronic renal failure patients who accorded with the clinical diagnostic criteria and suffered from hyperphosphatemia and high serous PTH level as well were selected fiom the hemodialysis center of Xijing Hospital Affiliated to Fourth Military Medical University of Chinese PLA, in which 20 cases were allocated into MHD group and 20 cases were allocated into kidney transplantation group (transplantation group) . Another 20 healthy subjects were selected into control group. Patients in MHD group were treated with MHD, and patients il transplantation group were treated with kidney allograft transplantation with preferably postoperative recovery.MAIN OUTCOME MEASURES: The comparisons of serous P and PTH before and after treatnents in both case groups.RESULTS: The serous P and PTH after hemodialysis or kidney transplantation were significantly decreased compared with those before hemodialysis or kidney transplantation ( t = 3.15, P < 0.001) . However, the serous PTH levels [(278.20+95.84) ng/L] in patients of MHD group were higher than that of control group [ (21.60 + 16.60) ng/L], moreover, the serous levels of P and PTH returned to higher levels before next MHD.CONCLUSION: Serous levels of P and PTH in patients of MHD group are still higher than that of healthy subjects, while there is no signifieant dffference of serous levels of P and PTH between the

  9. Therapeutic effect of a case classics McCune-Albright syndrome an Heredity d related document analysis%经典McCune-Albright综合征1例疗效及文献分析

    Institute of Scientific and Technical Information of China (English)

    王会贞; 卫海燕(通讯作者); 陈永兴

    2013-01-01

    objective:To promote the awareness of McCune-Albright syndrome (MAS), and explore its treatment. Methods:Based on a MAS patient’s clinical data and treatment effect and by reviewing relative literatures, a detailed analysis was carried out to explore the etiology, clinical manifestations, diagnosis and treatment of MAS. Results:The MAS child showed significant increased skeletal maturity, obvious bone fibrosis progress and change of uterine volume and ovarian cystic dark space before treatment. After tamoxifen therapy, the child’s uterine volume and ovarian cystic dark space narrowed, while between the period of drug withdrawal and next colporrhagia, the uterine volume and ovarian cystic dark areas increased again. After two months’ letrozole treatment, the child’s breast showed B1stage, breast nuclear disappeared, the volume of uterine reduced significantly, and there was no colporrhagia again. Conclusions: There was no radical cure for MAS, the main treatment was symptomatic treatment.Tamoxifen and letrozole were both effective to MAS children with peripheral precocious puberty.%目的:提高对McCune-Albright综合征(McCune-Albright syndrome,MAS)的认识,探讨治疗方案。方法:通过1例MAS患者的临床资料、治疗效果和文献复习,详细分析MAS的病因、临床表现、诊断及治疗。结果:给予他莫西芬治疗前患儿骨骼成熟度明显增加,骨纤维化进展明显,子宫体积、卵巢囊性暗区变化明显;给予他莫西芬治疗2月后患儿子宫体积、卵巢囊性暗区缩小,停药后至此次阴道出血前子宫体积、卵巢囊性暗区明显增大。来曲唑治疗2月后乳房B1期,乳核消失,未出现阴道出血,查腹部彩超示子宫体积明显缩小。结论:MAS的治疗主要是对症治疗,尚无有效根治方法。他莫西芬、来曲唑对伴有外周性性早熟的MAS患儿具有一定疗效,可抑制性早熟进一步发展。

  10. Cerebral metabolism of glucose in benign hereditary chorea

    International Nuclear Information System (INIS)

    Benign hereditary chorea (BHC) is an autosomal dominant disorder characterized by chorea of early onset with little or no progression. There is marked clinical variability in this disease with some subjects having onset in infancy and others with onset in early adulthood. In contrast to Huntington's disease (HD), there is no dementia. Computed tomography is normal in all subjects with no evidence of caudate nucleus atrophy. We present the results of positron emission tomography using 18F-2-fluorodeoxyglucose on three patients with this disorder from two families. Cerebral glucose metabolism in one patient was decreased in the caudate nucleus, as previously reported in HD. The other two persons from a second family showed a relative decrease in metabolic rates of glucose in the caudate when compared with the thalamus. It appears that caudate hypometabolism is not specific for HD. These findings suggest that the caudate nucleus may play a significant role in the pathophysiology of some persons with BHC

  11. Antiretroviral therapy-induced Leber’s hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Anand Moodley

    2014-05-01

    Full Text Available Optic neuropathy in HIV-infected patients results from the HIV infection itself, post-infectious auto-immune disease, opportunistic infections and drugs. Nucleoside reverse transcriptase inhibitors (NRTIs such as zidovudine and stavudine have known mitochondrial toxicity and can cause mitochondrial myopathies, neuropathies, hyperlactataemia, and can induce mitochondrial genetic disorders. Individuals with the mutation for Leber’s hereditary optic neuropathy (LHON, a mitochondrial disorder, are usually asymptomatic but develop visual loss when exposed to external triggers such as smoking. We report on two HIV-infected patients with LHON mutations (m.14484T>C and m.11778G>A who developed profound visual loss with antiretroviral therapy. We postulate that the phenotypic expression of LHON in these genetically predisposed individuals was triggered by NRTI drugs lamivudine and tenofovir when used in combination, despite their relatively weak mitochondrial toxic effects. 

  12. Power-law hereditariness of hierarchical fractal bones.

    Science.gov (United States)

    Deseri, Luca; Di Paola, Mario; Zingales, Massimiliano; Pollaci, Pietro

    2013-12-01

    In this paper, the authors introduce a hierarchic fractal model to describe bone hereditariness. Indeed, experimental data of stress relaxation or creep functions obtained by compressive/tensile tests have been proved to be fit by power law with real exponent 0 ⩽ β ⩽1. The rheological behavior of the material has therefore been obtained, using the Boltzmann-Volterra superposition principle, in terms of real order integrals and derivatives (fractional-order calculus). It is shown that the power laws describing creep/relaxation of bone tissue may be obtained by introducing a fractal description of bone cross-section, and the Hausdorff dimension of the fractal geometry is then related to the exponent of the power law. PMID:23836622

  13. Diagnosis and treatment of hereditary tyrosinemia in Japan.

    Science.gov (United States)

    Nakamura, Kimitoshi; Matsumoto, Shirou; Mitsubuchi, Hiroshi; Endo, Fumio

    2015-01-01

    Hereditary tyrosinemia is an autosomal recessive inherited disease that manifests as three types (types I-III). We conducted a nationwide survey of this disease in Japan, and here review the results in relation to prevalence, clinical characteristics, and treatment and diagnosis. A definitive diagnosis of tyrosinemia type I is difficult to obtain based only on blood tyrosine level. Detection of succinylacetone using dried blood spots or urinary organic acid analysis, however, is useful for diagnosis. In tyrosinemia type I, dietary therapy and nitisinone (Orfandin®) are effective. Prognosis is greatly affected by the complications of liver cancer and hypophosphatemic rickets; even patients that are treated early with nitisinone may develop liver cancer. Long-term survival can be expected in type I if nitisinone therapy is effective. Prognosis in types II and III is relatively good. PMID:25443793

  14. [Hereditary gelsolin amyloidosis--40 years of Meretoja disease].

    Science.gov (United States)

    Kiuru-Enari, Sari; Haltia, Matti

    2010-01-01

    Hereditary gelsolin amyloidosis is an autosomally dominantly inherited systemic disease, first described in 1969 by the Finnish ophthalmologist Jouko Meretoja. The estimated number of disease carriers in Finland is almost 1 000, and the disease has subsequently been found in many other countries as well. It's typical initial manifestation is lattice corneal dystrophy, detected at biomicroscopic examination of the eye by the age of 25 to 30 years, followed by slowly progressing cranial neuropathy with bilateral facial palsy, polyneuropathy and generalized cutis laxa. Meretoja's disease is caused by mutations of the gelsolin gene, leading to the production and aberrant processing of variant gelsolin and deposition of its fragments in various tissues in the form of amyloid fibrils. PMID:20597346

  15. CDH1 germline mutations and hereditary lobular breast cancer.

    Science.gov (United States)

    Corso, Giovanni; Intra, Mattia; Trentin, Chiara; Veronesi, Paolo; Galimberti, Viviana

    2016-04-01

    Hereditary diffuse gastric cancer is an autosomal dominant inherited disease associated of CDH1 germline mutations (that encodes for the E-cadherin protein), and lobular breast cancer is the second most frequent type of neoplasia. Recently, novel E-cadherin constitutional alterations have been identified in pedigree clustering only for lobular breast carcinoma without evidence of diffuse gastric tumors and in absence of BRCA1/2 mutations. This first evidence opens novel questions about the inherited correlation between diffuse gastric and lobular breast cancers. In this brief review we revise the literature data about the CDH1 mutation frequency affecting exclusively lobular breast cancer, providing clinical recommendation for asymptomatic mutation carriers. PMID:26759166

  16. Hereditary hemochromatosis in an Indian origin: A rare case report

    Directory of Open Access Journals (Sweden)

    R L Geetha

    2015-01-01

    Full Text Available Hereditary hemochromatosis (HH is manifested as an iron overload in different organs due to homozygosity of a single autosomal mutation. If untreated it leads to conditions such as liver cirrhosis, type 1 diabetes mellitus, hypogonadotropic hypogonadism, cardiomyopathy, arthritis, and bronze coloring of the skin. Hemochromatosis affects as many as 1 in every 200 people in the United States, but in India the reports of genetic study are rare and virtually unexplored. It is also possible that in India clinical hemochromatosis could be masked by iron deficiency. Patients with HH may be either asymptomatic or symptomatic. When symptomatic, there is a wide range of symptoms and a high index of suspicion based on the symptoms is necessary to diagnose the entity. We report an interesting and rare case of HH in a 35-year-old male of Indian origin, who presented with icterus and fever of acute onset with negative HFE genetic mutations.

  17. Pediatric Hereditary Angioedema: Onset, Diagnostic Delay, and Disease Severity.

    Science.gov (United States)

    Christiansen, Sandra C; Davis, Donna K; Castaldo, Anthony J; Zuraw, Bruce L

    2016-09-01

    Hereditary angioedema (HAE) typically presents in childhood. Large gaps remain in our understanding of the natural history of HAE during childhood. We examined age of onset, delay in diagnosis, androgen exposure, and their influence on ultimate disease severity in a large cohort of patients with HAE. Median age of first swelling was 11 years with a median age at diagnosis of 19 years. Earlier onset of symptoms correlated with longer delays in diagnosis (P < .001) and predicted a more severe disease course, including increased number of attacks per year (P = .0009) and hospital admissions (P = .009). Earlier age of onset also significantly correlated with increased perceived HAE severity (P = .0002), negative overall life impact (P < .0001), and use of anabolic androgen. Our observations highlight the importance of early HAE diagnosis and suggest the necessity of a disease management plan once the diagnosis has been made. PMID:26581355

  18. Optimizing hereditary angioedema management through tailored treatment approaches.

    Science.gov (United States)

    Nasr, Iman H; Manson, Ania L; Al Wahshi, Humaid A; Longhurst, Hilary J

    2016-01-01

    Hereditary angioedema (HAE) is a rare but serious and potentially life threatening autosomal dominant condition caused by low or dysfunctional C1 esterase inhibitor (C1-INH) or uncontrolled contact pathway activation. Symptoms are characterized by spontaneous, recurrent attacks of subcutaneous or submucosal swellings typically involving the face, tongue, larynx, extremities, genitalia or bowel. The prevalence of HAE is estimated to be 1:50,000 without known racial differences. It causes psychological stress as well as significant socioeconomic burden. Early treatment and prevention of attacks are associated with better patient outcome and lower socioeconomic burden. New treatments and a better evidence base for management are emerging which, together with a move from hospital-centered to patient-centered care, will enable individualized, tailored treatment approaches. PMID:26496459

  19. Hereditary Breast Cancer: The Era of New Susceptibility Genes

    Directory of Open Access Journals (Sweden)

    Paraskevi Apostolou

    2013-01-01

    Full Text Available Breast cancer is the most common malignancy among females. 5%–10% of breast cancer cases are hereditary and are caused by pathogenic mutations in the considered reference BRCA1 and BRCA2 genes. As sequencing technologies evolve, more susceptible genes have been discovered and BRCA1 and BRCA2 predisposition seems to be only a part of the story. These new findings include rare germline mutations in other high penetrant genes, the most important of which include TP53 mutations in Li-Fraumeni syndrome, STK11 mutations in Peutz-Jeghers syndrome, and PTEN mutations in Cowden syndrome. Furthermore, more frequent, but less penetrant, mutations have been identified in families with breast cancer clustering, in moderate or low penetrant genes, such as CHEK2, ATM, PALB2, and BRIP1. This paper will summarize all current data on new findings in breast cancer susceptibility genes.

  20. Hamilton cycles in almost distance-hereditary graphs

    OpenAIRE

    Chen Bing; Ning Bo

    2013-01-01

    Let G be a graph on n ≥ 3 vertices. A graph G is almost distance-hereditary if each connected induced subgraph H of G has the property dH(x, y) ≤ dG(x, y) + 1 for any pair of vertices x, y ∈ V(H). Adopting the terminology introduced by Broersma et al. and Čada, a graph G is called 1-heavy if at least one of the end vertices of each induced subgraph of G isomorphic to K1,3 (a claw) has degree at least n/2, and is called claw-heavy if each claw of G has a pair of end vertices with degree sum at...

  1. [Hereditary non-polyposis colorectal cancer. Report of four siblings].

    Science.gov (United States)

    Zárate, Alejandro; Alvarez, Karin; Wielandt, Ana María; Hevia, Montserrat; De la Fuente, Marjorie; Carvallo, Pilar; López-Köstner, Francisco

    2008-06-01

    Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch Syndrome is an autosomic dominant syndrome involving 596-1096 of colorectal cancer patients. Mutations in MLH1 and MSH2 genes account for most cases. These two genes participate in the DNA mismatch repair pathway. Therefore mutation carriers show microsatellite instability (MSI) in tumors. This syndrome is characterized by the early development of colorectal cancer (before 50 years) and an increased incidence of cancer in other organs. We report four siblings from a family diagnosed with HNPCC. All of them were subjected to colonic surgery for colorectal cancer Moreover, one patient developed an ampulloma after her colon surgery. The molecular-genetic analysis revealed three brothers with microsatellite instability in the tumor tissue, the absence of the MLH1 protein, and the presence of a germ line mutation localized in introm 15 of the MLH1 gene. PMID:18769833

  2. Hereditary haemorrhagic telangiectasia: a cause of preventable morbidity and mortality.

    LENUS (Irish Health Repository)

    Brady, A P

    2012-01-31

    Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant condition whose effects are mediated through deficient blood vessel formation and regeneration, with multisystem involvement. Patients are usually aware of resulting skin telangiectasia and epistaxis, but are also exposed to dangers posed by occult vascular malformations in other organs. About 15-35% of HHT patients have pulmonary AVMs (PAVMs), 10% have cerebral AVMs (CAVMs), 25-33% suffer significant GI blood loss from GI tract telangiectasia, and an unknown but high percentage have liver involvement. In total, 10% of affected individuals die prematurely or suffer major disability from HHT, largely because of bleeding from CAVMs and PAVMs, or paradoxical embolization through PAVMs. Screening for and early intervention to treat occult PAVMs and CAVMs can largely eliminate these risks, and should be undertaken in a specialist centre. The National HHT Center in The Mercy University Hospital in Cork is the referral centre for HHT screening in Ireland.

  3. ANAESTHETIC MANAGEMENT OF A CASE OF HEREDITARY SPHEROCYTOSIS FOR SPLENECTOMY AND CHOLECYSTECTOMY.

    Directory of Open Access Journals (Sweden)

    Jyotsna

    2012-11-01

    Full Text Available ABSTRACT: We report successful anaesthetic management of a pat ient with hereditary spherocytosis who underwent laproscopic splenectomy, ch olecystectomy and appendioectomy. Hereditary spherocytosis is a familial hemolytic di sorder with marked heterogeneity of clinical features, ranging from asymptomatic condition to a f ulminant hemolytic anaemia. Commonly recommended perioperative management in these patien ts includes preemptive erythrocyte transfusion, aggressive hydration and avoidance of hypoxia, aplastic crisis, hypothermia and acidosis. The management of such a case is challeng ing from anaesthetic point of view because of sickling oriented anaesthetic approach. Key words: Hereditary spherocytosis, splenectomy, cholecystectomy, perioperative management.

  4. Obstetrics/gynecology residents' knowledge of hereditary breast and ovarian cancer and Lynch syndrome.

    Science.gov (United States)

    Ready, Kaylene J; Daniels, Molly S; Sun, Charlotte C; Peterson, Susan K; Northrup, Hope; Lu, Karen H

    2010-09-01

    Although there have been many studies regarding physicians' knowledge of hereditary cancer syndromes, very little information exists regarding medical residents' knowledge of hereditary cancer syndromes. Obstetrics/gynecology residents completed a test which evaluated their knowledge of hereditary breast and ovarian cancer and Lynch syndrome. Areas of relative deficit were identified. Residents indicated a desire and need for more education regarding this topic. Cancer genetics education programs should place more emphasis on the areas in which residents' appeared to be deficient in order to aid future physicians in the identification of high-risk individuals. PMID:20186516

  5. Renal AA amyloidosis in a patient with hereditary complete complement C4 deficiency

    Directory of Open Access Journals (Sweden)

    Imed Helal

    2011-01-01

    Full Text Available Hereditary complete C4 deficiency has until now been reported in 30 cases only. A disturbed clearance of immune- complexes probably predisposes these individuals to systemic lupus erythematosus, other immune- complex diseases and recurrent microbial infections. We present here a 20- year- old female with hereditary complete C4 deficiency. Renal biopsy demonstrated renal AA amyloidosis. This unique case further substantiates that deficiency of classical pathway components predisposes to the development of recurrent microbial infections and that the patients may develop AA amyloidosis. Furthermore, in clinical practice, the nephrotic syndrome occurring in a patient with hereditary complete complement C4 deficiency should lead to the suspicion of renal AA amyloidosis.

  6. Laparoscopic splenectomy for hereditary spherocytosis-preliminary report.

    Science.gov (United States)

    Rogulski, Robert; Adamowicz-Salach, Anna; Matysiak, Michał; Piotrowski, Dariusz; Gogolewski, Michał; Piotrowska, Anna; Roik, Danuta; Kamiński, Andrzej

    2016-06-01

    Splenectomy is considered standard surgical therapy in hereditary spherocytosis. The procedure is indicated in patients with severe anemia, recurrent hemolytic, and aplastic crises. The aim of the study was to assess treatment outcomes in patients with hereditary spherocytosis who underwent total or partial laparoscopic splenectomy. Fifteen patients aged 4-17 yr underwent laparoscopic splenectomy from 2009 to 2012. Partial and total splenectomies were performed (five and 10 children, respectively). Hematologic parameters, liver function tests, and splenic volume before and after the surgery were analyzed retrospectively. Total follow-up was 1-30 months. Hospitalization and operating time were similar in both groups. In partial splenectomy group, branches of splenic arteries gave better blood supply than short gastric vessels. In both groups, hematologic parameters were improved. Postoperative markedly elevated platelet count was maintained up to 6 months, and after that, platelet count gradually decreased to normal values. Bilirubin level was decreased in early postoperative period; however, it increased later to achieve levels lower than in preoperative period. No severe general infections were observed in both groups. Laboratory parameters (hemoglobin and bilirubin concentrations and RBC) after the surgery improved in all patients, and the effect was maintained during 12 months of follow-up. Platelet count increased significantly after the surgery and was maintained at high levels during the next 6 months. However, it returned to preoperative levels within a year after the surgery. Our study showed that partial splenectomy was not inferior to total splenectomy. However, full assessment requires longer follow-up and larger group of patients. PMID:26268883

  7. Hereditary angioedema: what the gastroenterologist needs to know

    Directory of Open Access Journals (Sweden)

    Ali MA

    2014-11-01

    Full Text Available M Aamir Ali, Marie L Borum Division of Gastroenterology and Liver Diseases, George Washington University, Washington, DC, USA Abstract: Up to 93% of patients with hereditary angioedema (HAE experience recurrent abdominal pain. Many of these patients, who often present to emergency departments, primary care physicians, general surgeons, or gastroenterologists, are misdiagnosed for years and undergo unnecessary testing and surgical procedures. Making the diagnosis of HAE can be challenging because symptoms and attack locations are often inconsistent from one episode to the next. Abdominal attacks are common and can occur without other attack locations. An early, accurate diagnosis is central to managing HAE. Unexplained abdominal pain, particularly when accompanied by swelling of the face and extremities, suggests the diagnosis of HAE. A family history and radiologic imaging demonstrating edematous bowel also support an HAE diagnosis. Once HAE is suspected, C4 and C1 esterase inhibitor (C1-INH laboratory studies are usually diagnostic. Patients with HAE may benefit from recently approved specific treatments, including plasma-derived C1-INH or recombinant C1-INH, a bradykinin B2-receptor antagonist, or a kallikrein inhibitor as first-line therapy and solvent/detergent-treated or fresh frozen plasma as second-line therapy for acute episodes. Short-term or long-term prophylaxis with nanofiltered C1-INH or attenuated androgens will prevent or reduce the frequency and severity of episodes. Gastroenterologists can play a critical role in identifying and treating patients with HAE, and should have a high index of suspicion when encountering patients with recurrent, unexplained bouts of abdominal pain. Given the high rate of abdominal attacks in HAE, it is important for gastroenterologists to appropriately diagnose and promptly recognize and treat HAE, or refer patients with HAE to an allergist. Keywords: hereditary angioedema, abdominal pain, diagnosis

  8. Computational complexity of classical problems for hereditary clique-helly graphs

    Directory of Open Access Journals (Sweden)

    Flavia Bonomo

    2004-12-01

    Full Text Available A graph is clique-Helly when its cliques satisfy the Helly property. A graph is hereditary clique-Helly when every induced subgraph of it is clique-Helly. The decision problems associated to the stability, chromatic, clique and clique-covering numbers are NP-complete for clique-Helly graphs. In this note, we analyze the complexity of these problems for hereditary clique-Helly graphs. Some of them can be deduced easily by known results. We prove that the clique-covering problem remains NP-complete for hereditary clique-Helly graphs. Furthermore, the decision problems associated to the clique-transversal and the clique-independence numbers are analyzed too. We prove that they remain NP-complete for a smaller class: hereditary clique-Helly split graphs.

  9. Hereditary non-polyposis colorectal cancer : Identification of mutation carriers and assessing pathogenicity of mutations

    NARCIS (Netherlands)

    Niessen, RC; Sijmons, RH; Berends, MJW; Ou, J; Hofstra, RNW; Kleibeuker, JH

    2004-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is an autosomal dominantly inherited disorder that is characterized by susceptibility to colorectal cancer and extracolonic malignancies, in particular endometrial cancer. HNPCC is caused by pathogenic mutations

  10. Hereditary Cancer: Example of a Public Health Approach to Ensure Population Health Benefits of Genetic Medicine

    Science.gov (United States)

    Cragun, Deborah; Lewis, Courtney; Camperlengo, Lucia; Pal, Tuya

    2016-01-01

    This article introduces the identification, prevention, and treatment of hereditary cancer as an important public health concern. Hereditary cancer research and educational outreach activities are used to illustrate how public health functions can help to achieve health benefits of genetic and genomic medicine. First, we evaluate genetic service delivery through triangulating patient and provider survey results which reveal variability among providers in hereditary cancer knowledge and genetic service provision. Second, we describe efforts we have made to assure competency among healthcare providers and to inform, educate and empower patients with regard to the rapidly evolving field of genomics and hereditary cancer. Lastly, key policy-issues raised by our experiences are discussed in the context of how they may help us to more effectively translate future genomic technologies into practice in order to attain population health benefits from genetic and genomic medicine.

  11. Open-label, multicenter study of self-administered icatibant for attacks of hereditary angioedema

    DEFF Research Database (Denmark)

    Aberer, W; Maurer, M; Reshef, A; Longhurst, H; Kivity, S; Bygum, Anette; Caballero, T; Bloom, B; Nair, N; Malbrán, A

    2014-01-01

    Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self...

  12. Hereditary haemorrhagic telangiectasia: a population-based study of prevalence and mortality in Danish patients

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Vase, P; Green, A

    1999-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by telangiectatic lesions. The disease manifestations are variable and include epistaxis, gastrointestinal bleeding, pulmonary arteriovenous malformations and cerebral arteriovenous malformations. Early...

  13. Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Møller, T R; Brusgaard, K;

    2005-01-01

    BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease, characterized by a wide variety of clinical manifestations, including epistaxis, gastrointestinal (GI) bleeding, pulmonary arteriovenous malformations (PAVMs) and neurological symptoms. HHT is a genetically...

  14. Genetics 101 — The Hereditary Material of Life | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Genetics 101 Genetics 101 — The Hereditary Material of Life Past Issues / Summer 2013 Table of Contents Genetics is the study of heredity, the process in ...

  15. The peculiarities of HCT signs at hereditary predisposition to chronic rhinosinusitis

    International Nuclear Information System (INIS)

    The peculiarities of CT anatomy of the nasal cavity and the signs of chronic rhinosinusitis in patients with hereditary predisposition and without it was detected. The findings of the investigations of 334 patients with CRS were analyzed in details.

  16. The telescope conjecture for hereditary rings via Ext-orthogonal pairs

    OpenAIRE

    Krause, Henning; Stovicek, Jan

    2008-01-01

    For the module category of a hereditary ring, the Ext-orthogonal pairs of subcategories are studied. For each Ext-orthogonal pair that is generated by a single module, a 5-term exact sequence is constructed. The pairs of finite type are characterized and two consequences for the class of hereditary rings are established: homological epimorphisms and universal localizations coincide, and the telescope conjecture for the derived category holds true. However, we present examples showing that nei...

  17. A new family with hereditary lysozyme amyloidosis with gastritis and inflammatory bowel disease as prevailing symptoms

    OpenAIRE

    Jean, Estelle; Ebbo, Mikael; Valleix, Sophie; Benarous, Lucas; Heyries, Laurent; Grados, Aurélie; Bernit, Emmanuelle; Grateau, Gilles; Papo, Thomas; Granel, Brigitte; Daniel, Laurent; Harlé, Jean-Robert; Schleinitz, Nicolas

    2014-01-01

    Background Systemic amyloidoses is a heterogeneous group of diseases either acquired or hereditary. Amyloidoses can involve the gastrointestinal tract and the nature of the precursor protein that forms the fibrils deposits should be identified to adjust the treatment and evaluate the prognosis. Lysozyme amyloidosis (ALys) is a rare, systemic non neuropathic hereditary amyloidosis with a heterogenous phenotype including gastrointestinal, renal and hepatic symptoms. Case presentation We report ...

  18. MSI-Testing in Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC)

    OpenAIRE

    Annegret Müller; Tina Bocker Edmonston; Wolfgang Dietmaier; Reinhard Büttner; Richard Fishel; Josef Rüschoff

    2004-01-01

    Genomic instability at simple repeated sequences, termed microsatellite instability (MSI), plays an important role in the analysis of sporadic and hereditary colon cancers. In hereditary non-polyposis colorectal cancer syndrome (HNPCC) more than 90% of cases show MSI, whereas only 10–15% of sporadic colorectal cancers do so. Thus, microsatellite analysis is commonly used as the first diagnostic screening test for HNPCC. In 1997, an international collaborative workshop sponsored by the Nationa...

  19. Pulmonary arteriovenous malformations: screening procedures and pulmonary angiography in patients with hereditary hemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Oxhøj, H; Andersen, P E;

    1999-01-01

    Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited disease with a high prevalence of pulmonary arteriovenous malformations (PAVMs). The first symptom of HHT may be stroke or fatal hemoptysis associated with the presence of PAVM.......Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited disease with a high prevalence of pulmonary arteriovenous malformations (PAVMs). The first symptom of HHT may be stroke or fatal hemoptysis associated with the presence of PAVM....

  20. Nasal Sinus Leiomyosarcoma in a Patient with History of Non-Hereditary Unilateral Treated Retinoblastoma

    OpenAIRE

    Fitzpatrick, Sarah G.; Woodworth, Bradford A.; Monteiro, Carmela; Makary, Raafat

    2010-01-01

    Hereditary patients with a history of treated retinoblastoma (RB) have a greatly increased risk of a broad spectrum of secondary malignancies appearing many years later, with a high incidence in the head and neck region. Leiomyosarcomas (LMS) account for up to 58% of these tumors. LMS in the sinonasal region generally are uncommon and are associated with a locally aggressive course and have a poor prognosis. RB may occur in two forms. The hereditary form is generally bilateral but can present...

  1. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Bowen Tom

    2010-07-01

    Full Text Available Abstract Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010. Methods The Canadian Hereditary Angioedema Network (CHAEN/Réseau Canadien d'angioédème héréditaire (RCAH http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review. Results This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. Conclusions Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.

  2. [Prophylactic use of icatibant before tracheal intubation of a patient with hereditary angioedema type III. (A literature review of perioperative management of patients with hereditary angioedema type III)].

    Science.gov (United States)

    Iturri Clavero, F; González Uriarte, A; Tamayo Medel, G; Gamboa Setién, P M

    2014-01-01

    Type III hereditary angioedema is a rare familial disorder that has recently been described as a separate condition. Triggers for episodes of angioedema include surgery, dental procedures, and tracheal intubation maneuvers. Since episodes affecting the upper airway are potentially life-threatening, prophylactic treatment is recommended in these situations. The use of icatibant (Firazyr(®)), for prevention of angioedema prior to tracheal intubation, is reported in a patient with type iii hereditary angioedema. A literature review on the anesthetic management of this condition was conducted. PMID:24931134

  3. Genetic and phenotypic characterization of complex hereditary spastic paraplegia.

    Science.gov (United States)

    Kara, Eleanna; Tucci, Arianna; Manzoni, Claudia; Lynch, David S; Elpidorou, Marilena; Bettencourt, Conceicao; Chelban, Viorica; Manole, Andreea; Hamed, Sherifa A; Haridy, Nourelhoda A; Federoff, Monica; Preza, Elisavet; Hughes, Deborah; Pittman, Alan; Jaunmuktane, Zane; Brandner, Sebastian; Xiromerisiou, Georgia; Wiethoff, Sarah; Schottlaender, Lucia; Proukakis, Christos; Morris, Huw; Warner, Tom; Bhatia, Kailash P; Korlipara, L V Prasad; Singleton, Andrew B; Hardy, John; Wood, Nicholas W; Lewis, Patrick A; Houlden, Henry

    2016-07-01

    The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15, SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease-causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next

  4. Hereditary angioedema: epidemiology, management, and role of icatibant

    Directory of Open Access Journals (Sweden)

    Ghazi A

    2013-05-01

    Full Text Available Aasia Ghazi, J Andrew GrantUniversity of Texas Medical Branch, Division of Allergy and Clinical Immunology, Galveston, TX, USAAbstract: Hereditary angioedema (HAE is an autosomal dominant, potentially life-threatening condition, manifesting as recurrent and self-limiting episodes of facial, laryngeal, genital, or peripheral swelling with abdominal pain secondary to intra-abdominal edema. The estimated prevalence of HAE in the general population is one individual per 50,000, with reported ranges from 1:10,000 to 1:150,000, without major sex or ethnic differences. Various treatment options for acute attacks and prophylaxis of HAE are authorized and available in the market, including plasma-derived (Berinert®, Cinryze®, and Cetor® and recombinant (Rhucin® and Ruconest™ C1 inhibitors, kallikrein inhibitor-ecallantide (Kalbitor®, and bradykinin B2 receptor antagonist-icatibant (Firazyr®. Some of these drugs are used only to treat HAE attacks, whereas others are only approved for prophylactic therapies and all of them have improved disease outcomes due to their different mechanisms of action. Bradykinin and its binding to B2 receptor have been demonstrated to be responsible for most of the symptoms of HAE. Thus icatibant (Firazyr®, a bradykinin B2 receptor antagonist, has proven to be an effective and more targeted treatment option and has been approved for the treatment of acute attacks of HAE. Rapid and stable relief from symptoms of cutaneous, abdominal, or laryngeal HAE attacks has been demonstrated by 30 mg of icatibant in Phase III clinical trials. Self-resolving mild to moderate local site reactions after subcutaneous injection of icatibant were observed. Icatibant is a new, safe, and effective treatment for acute attacks of HAE. HAE has been reported to result in enormous humanistic burden to patients, affecting both physical and mental health, with a negative impact on education, career, and work productivity, and with substantial

  5. Mutations in exons 2 and 3 of the cationic trypsinogen gene in Japanese families with hereditary pancreatitis

    OpenAIRE

    Nishimori, I; Kamakura, M; Fujikawa-Adachi, K; Morita, M.; Onishi, S; Yokoyama, K.; Makino, I; H. Ishida; Yamamoto, M.; Watanabe, S; Ogawa, M

    1999-01-01

    Background/Aims—Single-point mutations in the cationic trypsinogen gene have been reported in hereditary pancreatitis kindreds in the white population. The aim of the present study was to investigate whether similar gene mutations are present in Japanese hereditary pancreatitis kindreds. 
Methods—All five exons of the cationic trypsinogen gene were amplified by polymerase chain reaction and sequenced in six Japanese families with hereditary pancreatitis. 
Results—Two types o...

  6. Hereditary deafness with hydrops and anomalous calcium phosphate deposits

    Energy Technology Data Exchange (ETDEWEB)

    Johnsson, L.G.; Rouse, R.C.; Hawkins, J.E. Jr.; Kingsley, T.C.; Wright, C.G.

    1981-11-01

    The temporal bones from a 58-year-old white woman who had had hereditary congenital deafness were examined with the techniques of microdissection and surface preparations followed by sectioning of the modiolus. There was bilateral, almost total sensorineural degeneration, which also involved the saccule. The degeneration of the distal processes of the cochlear neurons in the osseous spiral lamina was almost complete, whereas numerous ganglion cells and proximal processes remained in the modiolus and the internal auditory canal. Severe cochleo-saccular hydrops was present in the left ear with Reissner's membrane bulging into the horizontal canal. X-ray diffraction and electron probe analysis were used to study the abnormal crystalline deposits in both ears. On the left side the saccular otoconia were composed of calcite, but the utricular macula was covered by a crust of apatite spherulites. More apatite occurred around the maculae and in the scala media. The cupulae were composed of apatite and octacalcium phosphate. On the right side the utricular otoconia were of normal calcite, but there was a deposit of apatite on the macula sacculi. The upper part of the scala media was completely filled by a deposit of apatite and octacalcium phosphate.

  7. Hereditary diffuse gastric cancer: What the clinician should know

    Institute of Scientific and Technical Information of China (English)

    Ryan; Ying; Cong; Tan; Joanne; Ngeow

    2015-01-01

    Hereditary diffuse gastric cancer(HDGC) is an inherited autosomal dominant syndrome with a penetrance of up to 80% affecting diverse geographic populations. While it has been shown to be caused mainly by germline alterations in the E-cadherin gene(CDH1), problematically, the genetic diagnosis remains unknown in up to 60% of patients. Given the important knowledge gaps regarding the syndrome, asymptomatic carriers of CDH1 mutations are advised for a prophylactic total gastrectomy. Intensive annual endoscopic surveillance is the alternative for carriers who decline gastrectomy. As HDGCs have a prolonged indolent phase, this provides a window of opportunity for surveillance and treatment. Recent findings of other gene defects in CTNNA1 and MAP3K6, as well as further characterization of CDH1 mutations and their pathogenicity will change the way HDGC patients are counselled for screening, surveillance and treatment. This review will bring the reader up to date with these changes and discuss future directions for research; namely more accurate risk stratification and surveillance methods to improve clinical care of HDGC patients.

  8. Strumpellin and Spartin, Hereditary Spastic Paraplegia Proteins, are Binding Partners.

    Science.gov (United States)

    Zhao, Jiali; Hedera, Peter

    2015-01-01

    Hereditary spastic paraplegia (HSP) is one of the most heterogeneous neurodegenerative diseases with more than 50 identified genes causing a relatively stereotypical phenotypic presentation. Recent studies of HSP pathogenesis have suggested the existence of shared biochemical pathways that are crucial for axonal maintenance and degeneration. We explored possible interactions of several proteins associated with this condition. Here we report interactions of endogenous and overexpressed strumpellin with another HSP-associated protein, spartin. This biochemical interaction does not appear to be a part of the Wiskott-Aldrich syndrome protein and Scar homologue (WASH) complex because spartin is not co-immunoprecipitated with WASH1 protein. The spartin-strumpellin association does not require the presence of the microtubule interacting and trafficking domain of spartin. Over-expression of mutant forms of strumpellin with the introduced HSP-causing mutations does not alter the colocalization of these two proteins. Knockdown of strumpellin in cultured cortical rat neurons interferes with development of neuronal branching and results in reduced expression of endogenous spartin. Proteosomal inhibition stabilized the levels of spartin and WASH1 proteins, supporting increased spartin degradation in the absence of strumpellin. PMID:25987849

  9. CT findings of hereditary dentatorubral-pallidoluysian atrophy (DRPLA)

    International Nuclear Information System (INIS)

    Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) has recently been recognized as a clinicopathological entity. It may be defined as a multisystem degenerative disease of dominant inheritance, and characterized clinically by a combination of epilepsy, myoclonus, ataxia, dementia, and choreo-athetosis. This paper reports on the CT findings of ten patients (in four families) with DRPLA. In two families, the diagnosis was established on the basis of the clinicopathological findings, while in the other two, the diagnosis was made clinically. Although the CT findings were not identical in all patients, some degree of atrophic change was always observed in the cerebellum, brainstem, and cerebral cortex. Cerebellar atrophy was always accompanied by a dilatation of the fourth ventricle. Midbrain atrophy was characterized by a prominent tegmental atrophy and aqueductal dilatation, such as is seen in progressive supranuclear palsy. Of the four patients over 40 years of age, three had a diffuse hypodensity of the cerebral white matter on CT. To our knowledge, there have been no previous reports on this hypodensity in patients with spino-cerebellar degeneration or Huntington's chorea. CT may be helpful in the differential diagnosis of progressive neuro-degenerative disorders. (author)

  10. CDH1 germline mutation in hereditary gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hai-Dan Wang; Jun Ren; Lian Zhang

    2004-01-01

    This paper provides a bird's-eye view both in preclinical and clinical aspects of E-cadherin germline gene (CDH1)in gastric cancer patients and their families. E-cadherin,a product of CDH1 gene, belonging to the functionally related trans-membrane glycoprotein family, is responsible for the Ca2+-dependent cell-cell adhesion mechanism and contributes to dissociation followed by acquisition of cell motility, which usually occurs in the first step of cancer invasion and metastasis. CDH1 gene germline mutation is common in many types of carcinoma,and occurs very frequent in hereditary gastric carcinoma (HGC) patients and their families. Recently, more and more researches support that E-cadherin plays an important role in the differentiation, growth and invasion of HGC. So it is of great value to clarify its mechanisms both for understanding HGC pathogenesis and for clinical therapy, especially in China, where there are a high risk population of gastric cancer and a high HGC incidence rate. In this paper, recent researches on CDH1 gene mutation, especially its role in tumor genesis and progress of HGC, are reviewed, and advances in evaluation of its mutation status for HGC diagnosis, therapy and prognosis,are also discussed briefly.

  11. The proteomic profile of hereditary inclusion body myopathy.

    Directory of Open Access Journals (Sweden)

    Ilan Sela

    Full Text Available Hereditary inclusion body myopathy (HIBM is an adult onset, slowly progressive distal and proximal myopathy. Although the causing gene, GNE, encodes for a key enzyme in the biosynthesis of sialic acid, its primary function in HIBM remains unknown. The goal of this study was to unravel new clues on the biological pathways leading to HIBM by proteomic comparison. Muscle cultures and biopsies were analyzed by two dimensional gel electrophoresis (2-DE and the same biopsy extracts by isobaric tag for relative and absolute quantitation (iTRAQ. Proteins that were differentially expressed in all HIBM specimens versus all controls in each analysis were identified by mass spectrometry. The muscle cultures 2-DE analysis yielded 41 such proteins, while the biopsies 2-DE analysis showed 26 differentially expressed proteins. Out of the 400 proteins identified in biopsies by iTRAQ, 41 showed altered expression. In spite of the different nature of specimens (muscle primary cultures versus muscle biopsies and of the different methods applied (2D gels versus iTRAQ the differentially expressed proteins identified in each of the three analyses where related mainly to the same pathways, ubiquitination, stress response and mitochondrial processes, but the most robust cluster (30% was assigned to cytoskeleton and sarcomere organization. Taken together, these findings indicate a possible novel function of GNE in the muscle filamentous apparatus that could be involved in the pathogenesis of HIBM.

  12. Unusual presentation of hereditary neuropathy with liability to pressure palsies

    Directory of Open Access Journals (Sweden)

    Andary Michael T

    2008-01-01

    Full Text Available Abstract Background Hereditary neuropathy with liability to pressure palsies (HNPP is an autosomal-dominant painless peripheral neuropathy characterized by episodes of repeated focal pressure neuropathies at sites of entrapment/compression, with a considerable variability in the clinical course. Electrodiagnostic and genetic testing are important in the diagnostic evaluation of these patients. Case presentation We report an unusual HNPP phenotype, five compression neuropathies in four nerves in a patient with bilateral hand numbness. A 42-year-old female, presented with acute bilateral paresthesias and weakness in her hands after starting yoga exercises requiring hyperextension of her hands at the wrists. Her presentation was complicated by: a a remote history of acute onset foot drop and subsequent improvement, b previous diagnoses of demyelinating peripheral neuropathy, possibly Charcot-Marie-Tooth disease, and c exposure to leprosy. Electrodiagnostic testing showed 5 separate compression neuropathies in 4 nerves including: severe left and right ulnar neuropathies at the wrist, left and right median neuropathies at the wrist and left ulnar neuropathy at the elbow. There was a mild generalized, primarily demyelinating, peripheral polyneuropathy. Based on the clinical suspicion and electrodiagnostic findings, consistent with profound demyelination in areas of compression, genetic analysis was done which identified a deletion of the PMP-22 gene consistent with HNPP. Conclusion HNPP can present with unusual phenotypes, such as 5 separate mononeuropathies, bilateral ulnar and median neuropathies at the wrists and ulnar neuropathy at the elbow with mild peripheral demyelinating polyneuropathy associated with the PMP-22 gene deletion.

  13. Management of upper airway edema caused by hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Farkas Henriette

    2010-07-01

    Full Text Available Abstract Hereditary angioedema is a rare disorder with a genetic background involving mutations in the genes encoding C1-INH and of factor XII. Its etiology is unknown in a proportion of cases. Recurrent edema formation may involve the subcutis and the submucosa - the latter can produce obstruction in the upper airways and thereby lead to life-threatening asphyxia. This is the reason for the high, 30-to 50-per-cent mortality of undiagnosed or improperly managed cases. Airway obstruction can be prevented through early diagnosis, meaningful patient information, timely recognition of initial symptoms, state-of-the-art emergency therapy, and close monitoring of the patient. Prophylaxis can substantially mitigate the risk of upper airway edema and also improve the patients' quality of life. Notwithstanding the foregoing, any form of upper airway edema should be regarded as a potentially life-threatening condition. None of the currently available prophylactic modalities is capable of preventing UAE with absolute certainty.

  14. Leber′s hereditary optic neuropathy: The mitochondrial connection revisited

    Directory of Open Access Journals (Sweden)

    Khaled K Abu-Amero

    2011-01-01

    Full Text Available Our current understanding of Leber′s hereditary optic neuropathy (LHON-mitochondrial connection falls short of comprehensive. Twenty years of intensive investigation have yielded a wealth of information about mitochondria, the mitochondrial genome, the metabolism of the optic nerve and other structures, and the phenotypic variability of classic LHON. However, we still cannot completely explain how primary LHON mutations injure the optic nerve or why the optic nerve is particularly at risk. We cannot explain the incomplete penetrance or the male predominance of LHON, the typical onset in young adult life without warning, or the synchronicity of visual loss. Moreover, primary LHON mutations clearly are not present in every family with the LHON phenotype (including multigenerational maternal inheritance, and they are present in only a minority of individuals who have the LHON optic neuropathy phenotype without a family history. All lines of evidence point to abnormalities of the mitochondria as the direct or indirect cause of LHON. Therefore, the mitochondria-LHON connection needs to be revisited and examined closely. This review will attempt to do that and provide an update on various aspects of LHON.

  15. Hereditary breast and gynecological tumors: Italian legal issues.

    Science.gov (United States)

    DI Vella, Giancarlo

    2016-10-01

    The availability of diagnostic and therapeutic procedures that lower the risk for developing hereditary family-related tumors is weighed against Italian ethical and legal provisions. The healthcare environment in which a professional works should require that he possess specific technical, relational and medical competencies based upon legal orientation in addition to scientific evidence. Particular emphasis is attributed to the doctor-patient relationship, with explicit reference to the following: 1) all of the information at hand that is required to achieve a "therapeutic alliance" that combines the best interests of the patient with treatment options; 2) the completeness and intelligibility of health records, as they are likely to explain the background logic and the following of scientific clinical procedure; 3) the observance of guidelines and protocols, and their relevance to the legal responsibility of the individual and health care companies; 4) the need of a multidisciplinary approach in the treatment of these patients and the obligation of the team to have malpractice insurance. Advances on "provisions concerning liability of health personnel", which is currently awaiting approval, allows the professional to protect the patient's health without the fear of being unnecessarily censured, and unjustified from a penal or civil point of view which can deteriorate the relationship of trust and cooperation established. PMID:26924172

  16. Hereditary deafness with hydrops and anomalous calcium phosphate deposits

    International Nuclear Information System (INIS)

    The temporal bones from a 58-year-old white woman who had had hereditary congenital deafness were examined with the techniques of microdissection and surface preparations followed by sectioning of the modiolus. There was bilateral, almost total sensorineural degeneration, which also involved the saccule. The degeneration of the distal processes of the cochlear neurons in the osseous spiral lamina was almost complete, whereas numerous ganglion cells and proximal processes remained in the modiolus and the internal auditory canal. Severe cochleo-saccular hydrops was present in the left ear with Reissner's membrane bulging into the horizontal canal. X-ray diffraction and electron probe analysis were used to study the abnormal crystalline deposits in both ears. On the left side the saccular otoconia were composed of calcite, but the utricular macula was covered by a crust of apatite spherulites. More apatite occurred around the maculae and in the scala media. The cupulae were composed of apatite and octacalcium phosphate. On the right side the utricular otoconia were of normal calcite, but there was a deposit of apatite on the macula sacculi. The upper part of the scala media was completely filled by a deposit of apatite and octacalcium phosphate

  17. Impairment of autophagy: From hereditary disorder to drug intoxication

    International Nuclear Information System (INIS)

    At first, the molecular mechanism of autophagy was unveiled in a unicellular organism Saccharomyces cerevisiae (budding yeast), followed by the discovery that the basic mechanism of autophagy is conserved in multicellular organisms including mammals. Although autophagy was considered to be a non-selective bulk protein degradation system to recycle amino acids during periods of nutrient starvation, it is also believed to be an essential mechanism for the selective elimination of proteins/organelles that are damaged under pathological conditions. Research advances made using autophagy-deficient animals have revealed that impairments of autophagy often underlie the pathogenesis of hereditary disorders such as Danon, Parkinson's, Alzheimer's, and Huntington's diseases, and amyotrophic lateral sclerosis. On the other hand, there are many reports that drugs and toxicants, including arsenic, cadmium, paraquat, methamphetamine, and ethanol, induce autophagy during the development of their toxicity on many organs including heart, brain, lung, kidney, and liver. Although the question as to whether autophagic machinery is involved in the execution of cell death or not remains controversial, the current view of the role of autophagy during cell/tissue injury is that it is an important, often essential, cytoprotective reaction; disturbances in cytoprotective autophagy aggravate cell/tissue injuries. The purpose of this review is to provide (1) a gross summarization of autophagy processes, which are becoming more important in the field of toxicology, and (2) examples of important studies reporting the involvement of perturbations in autophagy in cell/tissue injuries caused by acute as well as chronic intoxication

  18. Deception in simplicity: hereditary phospholamban mutations in dilated cardiomyopathy.

    Science.gov (United States)

    Young, Howard S; Ceholski, Delaine K; Trieber, Catharine A

    2015-02-01

    The sarcoplasmic reticulum (SR) calcium pump (SERCA) and its regulator phospholamban are required for cardiovascular function. Phospholamban alters the apparent calcium affinity of SERCA in a process that is modulated by phosphorylation via the β-adrenergic pathway. This regulatory axis allows for the dynamic control of SR calcium stores and cardiac contractility. Herein we focus on hereditary mutants of phospholamban that are associated with heart failure, such as Arg(9)-Cys, Arg(9)-Leu, Arg(9)-His, and Arg(14)-deletion. Each mutant has a distinct effect on PLN function and SR calcium homeostasis. Arg(9)-Cys and Arg(9)-Leu do not inhibit SERCA, Arg(14)-deletion is a partial inhibitor, and Arg(9)-His is comparable to wild-type. While the mutants have distinct functional effects on SERCA, they have in common that they cannot be phosphorylated by protein kinase A (PKA). Arg(9) and Arg(14) are required for PKA recognition and phosphorylation of PLN. Thus, mutations at these positions eliminate β-adrenergic control and dynamic cardiac contractility. Hydrophobic mutations of Arg(9) cause more complex changes in function, including loss of PLN function and dominant negative interaction with SERCA in heterozygous individuals. In addition, aberrant interaction with PKA may prevent phosphorylation of wild-type PLN and sequester PKA from other local subcellular targets. Herein we consider what is known about each mutant and how the synergistic changes in SR calcium homeostasis lead to impaired cardiac contractility and dilated cardiomyopathy. PMID:25563649

  19. Hereditary angioedema: New therapeutic options for a potentially deadly disorder

    Directory of Open Access Journals (Sweden)

    Eidelman Frank J

    2010-05-01

    Full Text Available Abstract Although the biochemistry of hereditary angioedema (HAE is fairly well understood today, the lag in diagnosis of a decade or more suggests that clinicians have low awareness of this disease. This lag in diagnosis and hence treatment certainly stems from the rarity and complexity of the presentation which can be easily mistaken for allergic and non-allergic reactions alike. The symptoms of the disease include acute swelling of any or multiple parts of the body. The attacks may be frequent or rare, and they may vary substantially in severity, causing stomach discomfort or periorbital swelling in mild cases and hypovolemic shock due to abdominal fluid shift or asphyxiation in the most severe cases. Given that these patients are at significant risk for poor quality of life and death, greater awareness of this disease is needed to ensure that newly available, effective medications are used in these patients. These new medications represent significant advances in HAE therapy because they are targeted at the plasma cascades implicated in the pathophysiology of this disease. The clinical presentation of HAE, overlapping symptoms with other angioedemas, and available therapies are reviewed.

  20. Hereditary Angioedema: Three Cases Report, Members of the Same Family

    Directory of Open Access Journals (Sweden)

    Alexandros Kolokotronis

    2010-01-01

    Full Text Available Background: This current clinical case report highlights three cases of Hereditary angioedema (HAE patients who are all members of the same family (father and his two daughters. The father has C1–INH deficiency, while his daughters have low C1–INH levels: the first possesses only 10% function and the second has low C1–INH level with 0% function. Of note, the second daughter was discovered to have HAE at the age of 2, thus making her the youngest known HAE case report in the English literature.Methods: Assess the efficacy of administration of C1-INH before dental operation as regards the prevention of HAE episode, when total or partial C1-INH deficiency exists.Results: Acute angioedema leading to laryngeal oedema is a possibly fatal complication for HAE patients undergoing dental procedures. Use of both short-term and long-term HAE prophylaxis prior to dental operations might be life saving for those patients.Conclusions: Prevention and early recognition of potential laryngeal oedema that can occur as a complication of dental procedures may be lifesaving for HAE patients.

  1. Growth factors and IL-17 in hereditary angioedema.

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    Salemi, M; Mandalà, V; Muggeo, V; Misiano, G; Milano, S; Colonna-Romano, G; Arcoleo, F; Cillari, E

    2016-05-01

    Hereditary angioedema (HAE) is a rare autosomal dominant disorder, due to C1-inhibitor deficiency, which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways which are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis in basal and crisis state and n = 19 healthy subjects. The samples were tested for IL-17, FGFb, G-CSF and GM-CSF, using Bio-plex kit. Data analysis was performed via nonparametric Spearman's correlations and two sets of linear mixed models. When comparing HAE subjects during basal and crisis states, we found out significantly (i.e., p value <0.05) higher values in crisis states rather than in basal states for the three growth factors and cytokine IL-17. When comparing healthy subjects versus HAE patients at basal state, we found out significantly higher values in HAE subjects only for GM-CSF, FGFb and IL-17, but not for G-CSF. In HAE patients, there is a connection between IL-17 and growth factors. The low-grade inflammation in absence of attacks is demonstrated by constant higher amount of IL-17, FGFb and GM-CSF with respect to healthy patients. This could indicate that in this disease there is a level of activation that maintains the system in a "tick-over state," that can be activate by several stimuli that are able to induce a increase in inflammatory mediators during the acute attack. PMID:25773165

  2. Prophylaxis in hereditary angioedema (HAE) with C1 inhibitor deficiency.

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    Greve, Jens; Strassen, Ulrich; Gorczyza, Marina; Dominas, Nina; Frahm, Uta-Marie; Mühlberg, Heike; Wiednig, Michaela; Zampeli, Vasiliki; Magerl, Markus

    2016-03-01

    Hereditary angioedema (HAE) is a rare congenital disorder characterized by recurrent episodes of subcutaneous or submucosal edema. Laryngeal manifestations can be life-threatening. In the majority of cases, the disease can be adequately treated with an on-demand approach - in some cases, however, short- or long-term prophylaxis is indicated. Attenuated androgens used to be the drugs of choice, but they are associated with considerable side effects and no longer commercially available in the German-speaking countries of the EU. They are currently being replaced by more effective and more tolerable agents such C1-inhibitors, the kallikrein inhibitor ecallantide, and the B2 receptor antagonist icatibant, which have recently obtained market authorization. These new drugs have had a major impact, especially on the indications and procedures for long-term prophylaxis. According to the most recent international consensus papers and our own experience, self-administered C1-inhibitors are now the first option for long-term prophylactic therapy. The decision for prophylaxis should no longer be based on single parameters such as the frequency of attacks but on adequate overall disease control including quality of life. More drugs are currently being developed, which may lead to further changes in the treatment algorithms of HAE. PMID:26972189

  3. Hereditary Angioedema in Swedish Adults: Report From the National Cohort.

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    Nordenfelt, Patrik; Nilsson, Mats; Björkander, Janne; Mallbris, Lotus; Lindfors, Anders; Wahlgren, Carl-Fredrik

    2016-04-12

    Hereditary angioedema (HAE) is rare, disabling and sometimes life-threatening. The aim of this study is to describe its prevalence, symptomatology and treatment in Sweden. A total of 146 patients were identified; 110 adults and 36 children with HAE type I (n = 136) or II (n = 10), giving a minimal HAE prevalence of 1.54/100,000. All patients received a written questionnaire followed by a structured telephone interview. This report focuses on the 102 adults who responded. Females reported 19 attacks in the previous year vs. 9 for males (p < 0.01), and females reported 10 days of sick leave vs. 4 days for males (p < 0.05). For all treated acute attacks, plasma-derived C1-inhibitor concentrate (pdC1INH) (used in 27% of patients) had a good effect. For maintenance treatment, 43% used attenuated androgens and 8% used pdC1INH, which reduced their attack rate by more than 50%. In conclusion, the minimal HAE prevalence in Sweden was 1.54/100,000. HAE affected females more severely. Attenuated androgens and pdC1INH had a good effect on preventing attacks. PMID:26540175

  4. Hereditary Angioedema Attacks: Local Swelling at Multiple Sites.

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    Hofman, Zonne L M; Relan, Anurag; Hack, C Erik

    2016-02-01

    Hereditary angioedema (HAE) patients experience recurrent local swelling in various parts of the body including painful swelling of the intestine and life-threatening laryngeal oedema. Most HAE literature is about attacks located in one anatomical site, though it is mentioned that HAE attacks may also involve multiple anatomical sites simultaneously. A detailed description of such multi-location attacks is currently lacking. This study investigated the occurrence, severity and clinical course of HAE attacks with multiple anatomical locations. HAE patients included in a clinical database of recombinant human C1-inhibitor (rhC1INH) studies were evaluated. Visual analog scale scores filled out by the patients for various symptoms at various locations and investigator symptoms scores during the attack were analysed. Data of 219 eligible attacks in 119 patients was analysed. Thirty-three patients (28%) had symptoms at multiple locations in anatomically unrelated regions at the same time during their first attack. Up to five simultaneously affected locations were reported. The observation that severe HAE attacks often affect multiple sites in the body suggests that HAE symptoms result from a systemic rather than from a local process as is currently believed. PMID:25527240

  5. Hereditary angioedema with normal C1-INH (HAE type III).

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    Riedl, Marc A

    2013-01-01

    Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH), also known as HAE type III, is a familial condition only clinically recognized within the past three decades. Similar to HAE from C1-INH deficiency (HAE types I and II), affected individuals experience unpredictable angioedema episodes of the skin, gastrointestinal tract, and airway. Unique clinical features of HAE with normal C1-INH include the predominance of affected women, frequent exacerbation by estrogen, and a prominence of angioedema that involves the face and oropharynx. The underlying pathophysiology of HAE with normal C1-INH is poorly understood, but indirect evidence points to contact pathway dysregulation with bradykinin-mediated angioedema. Currently, evaluation is complicated by a lack of confirmatory laboratory testing such that clinical criteria must often be used to make the diagnosis of HAE with normal C1-INH. Factor XII mutations have been identified in only a minority of persons affected by HAE with normal C1-INH, limiting the utility of such analysis. To date, no controlled clinical studies have examined the efficacy of therapeutic agents for HAE with normal C1-INH, although published evidence supports frequent clinical benefit with medications shown effective in HAE due to C1-INH deficiency. PMID:24565612

  6. CT findings of hereditary dentatorubral-pallidoluysian atrophy (DRPLA)

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    Tokiguchi, Susumu; Kurashima, Akihiko; Tsuchiya, Toshiaki; Ito, Jusuke; Naito, Haruhiko; Nagai, Hiroko; Wakabayashi, Masatoshi; Morita, Masahiro

    1987-12-01

    Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) has recently been recognized as a clinicopathological entity. It may be defined as a multisystem degenerative disease of dominant inheritance, and characterized clinically by a combination of epilepsy, myoclonus, ataxia, dementia, and choreo-athetosis. This paper reports on the CT findings of ten patients (in four families) with DRPLA. In two families, the diagnosis was established on the basis of the clinicopathological findings, while in the other two, the diagnosis was made clinically. Although the CT findings were not identical in all patients, some degree of atrophic change was always observed in the cerebellum, brainstem, and cerebral cortex. Cerebellar atrophy was always accompanied by a dilatation of the fourth ventricle. Midbrain atrophy was characterized by a prominent tegmental atrophy and aqueductal dilatation, such as is seen in progressive supranuclear palsy. Of the four patients over 40 years of age, three had a diffuse hypodensity of the cerebral white matter on CT. To our knowledge, there have been no previous reports on this hypodensity in patients with spino-cerebellar degeneration or Huntington's chorea. CT may be helpful in the differential diagnosis of progressive neuro-degenerative disorders.

  7. Identification of novel hereditary cancer genes by whole exome sequencing.

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    Sokolenko, Anna P; Suspitsin, Evgeny N; Kuligina, Ekatherina Sh; Bizin, Ilya V; Frishman, Dmitrij; Imyanitov, Evgeny N

    2015-12-28

    Whole exome sequencing (WES) provides a powerful tool for medical genetic research. Several dozens of WES studies involving patients with hereditary cancer syndromes have already been reported. WES led to breakthrough in understanding of the genetic basis of some exceptionally rare syndromes; for example, identification of germ-line SMARCA4 mutations in patients with ovarian hypercalcemic small cell carcinomas indeed explains a noticeable share of familial aggregation of this disease. However, studies on common cancer types turned out to be more difficult. In particular, there is almost a dozen of reports describing WES analysis of breast cancer patients, but none of them yet succeeded to reveal a gene responsible for the significant share of missing heritability. Virtually all components of WES studies require substantial improvement, e.g. technical performance of WES, interpretation of WES results, mode of patient selection, etc. Most of contemporary investigations focus on genes with autosomal dominant mechanism of inheritance; however, recessive and oligogenic models of transmission of cancer susceptibility also need to be considered. It is expected that the list of medically relevant tumor-predisposing genes will be rapidly expanding in the next few years. PMID:26427841

  8. Research on Potential Biomarkers in Hereditary Haemorrhagic Telangiectasia

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    Luisa Maria Botella

    2015-03-01

    Full Text Available Hereditary Hemorrhagic Telangiectasia (HHT is a genetically heterogeneous disorder, involving mutations in two predominant genes known as Endoglin (ENG; HHT1 and Activin receptor like kinase 1 (ACVRL1/ALK1; HHT2, as well as in some less frequent genes, such as MADH4/SMAD4 (JP-HHT or BMP9/GDF2 (HHT5. The diagnosis of HHT patients currently remains at the clinical level, according to the Curaçao criteria, whereas the molecular diagnosis is used to confirm or rule out suspected HHT cases, especially when a well characterized index case is present in the family or in an isolated population. Unfortunately, many suspected patients do not present a clear HHT diagnosis or do not show pathogenic mutations in HHT genes, prompting the need to investigate additional biomarkers of the disease. Here, several HHT biomarkers and novel methodological approaches developed during the last years will be reviewed. On one hand, products detected in plasma or serum samples: soluble proteins (VEGF, TGF-β1, soluble endoglin, angiopoietin-2 and microRNA variants (miR-27a, miR-205, miR-210. On the other hand, differential HHT gene expression fingerprinting, Next Generation Sequencing (NGS of a panel of genes involved in HHT, and infrared spectroscopy combined with Artificial Neural Network (ANN patterns will also be reviewed. All these biomarkers might help to improve and refine HHT diagnosis by distinguishing from the non-HHT population.

  9. Macrosomia, obesity, and macrocephaly as first clinical presentation of PHP1b caused by STX16 deletion.

    Science.gov (United States)

    de Lange, Iris M; Verrijn Stuart, Annemarie A; van der Luijt, Rob B; Ploos van Amstel, Hans Kristian; van Haelst, Mieke M

    2016-09-01

    Pseudohypoparathyroidism (PHP) is a genetic disorder with resistance to parathyroid hormone (PTH) as most important feature. Main subtypes of the disease are pseudohypoparathyroidism 1b (PHP1b) and pseudohypoparathyroidism 1a (PHP1a). PHP1b is characterized by PTH resistance of the renal cortex due to reduced activity of the stimulatory G protein α subunit (Gsα) of the PTH receptor. In addition to resistance to PTH, PHP1a patients also lack sensitivity for other hormones that signal their actions through G protein-coupled receptors and display physical features of Albright hereditary osteodystrophy (AHO), which is not classically seen in PHP1b patients. PHP1a is caused by heterozygous loss-of-function mutations in maternally inherited GNAS exons 1-13, which encode Gsα. PHP1b is often caused by deletion of the STX16 gene, which is thought to have an important role in controlling the methylation and thus imprinting at part of the GNAS locus. Here we present a patient with PHP1b caused by the previously described recurrent 3-kb STX16 deletion. The patient's first symptoms were macrosomia, early onset obesity, and macrocephaly. Since this is an atypical but previously described rare presentation of PHP1b, we reemphasize STX16 deletions and PHP1b as a rare cause for early onset obesity and macrosomia. © 2016 Wiley Periodicals, Inc. PMID:27338644

  10. Single Gene and Syndromic Causes of Obesity: Illustrative Examples.

    Science.gov (United States)

    Butler, Merlin G

    2016-01-01

    Obesity is a significant health problem in westernized societies, particularly in the United States where it has reached epidemic proportions in both adults and children. The prevalence of childhood obesity has doubled in the past 30 years. The causation is complex with multiple sources, including an obesity promoting environment with plentiful highly dense food sources and overall decreased physical activity noted for much of the general population, but genetic factors clearly play a role. Advances in genetic technology using candidate gene approaches, genome-wide association studies, structural and expression microarrays, and next generation sequencing have led to the discovery of hundreds of genes recognized as contributing to obesity. Polygenic and monogenic causes of obesity are now recognized including dozens of examples of syndromic obesity with Prader-Willi syndrome, as a classical example and recognized as the most common known cause of life-threatening obesity. Genetic factors playing a role in the causation of obesity will be discussed along with the growing evidence of single genes and the continuum between monogenic and polygenic obesity. The clinical and genetic aspects of four classical but rare obesity-related syndromes (ie, Prader-Willi, Alström, fragile X, and Albright hereditary osteodystrophy) will be described and illustrated in this review of single gene and syndromic causes of obesity. PMID:27288824

  11. Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene.

    Science.gov (United States)

    Mantovani, Giovanna; Maghnie, Mohamad; Weber, Giovanna; De Menis, Ernesto; Brunelli, Valeria; Cappa, Marco; Loli, Paola; Beck-Peccoz, Paolo; Spada, Anna

    2003-09-01

    Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteodystrophy. Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action [pseudohypoparathyroidism type Ia (PHP Ia)], recent studies provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad, and pituitary. The aim of this study was to investigate the presence of pituitary resistance to hypothalamic hormones acting via Gs alpha-coupled receptors in patients with PHP Ia. Six of nine patients showed an impaired GH responsiveness to GHRH plus arginine, consistent with a complete GH deficiency (GH peak from 2.6-8.6 microg/liter, normal > 16.5), and partial (GH peak 13.9 and 13.6 microg/liter) and normal responses were found in two and one patient, respectively. Accordingly, IGF-I levels were below and in the low-normal range in seven and two patients. All patients had a normal cortisol response to 1 microg ACTH test, suggesting a normal corticotroph function that was confirmed by a normal ACTH and cortisol response to CRH test in three patients. In conclusion, we report that in addition to PTH and TSH resistance, patients with PHP Ia display variable degrees of GHRH resistance, consistent with Gs alpha imprinting in human pituitary. PMID:12970263

  12. Abnormal Methylation Status of the GNAS Exon 1A Region in Pseudohypohyperparathyroidism Combined With Turner Syndrome.

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    Zhu, Jie; Wang, Dong; Ren, An; Xing, Yan; Zhang, Dongliang; Wei, Jun; Yu, Ning; Xing, Xuenong; Ye, Shandong

    2015-12-01

    Pseudohypohyperparathyroidism (PHHP) is a rare type of pseudohypoparathyroidism (PHP), which seems to have a normal skeletal response to parathyroid hormone but shows renal resistance. Almost all patients with PHHP have PHP Ib, a subtype of PHP that is usually caused by GNAS methylation defects, often in exon 1A. Some features of Albright hereditary osteodystrophy can occasionally be found in patients with PHHP, but these features are also common in Turner syndrome. The authors report on an extremely rare case of a patient with PHHP and Turner syndrome, a 47-year-old woman who sought medical attention for hypocalcemia and elevated parathyroid hormone. She had no family history of hypocalcemia and no STX16 gene deletions. She had a mosaic karyotype of 46, X, del(X)(p11.4)/45, XO. Pyrosequencing was performed to determine the GNAS exon 1A methylation. The degree of methylation found in exon 1A of the patient was lower than her unaffected relatives. PMID:26488942

  13. Pes cavus and hereditary neuropathies: when a relationship should be suspected.

    Science.gov (United States)

    Piazza, S; Ricci, G; Caldarazzo Ienco, E; Carlesi, C; Volpi, L; Siciliano, G; Mancuso, M

    2010-12-01

    The hereditary peripheral neuropathies are a clinically and genetically heterogeneous group of diseases of the peripheral nervous system. Foot deformities, including the common pes cavus, but also hammer toes and twisting of the ankle, are frequently present in patients with hereditary peripheral neuropathy, and often represent one of the first signs of the disease. Pes cavus in hereditary peripheral neuropathies is caused by imbalance between the intrinsic muscles of the foot and the muscles of the leg. Accurate clinical evaluation in patients with pes cavus is necessary to exclude or confirm the presence of peripheral neuropathy. Hereditary peripheral neuropathies should be suspected in those cases with bilateral foot deformities, in the presence of family history for pes cavus and/or gait impairment, and in the presence of neurological symptoms or signs, such as distal muscle hypotrophy of limbs. Herein, we review the hereditary peripheral neuropathies in which pes cavus plays a key role as a "spy sign," discussing the clinical and molecular features of these disorders to highlight the importance of pes cavus as a helpful clinical sign in these rare diseases. PMID:20963465

  14. A Family with Hereditary Angioedema Having Been Followed as Familial Mediterranean Fever

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    Gülben Sarıcı

    2009-03-01

    Full Text Available Hereditary angioedema is a rare autosomal dominant disorder resulting from the congenital deficiency of functional C1 esterase inhibitor protein. Patients with hereditary angioedema are clinically characterized by recurrent episodes of swelling of the extremities, face, trunk, airways and abdominal viscera. Attacks may occur either spontaneously or following stress or trauma. The disease is usually associated with attacks of abdominal pain. So, patients may apply for this complaint to other clinics rather than dermatology, and may be misdiagnosed and followed for a long time. Therefore hereditary angioedema should be thought in differential diagnosis of patients suffering from abdominal pain. Here in this writing, we describe a family with hereditary angioedema who has been followed as Familial Mediterranean Fever for a long time. The family members complained from swellings which have been occuring in various regions of the body and disappearing spontaneously, and complained from severe abdominal pain, since childhood. These patients have been followed and tried to be treated with the misdiagnosis of Familial Mediterranean Fever for many years. These patients were diagnosed as hereditary angioedema in our clinic, and benefited from danazol treatment

  15. Whole Exome Sequencing Identifies Multiple, Complex Etiologies in an Idiopathic Hereditary Pancreatitis Kindred

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    Jessica LaRusch

    2012-05-01

    Full Text Available Context Hereditary pancreatitis is the early onset form of chronic pancreatitis that is carried in an autosomal dominant pattern with variable penetrance. While 80% of hereditary pancreatitis has been shown to be due to a single mutation in the trypsinogen gene PRSS1, a number of hereditary pancreatitis families have no identified genetic cause for illness; thus no reliable screening options or clear therapy. Objective To explore the use of massive parallel DNA sequencing technology to discover the etiology of pancreatitis in a family with idiopathic hereditary pancreatitis. Design Candidate gene screening and verification within a kindred. Setting Prospective cohort study, university based. Patients or participants Kindred with idiopathic hereditary pancreatitis. Interventions None. Main outcome measures Identification of DNA variants predicted to increase susceptibility to pancreatitis. Methods Whole exome sequencing of two distantly related subjects with variant-specific confirmation in the subjects and other family members. Results We identified three deleterious genetic changes in the three major pancreatitis associated genes (PRSS1 CNV, SPINK1 c.27delC and CFTR R117H, two of which were carried by each patient. Individual targeted assays confirmed these variations in the two whole exome sequencing patients as well as affected and non-affected pedigree members. Conclusion Whole exome sequencing was useful for rapid screening of candidate genes linked to pancreatitis. This method opens the door for time- and cost-effective screening of multiple disease-associated genes and modifying factors that associate in different ways to generate a complex geneticdisorder.

  16. Clinical management of hereditary angio-oedema in children.

    Science.gov (United States)

    Farkas, Henriette; Harmat, George; Füst, George; Varga, Lilian; Visy, Beáta

    2002-06-01

    Hereditary angio-oedema (HAE) results from the deficiency of C1-esterase inhibitor (C1-INH). The clinical picture of this autosomal dominant disorder is characterized by recurrent attacks of subcutaneous oedema and/or potentially life-threatening swelling of the submucosa. This review discusses the authors' decade-long experience obtained in the treatment and follow-up of pediatric patients with HAE. Twenty-six children with HAE were reviewed. Pedigree analysis was performed in all cases to identify afflicted relatives. C1-INH concentrate was reserved for the emergency treatment of acute oedematous attacks, whereas tranexamic acid and danazol were administered for short- or long-term prophylaxis. Follow-up care included laboratory tests and abdominal ultrasound, which was repeated at regular intervals. Twenty-one children had Type I HAE and five suffered from Type II HAE. Clinical manifestations of the disease first occured in children when 2.5-12 years of age. Oedema formation primarily afflicted subcutaneous tissues. Mechanical trauma was identified as a precipitating factor in 20 patients. Pedigree analysis revealed 24 patients with relatives who suffered from HAE. Long-term prophylaxis with tranexamic acid or danazol was initiated in 11 patients; two children required short-term prophylaxis. No drug-related adverse effects were observed, except for one case of delayed menarche. Therapy improved serum complement parameters significantly and substantially reduced the frequency and severity of clinical episodes. Adequate prophylaxis and follow-up care can spare pediatric patients from oedematous attacks caused by HAE. Undesirable adverse effects can be avoided and the patient's quality of life enhanced considerably by administering the lowest effective drug dose. PMID:12144636

  17. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer.

    Science.gov (United States)

    Voorwinden, Jan S; Jaspers, Jan P C

    2016-06-01

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors that can predict which counselees are most likely to develop psychological problems after presymptomatic genetic testing. Counselees with a 50 % risk of BRCA1/2 or Lynch syndrome completed questionnaires at three time-points: after receiving a written invitation for a genetic counseling intake (T1), 2-3 days after receiving their DNA test result (T2), and 4-6 weeks later (T3). The psychological impact of the genetic test result was examined shortly and 4-6 weeks after learning their test result. Subsequently, the influence of various potentially prognostic factors on psychological impact were examined in the whole group. Data from 165 counselees were analyzed. Counselees with an unfavorable outcome did not have more emotional distress, but showed significantly more cancer worries 4-6 weeks after learning their test result. Prognostic factors for cancer worries after genetic testing were pre-existing cancer worries, being single, a high risk perception of getting cancer, and an unfavorable test result. Emotional distress was best predicted by pre-existing cancer worries and pre-existing emotional distress. The psychological impact of an unfavorable genetic test result appears considerable if it is measured as "worries about cancer." Genetic counselors should provide additional guidance to counselees with many cancer worries, emotional distress, a high risk perception or a weak social network. PMID:26475052

  18. Hereditary multiple exostoses: from genetics to clinical syndrome and complications

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    Vanhoenacker, Filip M.; Hul, Wim van; Wuyts, Wim; Willems, P.J.; Schepper, Arthur M. de

    2001-12-01

    Objective: To give an overview of genetic, clinical and radiological aspects in two families over four generations with known hereditary multiple exostoses (HME). Methods and material: After linkage analysis in both families to localize the defective gene, mutation analysis was performed in these genes to identify the underlying mutation. In the 31 affected individuals, location, number and morphology and evolution of exostosis, evolution of remodeling defects at the metaphysis, and the extent of possible complications were evaluated on clinical and imaging (plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI)) data over a lifetime period. Results and conclusions: Both families demonstrate the gene defect in the same EXT-2 gene locus on chromosome 11p. Exostoses are preferentially located in the lower extremity (hip, knee and lower leg), humerus, and forearm. Any other bone may be involved, except for the calvaria of the skull and the mandible. Exostoses are rather sessile than pedunculated. Exostosis is rarely present at birth but develops gradually and may persist to grow slowly after closure of the growth plates. Preferential expression of the remodeling defect was seen in the hip, distal femur (trumpet-shaped metaphysis) and forearm (shortening of the ulna with secondary bowing of the radius and development of a pseudo-Madelung deformity). These radiological manifestations start at the age of 4-5 years and become more obvious as the enchondral bone formation progresses with age. Reported complications in these families consist of local entrapment phenomenons (vessel, tendon, nerve), frictional bursitis, and sarcomatous transformation. MRI was able to suggest these complications and is the imaging technique of choice in the evaluation of symptomatic exostoses.

  19. Advocate's Viewpoint on Hereditary Breast/Ovarian Cancer

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    Kolling-Dandrieu Francisca

    2004-08-01

    Full Text Available Abstract This paper discusses the presentation I held at the symposium on genetics during the 4th European Breast Cancer Conference held in Hamburg in March 2004. Primarily, the goals and working methods of the advocacy group specialised in Hereditary Breast/Ovarian Cancer of the Dutch Breast Cancer Patient Organisation known as BorstkankerVereniging Nederland (BVN are explained. Furthermore, some specific individual problems that mutation carriers might encounter before and after BRCA1/2 susceptibility testing are discussed. These include: dilemmas in choosing preventive interventions, dealing with the psychological impact of knowing you are a mutation carrier, dealing with the social implications of being genetically at risk, an example of insurance discrimination. In addition, some controversial social and ethical issues that are currently under debate are highlighted, such as the issue of the European patenting of the breast cancer susceptibility genes BRCA1 and BRCA2. Since this topic could also become relevant for other gene-related diseases, society as a whole has to consider the ethical and social implications related to the patenting of human genes in general. Another ethical area of debate is the controversial issue of prenatal BRCA testing and the choice of pregnancy termination. Finally, the Working Party pleads for the international co-operation and exchange of data and experience among professionals as well as patients. It appears that professionals in different European countries tend to advise on different risk management strategies and treatments and as such, the Working Party strongly advocates the international standardisation of risk management and treatment of mutation carriers. In this respect, specific attention should be given to a group that has had a non-informative or negative BRCA test result, because this group is still considered to be at high risk to develop the disease.

  20. HEREDITARY CONNECTIVE TISSUE DISORDERS: NOMENCLATURE AND DIAGNOSTIC ALGORITHM

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    A. V. Klemenov

    2015-01-01

    Full Text Available Hereditary connective tissue disorders (HCTDs are a genetically and clinically diverse group of diseases, which encompasses common congenital disorders of fibrous connective tissue structures. Out of the whole variety of the clinical manifestations of NCTDs, only differentiated monogenic syndromes with the agreed guidelines for their diagnosis have been long the focus of the medical community’s attention. Many unclassified forms of the pathology (dysplasia phenotypes have been disregarded while assessing a person’s prognosis and defining treatment policy. With no clear definition of NCTDs or their approved diagnostic algorithm, it is difficult to study their real prevalence in the population, to compare literature data, and to constructively discuss various scientific and practical aspects of this disease. Efforts to systematize individual clinical types of NCTD and to formulate their diagnostic criteria are set forth in the All-Russian Research Society Expert Committee national guidelines approved in 2009 and revised in 2012. The paper gives current views on the nomenclature of NCTDs, considers diagnostic criteria for both classified monogenic syndromes (Marfan's syndrome, Ehlers–Danlos' syndrome, MASS phenotype, primary mitral valve prolapse, joint hypermobility syndrome and unclassified dysplasia phenotypes (MASS-like phenotype, marfanoid appearance, Ehlers–Danlos-like phenotype, benign joint hypermobility syndrome, unclassified phenotype. The above abnormalities are presented as a continuous list drawn up in the decreasing order of the degree of their clinical manifestations and prognostic value (the phenotypic continuum described by M.J. Glesby and R.E. Pyentz: from monogenic syndromes through dysplasia phenotypes to an unclassified phenotype. Emphasis is laid on the clinical NCTD identification difficulties associated with the lack of specificity of external and visceral markers of connective tissue asthenia and with the certain

  1. Management of acute attacks of hereditary angioedema: role of ecallantide

    Science.gov (United States)

    Duffey, Hannah; Firszt, Rafael

    2015-01-01

    Hereditary angioedema (HAE) is characterized as an episodic swelling disorder with autosomal dominant inheritance. Clinical features include nonpitting edema of external or mucosal body surfaces, and patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can lead to asphyxiation. Patients with HAE classically have no associated urticaria, which is often referred to as nonhistaminergic angioedema. Treatment for HAE involves long-term prophylaxis, short-term prophylaxis, and management of acute attacks. Up until the past few years, acute HAE episodes were predominately treated with supportive measures. Three classes of medications have recently been approved by the US Food and Drug Administration (FDA) for the management of acute HAE attacks. Ecallantide, a recombinant protein that acts as a reversible inhibitor of kallikrein, is currently indicated for acute attacks of HAE in those aged ≥12 years. In two randomized, double-blind, placebo-controlled, multicenter trials, EDEMA3 and EDEMA4, patients treated with 30 mg of ecallantide demonstrated statistically significant improvement in symptoms compared to those on placebo. In addition to its use as treatment for HAE, ecallantide has been used off label in the management of nonhistaminergic angioedema, not due to HAE. Ecallantide has shown promise in the treatment of these other forms; however, data are limited to mainly case reports at this time. Ecallantide is generally a safe and well-tolerated medication; however, based on reports of anaphylaxis, ecallantide does contain a black box warning. Due to the risk of anaphylaxis, ecallantide cannot be self-administered and must be given by a health care professional. Overall, ecallantide is a safe and effective medication for the treatment of acute attacks of HAE. PMID:25931832

  2. Circulating angiogenic cell dysfunction in patients with hereditary hemorrhagic telangiectasia.

    Directory of Open Access Journals (Sweden)

    Liana Zucco

    Full Text Available Hereditary hemorrhagic telangiectasia (HHT is an autosomal dominant vascular disorder. Circulating angiogenic cells (CACs play an important role in vascular repair and regeneration. This study was designed to examine the function of CACs derived from patients with HHT. Peripheral blood mononuclear cells (PBMNCs isolated from patients with HHT and age- and gender-matched healthy volunteers were assessed for expression of CD34, CD133 and VEGF receptor 2 by flow cytometry. PBMNCs were cultured to procure early outgrowth CACs. Development of endothelial cell (EC phenotype in CACs was analyzed by fluorescence microscopy. CAC apoptosis was assayed with Annexin V staining, and CAC migration assessed by a modified Boyden chamber assay. mRNA expression of endoglin (ENG, activin receptor-like kinase-1 (ACVLR1 or ALK1 and endothelial nitric oxide synthase (eNOS in CACs was measured by real time RT-PCR. The percentage of CD34+ cells in PBMNCs from HHT patients was significantly higher than in PBMNCs of healthy controls. CACs derived from patients with HHT not only showed a significant reduction in EC-selective surface markers following 7-day culture, but also a significant increase in the rate of basal apoptosis and blunted migration in response to vascular endothelial growth factor and stromal cell-derived factor-1. CACs from HHT patients expressed significantly lower levels of ENG, ALK1 and eNOS mRNAs. In conclusion, CACs from patients with HHT exhibited various functional impairments, suggesting a reduced regenerative capacity of CACs to repair the vascular lesions seen in HHT patients.

  3. Gastric angiodysplasia in a hereditary hemorrhagic telangiectasia type 2 patient

    Institute of Scientific and Technical Information of China (English)

    Minsu Ha; Yoon Jae Kim; Kwang An Kwon; Ki Baik Hahm; Mi-Jung Kim; Dong Kyu Kim; Young Jae Lee; S Paul Oh

    2012-01-01

    Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominantly inherited disease that occurs in approximately one in 5000 to 8000 people.Clinical diagnosis of HHT is made when a person presents three of the following four criteria:family history,recurrent nosebleeds,mucocutaneous telangiectasis,and arteriovenous malformations (AVM) in the brain,lung,liver and gastrointestinal (GI) tract.Although epistaxis is the most common presenting symptom,AVMs affecting the lungs,brain and GI tract provoke a more serious outcome.Heterozygous mutations in endoglin,activin receptor-like kinase 1 (ACVRL1; ALK1),and SMAD4,the genes involved in the transforming growth factor-β family signaling cascade,cause HHT.We report here the case of a 63 year-old male patient who presented melena and GI bleeding episodes,proven to be caused by bleeding from multiple gastric angiodysplasia.Esophagogastroduodenoscopy revealed multiple angiodysplasia throughout the stomach.Endoscopic argon plasma coagulation was performed to control bleeding from a gastric angiodysplasia.The patient has been admitted several times with episodes of hemoptysis and hematochezia.One year ago,the patient was hospitalized due to right-sided weakness,which was caused by left basal ganglia hemorrhage as the part of HHT presentation.In family history,the patient's mother and elder sister had died,due to intracranial hemorrhage,and his eldest son has been suffered from recurrent epistaxis for 20 years.A genetic study revealed a mutation in exon 3 of ALK1 (c.199C > T; p.Arg67Trp) in the proband and his eldest son presenting epistaxis.

  4. Hereditary multiple exostoses: from genetics to clinical syndrome and complications

    International Nuclear Information System (INIS)

    Objective: To give an overview of genetic, clinical and radiological aspects in two families over four generations with known hereditary multiple exostoses (HME). Methods and material: After linkage analysis in both families to localize the defective gene, mutation analysis was performed in these genes to identify the underlying mutation. In the 31 affected individuals, location, number and morphology and evolution of exostosis, evolution of remodeling defects at the metaphysis, and the extent of possible complications were evaluated on clinical and imaging (plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI)) data over a lifetime period. Results and conclusions: Both families demonstrate the gene defect in the same EXT-2 gene locus on chromosome 11p. Exostoses are preferentially located in the lower extremity (hip, knee and lower leg), humerus, and forearm. Any other bone may be involved, except for the calvaria of the skull and the mandible. Exostoses are rather sessile than pedunculated. Exostosis is rarely present at birth but develops gradually and may persist to grow slowly after closure of the growth plates. Preferential expression of the remodeling defect was seen in the hip, distal femur (trumpet-shaped metaphysis) and forearm (shortening of the ulna with secondary bowing of the radius and development of a pseudo-Madelung deformity). These radiological manifestations start at the age of 4-5 years and become more obvious as the enchondral bone formation progresses with age. Reported complications in these families consist of local entrapment phenomenons (vessel, tendon, nerve), frictional bursitis, and sarcomatous transformation. MRI was able to suggest these complications and is the imaging technique of choice in the evaluation of symptomatic exostoses

  5. Hereditary sensory and autonomic neuropathies: types II, III, and IV

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    Axelrod Felicia B

    2007-10-01

    Full Text Available Abstract The hereditary sensory and autonomic neuropathies (HSAN encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating. Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III, which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive.

  6. Hereditary Portfolio Optimization with Taxes and Fixed Plus Proportional Transaction Costs—Part II

    Directory of Open Access Journals (Sweden)

    Mou-Hsiung Chang

    2007-01-01

    Full Text Available This paper is the continuation of the paper entitled “Hereditary portfolio optimization with taxes and fixed plus proportional transaction costs I” that treats an infinite-time horizon hereditary portfolio optimization problem in a market that consists of one savings account and one stock account. Within the solvency region, the investor is allowed to consume from the savings account and can make transactions between the two assets subject to paying capital-gain taxes as well as a fixed plus proportional transaction cost. The investor is to seek an optimal consumption-trading strategy in order to maximize the expected utility from the total discounted consumption. The portfolio optimization problem is formulated as an infinite dimensional stochastic classical impulse control problem due to the hereditary nature of the stock price dynamics and inventories. This paper contains the verification theorem for the optimal strategy. It also proves that the value function is a viscosity solution of the QVHJBI.

  7. Hereditary Effects in Eccentric Compact Binary Inspirals to Third Post-Newtonian Order

    CERN Document Server

    Loutrel, Nicholas

    2016-01-01

    While there has been much success in understanding the orbital dynamics and gravitational wave emission of eccentric compact binaries in the post-Newtonian formalism, some problems still remain. The largest of these concerns hereditary effects: non-linear phenomena related to the scattering off of the background curved spacetime (tails) and to the generation of gravitational waves by gravitational waves (memory). Currently, these hereditary effects are only known numerically for arbitrary eccentricity through infinite sums of Bessel functions, with closed-form, analytic results only available in the small eccentricity limit. We here calculate, for the first time, closed-form, analytic expressions for all hereditary effects to third post-Newtonian order in binaries with arbitrary eccentricity. For the tails, we first asymptotically expand all Bessel functions in high eccentricity and find a superasymptotic series for each enhancement factor, accurate to better than $10^{-3}$ relative to post-Newtonian numerica...

  8. Urinary excretion of biomarkers of oxidatively damaged DNA and RNA in hereditary hemochromatosis

    DEFF Research Database (Denmark)

    Broedbaek, Kasper; Poulsen, Henrik E; Weimann, Allan; Kom, Ghainsom D; Schwedhelm, Edzard; Nielsen, Peter; Böger, Rainer H

    2009-01-01

    after phlebotomy treatment the excretion of the RNA oxidation product 8-oxoGuo returned to control values and the excretion of the DNA product 8-oxo-7,8-dihydro-2'-deoxyguanosine was reduced by 30%. In patients with hereditary hemochromatosis oxidative stress on nucleic acids is an important feature of......Oxidatively generated damage to nucleic acids is considered to play a significant role in carcinogenesis, and it has been shown that people with hereditary hemochromatosis are at increased risk of cancer. In this study we used a new refined liquid chromatography-tandem mass spectrometry method to...... measure the urinary excretion of oxidatively generated 8-oxo-7,8-dihydroguanine and related 2'-deoxyribonucleoside and ribonucleoside derivatives in hereditary hemochromatosis patients, and we investigated the effect of treatment on the levels of these modifications. The study was carried out as a...

  9. The effect of long-term danazol prophylaxis on liver function in hereditary angioedema?a longitudinal study

    OpenAIRE

    Farkas, Henriette; Czaller, Ibolya; Csuka, Dorottya; Vas, Anikó; Valentin, Szilvia; Varga, Lilian; Széplaki, Gábor; Jakab, László; Füst, George; Prohászka, Zoltán; Harmat, George; Visy, Beata; Karádi, István

    2009-01-01

    Abstract Background Danazol is a drug most widely used for the prophylaxis of hereditary angioedema resulting from the deficiency of the C1-inhibitor. Potential hepatotoxic or liver tumor-inducing side effects of long-term danazol prophylaxis have been investigated during the follow-up of hereditary angioedema patients. Methods Characteristic parameters of liver function (including bilirubin, GOT, GPT, ?GT...

  10. Prevalence of pulmonary arteriovenous malformations (PAVMs) and occurrence of neurological symptoms in patients with hereditary haemorrhagic telangiectasia (HHT)

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Oxhøj, H; Andersen, P E;

    2000-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease. HHT is characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs) and neurological symptoms.......Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease. HHT is characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs) and neurological symptoms....

  11. Human parvovirus B19-induced aplastic crisis in an adult patient with hereditary spherocytosis: a case report and review of the literature

    OpenAIRE

    Kobayashi, Yujin; Hatta, Yoshihiro; Ishiwatari, Yusaku; Kanno, Hitoshi; Takei, Masami

    2014-01-01

    Background Although there are several case reports of human parvovirus B19 infection in patients with hereditary spherocytosis, no systematic reviews of adult patients with hereditary spherocytosis with human parvovirus B19 infection have been published as clinical case reports. In this study, we report a case of aplastic crisis due to human parvovirus B19 infection in an adult patient with hereditary spherocytosis. Case presentation A 33-year-old woman with hereditary spherocytosis and galls...

  12. Hereditary cancer risk assessment: insights and perspectives for the Next-Generation Sequencing era

    Directory of Open Access Journals (Sweden)

    Israel Gomy

    2016-01-01

    Full Text Available Abstract Hereditary cancer risk assessment is a multidisciplinary and dynamic process, with the purpose of estimating probabilities of germline mutations in cancer susceptibility genes and assessing empiric risks of cancer based on personal and family histories, in order to offer clinical and molecular diagnoses and clinical management based on these risks. Genetic tests are available and most of them are reimbursed by insurance companies, although they are generally not covered by the public health systems of developing countries. More recently, molecular diagnosis of hereditary cancer is feasible through next-generation sequencing (NGS panels. Here we review the benefits and limitations of NGS technologies in the clinical practice.

  13. Diode laser treatment and clinical management of multiple oral lesions in patients with hereditary haemorrhagic telangiectasia.

    Science.gov (United States)

    Favia, G; Tempesta, A; Limongelli, L; Suppressa, P; Sabbà, C; Maiorano, E

    2016-05-01

    Hereditary haemorrhagic telangiectasia (HHT) is rare, and characterised by vascular dysplasia that leads to various symptoms including visceral arteriovenous malformations and mucocutaneous telangiectatic lesions. Our aim was to describe the clinical features and options for the treatment of multiple oral lesions, and to illustrate the efficacy of the diode laser in the treatment of early (occlusal plates were sometimes used to reduce the incidence of new lesions caused by dental trauma. The treatment of oral telangiectatic lesions is still being debated, and it is important to improve quality of life for patients. Diode laser surgery could be an effective treatment for oral lesions in those with hereditary haemorrhagic telangiectasia. PMID:26360009

  14. Hereditary cancer risk assessment: insights and perspectives for the Next-Generation Sequencing era.

    Science.gov (United States)

    Gomy, Israel; Diz, Maria Del Pilar Estevez

    2016-05-13

    Hereditary cancer risk assessment is a multidisciplinary and dynamic process, with the purpose of estimating probabilities of germline mutations in cancer susceptibility genes and assessing empiric risks of cancer based on personal and family histories, in order to offer clinical and molecular diagnoses and clinical management based on these risks. Genetic tests are available and most of them are reimbursed by insurance companies, although they are generally not covered by the public health systems of developing countries. More recently, molecular diagnosis of hereditary cancer is feasible through next-generation sequencing (NGS) panels. Here we review the benefits and limitations of NGS technologies in the clinical practice. PMID:27192130

  15. Novel germline c-MET mutation in a family with hereditary papillary renal carcinoma

    DEFF Research Database (Denmark)

    Wadt, Karin; Gerdes, Anne-Marie; Hansen, Thomas V O;

    2012-01-01

    Hereditary papillary renal carcinoma (HPRC) is a highly penetrant hereditary renal cancer syndrome caused by germline missense mutations in the c-MET proto-oncogene. HPRC is clinically characterized by multiple bilateral papillary renal-cell carcinomas. Here we report a family with a novel missense...... mutation in c-MET. The original pathology report of four primary kidney cancers (1988-1997) revealed renal-cell carcinoma. A revised report described multiple adenomas and papillary renal-cell carcinomas with focal clear cells and a mixture of type 1 and type 2 pattern, emphasizing the importance of...

  16. Hereditary cancer risk assessment: insights and perspectives for the Next-Generation Sequencing era

    Science.gov (United States)

    Gomy, Israel; Diz, Maria Del Pilar Estevez

    2016-01-01

    Abstract Hereditary cancer risk assessment is a multidisciplinary and dynamic process, with the purpose of estimating probabilities of germline mutations in cancer susceptibility genes and assessing empiric risks of cancer based on personal and family histories, in order to offer clinical and molecular diagnoses and clinical management based on these risks. Genetic tests are available and most of them are reimbursed by insurance companies, although they are generally not covered by the public health systems of developing countries. More recently, molecular diagnosis of hereditary cancer is feasible through next-generation sequencing (NGS) panels. Here we review the benefits and limitations of NGS technologies in the clinical practice. PMID:27192130

  17. Ethical dilemmas in genetic testing: examples from the Cuban program for predictive diagnosis of hereditary ataxias.

    Science.gov (United States)

    Mariño, Tania Cruz; Armiñán, Rubén Reynaldo; Cedeño, Humberto Jorge; Mesa, José Miguel Laffita; Zaldivar, Yanetza González; Rodríguez, Raúl Aguilera; Santos, Miguel Velázquez; Mederos, Luis Enrique Almaguer; Herrera, Milena Paneque; Pérez, Luis Velázquez

    2011-06-01

    Predictive testing protocols are intended to help patients affected with hereditary conditions understand their condition and make informed reproductive choices. However, predictive protocols may expose clinicians and patients to ethical dilemmas that interfere with genetic counseling and the decision making process. This paper describes ethical dilemmas in a series of five cases involving predictive testing for hereditary ataxias in Cuba. The examples herein present evidence of the deeply controversial situations faced by both individuals at risk and professionals in charge of these predictive studies, suggesting a need for expanded guidelines to address such complexities. PMID:21264501

  18. Cardiac arrest after anesthetic management in a patient with hereditary sensory autonomic neuropathy type IV

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    Ergül Yakup

    2011-01-01

    Full Text Available Hereditary sensory autonomic neuropathy type IV is a rare disorder with an autosomal recessive transmission and characterized by self-mutilation due to a lack in pain and heat sensation. Recurrent hyperpyrexia and anhydrosis are seen in patients as a result of a lack of sweat gland innervation. Self-mutilation and insensitivity to pain result in orthopedic complications and patients undergone recurrent surgical interventions with anesthesia. However, these patients are prone to perioperative complications such as hyperthermia, hypothermia, and cardiac complications like bradycardia and hypotension. We report a 5-year-old boy with hereditary sensory autonomic neuropathy type IV, developing hyperpyrexia and cardiac arrest after anesthesia.

  19. Hereditary angioedema type 2 presented as an orbital complication of acute rhinosinusitis.

    Science.gov (United States)

    Somuk, Battal Tahsin; Göktas, Göksel; Özer, Samet; Sapmaz, Emrah; Bas, Yalcın

    2016-03-01

    Hereditary angioedema is an autosomal dominant and life-threatening disorder characterized by recurrent episodes of non-pitting edema affecting the skin, respiratory system and digestive tracts and caused by a congenital deficiency or function defect of the C1 esterase inhibitor. Preseptal cellulitis is defined as an infection of the tissues of the anterior orbital septum. It is generally caused by complications from an upper respiratory tract infection, dacryocystitis, dermal infection, and, rarely, sinusitis. The disease presents with orbital pain, edema on the eyelids, erythema, and fever. In this case, a child with hereditary angioedema type 2 who presented as mimicking a complication of acute sinusitis is discussed. PMID:26857308

  20. Diagnosis and treatment of hereditary angioedema with normal C1 inhibitor

    Directory of Open Access Journals (Sweden)

    Bork Konrad

    2010-07-01

    Full Text Available Abstract Until recently it was assumed that hereditary angioedema is a disease that results exclusively from a genetic deficiency of the C1 inhibitor. In 2000, families with hereditary angioedema, normal C1 inhibitor activity and protein in plasma were described. Since then numerous patients and families with that condition have been reported. Most of the patients by far were women. In many of the affected women, oral contraceptives, hormone replacement therapy containing estrogens, and pregnancies triggered the clinical symptoms. Recently, in some families mutations in the coagulation factor XII (Hageman factor gene were detected in the affected persons.

  1. Knowledge about hereditary nonpolyposis colorectal cancer; mutation carriers and physicians at equal levels

    DEFF Research Database (Denmark)

    Domanska, Katarina; Carlsson, Christina; Bendahl, Pär-Ola;

    2009-01-01

    BACKGROUND: Identification and adequate management of individuals at risk for hereditary nonpolyposis colorectal cancer (HNPCC) is crucial since surveillance programmes reduce morbidity and mortality. We investigated knowledge about key features of HNPCC in at risk individuals and physicians in...... suggested a later starting age for surveillance than recommended. CONCLUSION: The finding of similar levels of knowledge about key features of HNPCC in at risk individuals and physicians reflect the challenge physicians face in keeping up to date on hereditary cancer and may have implications for the...... clinical management and professional relations with HNPCC family members....

  2. Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia

    Directory of Open Access Journals (Sweden)

    MacKie Iain

    2008-11-01

    Full Text Available Abstract The hereditary dentine disorders, dentinogenesis imperfecta (DGI and dentine dysplasia (DD, comprise a group of autosomal dominant genetic conditions characterised by abnormal dentine structure affecting either the primary or both the primary and secondary dentitions. DGI is reported to have an incidence of 1 in 6,000 to 1 in 8,000, whereas that of DD type 1 is 1 in 100,000. Clinically, the teeth are discoloured and show structural defects such as bulbous crowns and small pulp chambers radiographically. The underlying defect of mineralisation often results in shearing of the overlying enamel leaving exposed weakened dentine which is prone to wear. Currently, three sub-types of DGI and two sub-types of DD are recognised but this categorisation may change when other causative mutations are found. DGI type I is inherited with osteogenesis imperfecta and recent genetic studies have shown that mutations in the genes encoding collagen type 1, COL1A1 and COL1A2, underlie this condition. All other forms of DGI and DD, except DD-1, appear to result from mutations in the gene encoding dentine sialophosphoprotein (DSPP, suggesting that these conditions are allelic. Diagnosis is based on family history, pedigree construction and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Differential diagnoses include hypocalcified forms of amelogenesis imperfecta, congenital erythropoietic porphyria, conditions leading to early tooth loss (Kostmann's disease, cyclic neutropenia, Chediak-Hegashi syndrome, histiocytosis X, Papillon-Lefevre syndrome, permanent teeth discolouration due to tetracyclines, Vitamin D-dependent and vitamin D-resistant rickets. Treatment involves removal of sources of infection or pain, improvement of aesthetics and protection of the posterior teeth from wear. Beginning in infancy, treatment usually continues into adulthood with a

  3. Hereditary multiple exostosis with secondary malignization: case report

    Energy Technology Data Exchange (ETDEWEB)

    Coutinho, A.M.N.; Pitella, F.A.; Coura Filho, G.B.; Costa, P.L.A.; Ono, C.R.; Watanabe, T.; Sapienza, M.T.; Hironaka, F.; Cerri, G.G.; Buchpiguel, C.A. [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Radiologia. Centro de Medicna Nuclear

    2008-07-01

    Full text: Introduction: Hereditary Multiple Exostosis (HME) or multiple osteochondromatosis is a skeletal development anomaly which is characterized by generalized exostoses in the bones, mainly in long bone metaphyses, appearing during childhood and adolescence. The transmission is autosomal dominant, its prevalence varies from 1/50,000 to 9/1,000,000 in Europe, and around 10% of cases show no family history. Case Report: Description of an HME case with two secondary malignization episodes. The data was taken from the patient's chart and from imaging exams from the hospital files. WASB, a 19-year-old male, hospitalized after being pre-diagnosed with HME and complaints of bone-consistent mass in the right gluteal region and a lump in the posterior region of the right leg, associated to multiple bone lumps all over the body. A magnetic resonance imaging (MRI) was performed along with a bone scintillography with {sup 99m}Tc-MDP which showed multiple osteogenic lesions in the thorax, pelvic bones and long bones with periarticular prevalence in the lower limbs. The suspicion of malignancy in the right iliac area was raised due to the MRI result and to the higher intensity captured in the scintillography, confirming chondrosarcoma grade I of malignancy in the biopsy. The patient suffered interileo abdominalis amputation of the right lower limb with good evolution and control scintillography performed after 1 and 1,5 years. In the second controlling procedure, the patient complained about pain in the left knee, and a MRI suggested a new secondary malignization. The hypothesis of a head of left fibula osteochondroma with signs of aggressiveness was confirmed following surgery. Discussion: In HME, the exostoses grow along with the individual, ceasing with the epiphyseal fusion. The growth of these formations after skeletal maturation suggests activity of exostoses and, in most times, it is a sign of malignant transformation, which turns almost every time into

  4. Surgical management of hand deformities in hereditary dystrophic epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    Panajotović Ljubomir

    2003-01-01

    Full Text Available In the period 1996-2001 in the Clinic for Plastic Surgery and Burns of the Military Medical Academy, 18 patients. 12 male and 6 female, with hereditary dystrophic epidermolysis bullosa (HDEB and hand deformities were surgically treated, to achieve the complete separation of fingers, correction of the thumb adduction contracture and flexion or extension contracture of finger joints. The period of wound healing on flat surfaces after surgery, and the period between two operations was estimated. The most common deformity was the flexion contractures of metacarpophalangeal (MP joints (45% and one or both interphalangeal (IP joints (types A1, A2. In 20% of the hands MP joint was streched with the flexion contracture in distal interphalangeal (DIP or both IP joints (types B1, B2. In 35% of hands MP joint was in hyperextension with folded proximal interphalangeal (PIP or both IP joints (C1 i C2. The adduction deformity of the thumb type 1, without the possibility of abduction, was present in 15%, type 2, when the thumb was placed above the palm in 60% and type 3, when the thumb was fused in the palm in 25%. Pseudosyndactyly of the first degree (till PIP joint was found in 30% of hands, the second degree (till DIP joint in 25%, and the third degree (the whole finger length in 45% of hands. Fingers were completely separated and stretched surgically. The period of spontaneous healing was 15 days on the average. EBDC represents great medical and social problem that requires multidisciplinary approach of physicians of various specialties (surgeons, dermatologists, pediatrists, geneticists, nutritionists physiatrists, ophtalmologists, dentists, ENT, as well as specially trained persons and families. The efficient specific systemic therapy aiming to increase the skin resistence to mechanical trauma does not exist yet, and should be developed in the field of gene therapy. The surgical correction of hand deformities, acrylate glove use in the longer post

  5. Management of acute attacks of hereditary angioedema: role of ecallantide

    Directory of Open Access Journals (Sweden)

    Duffey H

    2015-04-01

    Full Text Available Hannah Duffey,1 Rafael Firszt1,2 1Department of Pediatrics, 2Division of Allergy, Immunology and Rheumatology, University of Utah, Salt Lake City, UT, USA Abstract: Hereditary angioedema (HAE is characterized as an episodic swelling disorder with autosomal dominant inheritance. Clinical features include nonpitting edema of external or mucosal body surfaces, and patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can lead to asphyxiation. Patients with HAE classically have no associated urticaria, which is often referred to as nonhistaminergic angioedema. Treatment for HAE involves long-term prophylaxis, short-term prophylaxis, and management of acute attacks. Up until the past few years, acute HAE episodes were predominately treated with supportive measures. Three classes of medications have recently been approved by the US Food and Drug Administration (FDA for the management of acute HAE attacks. Ecallantide, a recombinant protein that acts as a reversible inhibitor of kallikrein, is currently indicated for acute attacks of HAE in those aged 12 years. In two randomized, double-blind, placebo-controlled, multicenter trials, EDEMA3 and EDEMA4, patients treated with 30 mg of ecallantide demonstrated statistically significant improvement in symptoms compared to those on placebo. In addition to its use as treatment for HAE, ecallantide has been used off label in the management of nonhistaminergic angioedema, not due to HAE. Ecallantide has shown promise in the treatment of these other forms; however, data are limited to mainly case reports at this time. Ecallantide is generally a safe and well-tolerated medication; however, based on reports of anaphylaxis, ecallantide does contain a black box warning. Due to the risk of anaphylaxis, ecallantide cannot be self-administered and must be given by a health care professional. Overall, ecallantide is a safe and effective medication for the

  6. Hereditary angioedema in childhood: an approach to management.

    Science.gov (United States)

    Ebo, Didier G; Verweij, Marjoke M; De Knop, Kathleen J; Hagendorens, Margo M; Bridts, Chris H; De Clerck, Luc S; Stevens, Wim J

    2010-08-01

    Hereditary angioedema (HAE) is an inherited disorder characterized by recurrent, circumscribed, non-pitting, non-pruritic, and rather painful subepithelial swelling of sudden onset, which fades during the course of 48-72 hours, but can persist for up to 1 week. Lesions can be solitary or multiple, and primarily involve the extremities, larynx, face, esophagus, and bowel wall. Patients with HAE experience angioedema because of a defective control of the plasma kinin-forming cascade that is activated through contact with negatively charged endothelial macromolecules leading to binding and auto-activation of coagulation factor XII, activation of prekallikrein to kallikrein by factor XIIa, and cleavage of high-molecular-weight kininogen by kallikrein to release the highly potent vasodilator bradykinin. Three forms of HAE have currently been described. Type I and type II HAE are rare autosomal dominant diseases due to mutations in the C1-inhibitor gene (SERPING1). C1-inhibitor mutations that cause type I HAE occur throughout the gene and result in truncated or misfolded proteins with a deficiency in the levels of antigenic and functional C1-inhibitor. Mutations that cause type II HAE generally involve exon 8 at or adjacent to the active site, resulting in an antigenically intact but dysfunctional mutant protein. In contrast, type III HAE (also called estrogen-dependent HAE) is characterized by normal C1-inhibitor activity. The diagnosis of HAE is suggested by a positive family history, the absence of accompanying pruritus or urticaria, the presence of recurrent gastrointestinal attacks of colic, and episodes of laryngeal edema. Estrogens may exacerbate attacks, and in some patients attacks are precipitated by trauma, inflammation, or psychological stress. For type I and type II HAE, diminished C4 concentrations are highly suggestive for the diagnosis. Further laboratory diagnosis depends on demonstrating a deficiency of C1-inhibitor antigen (type I) in most kindreds

  7. Hereditary angioedema: epidemiology, management, and role of icatibant.

    Science.gov (United States)

    Ghazi, Aasia; Grant, J Andrew

    2013-01-01

    Hereditary angioedema (HAE) is an autosomal dominant, potentially life-threatening condition, manifesting as recurrent and self-limiting episodes of facial, laryngeal, genital, or peripheral swelling with abdominal pain secondary to intra-abdominal edema. The estimated prevalence of HAE in the general population is one individual per 50,000, with reported ranges from 1:10,000 to 1:150,000, without major sex or ethnic differences. Various treatment options for acute attacks and prophylaxis of HAE are authorized and available in the market, including plasma-derived (Berinert®, Cinryze®, and Cetor®) and recombinant (Rhucin® and Ruconest™) C1 inhibitors, kallikrein inhibitor-ecallantide (Kalbitor®), and bradykinin B2 receptor antagonist-icatibant (Firazyr®). Some of these drugs are used only to treat HAE attacks, whereas others are only approved for prophylactic therapies and all of them have improved disease outcomes due to their different mechanisms of action. Bradykinin and its binding to B2 receptor have been demonstrated to be responsible for most of the symptoms of HAE. Thus icatibant (Firazyr®), a bradykinin B2 receptor antagonist, has proven to be an effective and more targeted treatment option and has been approved for the treatment of acute attacks of HAE. Rapid and stable relief from symptoms of cutaneous, abdominal, or laryngeal HAE attacks has been demonstrated by 30 mg of icatibant in Phase III clinical trials. Self-resolving mild to moderate local site reactions after subcutaneous injection of icatibant were observed. Icatibant is a new, safe, and effective treatment for acute attacks of HAE. HAE has been reported to result in enormous humanistic burden to patients, affecting both physical and mental health, with a negative impact on education, career, and work productivity, and with substantial economic burdens. The timely and proper use of disease-specific treatments could improve patients' quality of life, reduce the disease

  8. Congenital hereditary endothelial dystrophy with progressive sensorineural deafness (Harboyan syndrome

    Directory of Open Access Journals (Sweden)

    Abramowicz Marc

    2008-10-01

    Full Text Available Abstract Harboyan syndrome is a degenerative corneal disorder defined as congenital hereditary endothelial dystrophy (CHED accompanied by progressive, postlingual sensorineural hearing loss. To date, 24 cases from 11 families of various origin (Asian Indian, South American Indian, Sephardi Jewish, Brazilian Portuguese, Dutch, Gypsy, Moroccan, Dominican have been reported. More than 50% of the reported cases have been associated with parental consanguinity. The ocular manifestations in Harboyan syndrome include diffuse bilateral corneal edema occurring with severe corneal clouding, blurred vision, visual loss and nystagmus. They are apparent at birth or within the neonatal period and are indistinguishable from those characteristic of the autosomal recessive CHED (CHED2. Hearing deficit in Harboyan is slowly progressive and typically found in patients 10–25 years old. There are no reported cases with prelinglual deafness, however, a significant hearing loss in children as young as 4 years old has been detected by audiometry, suggesting that hearing may be affected earlier, even at birth. Harboyan syndrome is caused by mutations in the SLC4A11 gene located at the CHED2 locus on chromosome 20p13-p12, indicating that CHED2 and Harboyan syndrome are allelic disorders. A total of 62 different SLC4A11 mutations have been reported in 98 families (92 CHED2 and 6 Harboyan. All reported cases have been consistent with autosomal recessive transmission. Diagnosis is based on clinical criteria, detailed ophthalmological assessment and audiometry. A molecular confirmation of the clinical diagnosis is feasible. A variety of genetic, metabolic, developmental and acquired diseases presenting with clouding of the cornea should be considered in the differential diagnosis (Peters anomaly, sclerocornea, limbal dermoids, congenital glaucoma. Audiometry must be performed to differentiate Harboyan syndrome from CHED2. Autosomal recessive types of CHED (CHED2 and

  9. Tumores colorretais hereditários Hereditary colorectal tumors

    Directory of Open Access Journals (Sweden)

    Benedito Mauro Rossi

    1998-08-01

    áveis pela respectiva doença ou pela proteína produto dos mesmos. É de suma importância uma abordagem multidisciplinar de pacientes portadores de FAP ou HNPCC, pois existe uma preocupação ética muito grande na realização dos testes genéticos de predisposição, considerando suas conseqüências psicológicas e sociais.About 15% of the colorectal tumors are hereditary. There are two main groups: the familiar adenomatous polyposis (FAP and the non-polyposis colorectal cancer (HNPCC, both autosomal dominant diseases. Patients with FAP present hundreds to thousands of adenomas in colorectum. usually after puberty. The cause of FAP is mutation of the adenomatous polyposis coli (APC gene, located on long arm of chromosome 5 (5q. Patients who have not undergone to colectomy, the only treatment avaiable, will develop colorectal cancer and die at the age of 45 years. Extracolonic manifestations can occur: gastric and small bowel adenomas, soft tissue tumors, retinal pigmentation. osteomas. Patients with HNPCC do not present hundreds of benign polyps, but already a solitary colorectal cancer: This disease is caused by mutations in one of the several mismatch repair genes (hMSH2, hMLHI, hPMSI, hPMS2, hPMS6/GTBP. The average age of the diagnosis is 45 years and usually the disease produces cancer in the right colon. Other carcinomas can occur: endometrial, stomach, pancreas and others. Prophylactic surgery in asymptomatic gene carriers are controversial. Nowadays it is possible to identify asymptomatic genes carriers of FAP and HNPCC by genetic testing. The analysis can be done by direct gene sequencing or by in vitro synthesized protein assay (IVSP, which finds defective truncate proteins. Genetic testing for hereditary forms of colorectal cancer requires not only an appropriate laboratory, but genetic counseling with an ethical multidisciplinary approach considering the psychological and social consequences.

  10. Ocular findings in quarter horses with hereditary equine regional dermal asthenia

    Science.gov (United States)

    The objective of this study was to compare ocular structures of Quarter Horses homozygous for hereditary equine regional dermal asthenia (HERDA) with those of Quarter Horses not affected by HERDA (control horses) and to determine the frequency of new corneal ulcers for horses with and without HERDA ...

  11. The hereditary progressive muscular dystrophy type 2A (calpainopathy: a clinical case

    Directory of Open Access Journals (Sweden)

    D. A. Grishina

    2015-05-01

    Full Text Available Presents clinical case the hereditary progressive muscular dystrophy type 2A (calpainopathy. Shows diagnostic difficulties and feature of presents clinical observations. This case is significance, as in the domestic scientific literature presents few articles on clinical examples of this muscle pathology.

  12. Hereditary non-polyposis colorectal cancer: clinical features and survival. Results from the Danish HNPCC register

    DEFF Research Database (Denmark)

    Myrhøj, T; Bisgaard, M L; Bernstein, Inge Thomsen; Svendsen, L B; Søndergaard, J O; Bülow, Steffen

    1997-01-01

    BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome characterized by the development of colorectal cancer (CRC) and other carcinomas. Our aim was to evaluate tumour parameters and survival in HNPCC. METHODS: One hundred and eight Danish HNPCC patients...

  13. Radiological features of bilateral hereditary micro-epiphyseal dysplasia - a distinct entity in the skeletal dysplasias

    NARCIS (Netherlands)

    Morstert, AK; Dijkstra, PF; van Horn, [No Value; Jansen, BRH; Heutink, P; Lindhout, D

    2002-01-01

    Aim: To prove that bilateral hereditary micro-epiphyseal dysplasia (BHMED), first described by Elsbach in 1959 [1], is a distinct disorder radiologically as well as clinically, compared with multiple epiphyseal dysplasia (MED). Material and Methods: We used the data of the revised pedigree with 84 f

  14. The Regulatory Role of Nuclear Factor Kappa B in the Heart of Hereditary Hypertriglyceridemic Rat

    Czech Academy of Sciences Publication Activity Database

    Vranková, S.; Barta, A.; Klimentová, J.; Dovinová, I.; Líšková, Silvia; Dobešová, Zdenka; Pecháňová, O.; Kuneš, Jaroslav; Zicha, Josef

    2016-01-01

    Roč. 2016 (2016), s. 9814038. ISSN 1942-0900 R&D Projects: GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : nuclear factor-kB * nitric oxide * reactive oxygen species * heart * hereditary hypertriglyceridemic rats Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.516, year: 2014

  15. Awareness of endometrial cancer risk and compliance with screening in hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ketabi, Zohreh; Mosgaard, Berit J; Gerdes, Anne-Marie; Ladelund, Steen; Bernstein, Inge T

    2012-01-01

    Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a 40-60% lifetime risk for endometrial cancer. Guidelines in Denmark recommend gynecologic screening for female members of families with HNPCC. We estimated the knowledge of endometrial cancer risk and identified possible predictors...... of compliance with the screening among women from families with HNPCC....

  16. Hereditary Deafness in a Former Fishing Village on the Dutch Coast

    Science.gov (United States)

    Nyst, Victoria A. S.

    2016-01-01

    In communities with an increased prevalence of hereditary deafness, social, and linguistic adaptations are found in response. Aulbers (1959) describes a high prevalence of deafness in a fishing village on the Dutch coast: Katwijk aan Zee. This article aims to assess the current prevalence of deafness in Katwijk, as well as the current sign…

  17. Risk of gynecologic cancers in Danish hereditary non-polyposis colorectal cancer families

    DEFF Research Database (Denmark)

    Boilesen, Astrid Elisabeth Bruun; Bisgaard, Marie Luise; Bernstein, Inge

    2008-01-01

    OBJECTIVE: Women in hereditary non-polyposis colorectal cancer (HNPCC) families have an elevated risk of endometrial and ovarian cancer. The risk in Lynch syndrome families with known mutations in mismatch repair genes (MMR genes) seems to be higher than in familial colorectal cancer (CRC) famili...

  18. Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer

    DEFF Research Database (Denmark)

    Movahedi, Mohammad; Bishop, D Timothy; Macrae, Finlay;

    2015-01-01

    PURPOSE: In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patie...

  19. Hereditary thrombophilia and recurrent pregnancy loss: a retrospective cohort study of pregnancy outcome and obstetric complications

    DEFF Research Database (Denmark)

    Lund, M; Nielsen, H S; Hviid, T V;

    2010-01-01

    The association among hereditary thrombophilia, recurrent pregnancy loss (RPL) and obstetric complications is yet uncertain. The objective of the study was to assess the prognostic value of the factor V Leiden (FVL) and prothrombin (PT) mutations for the subsequent chance of live birth for women...

  20. Mismatch repair defective breast cancer in the hereditary nonpolyposis colorectal cancer syndrome

    DEFF Research Database (Denmark)

    Jensen, Uffe Birk; Sunde, Lone; Timshel, Susanne; Halvarsson, Britta; Nissen, Anja; Bernstein, Inge; Nilbert, Mef

    2010-01-01

    Whether or not breast cancer can be a feature of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome has been debated. In order to clarify if defective mismatch repair (MMR) may indeed play a role in breast cancer, we used the Danish HNPCC register to identify all breast cancers that o...

  1. Sarcomas associated with hereditary nonpolyposis colorectal cancer: broad anatomical and morphological spectrum

    DEFF Research Database (Denmark)

    Nilbert, Mef; Therkildsen, Christina; Nissen, Anja; Akerman, Måns; Bernstein, Inge

    2009-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is primarily linked to colorectal and endometrial cancer, but is associated with a broad tumor spectrum. Though not formally part of the syndrome, occasional sarcomas have been reported in individuals with HNPCC. We used the national Danish HNPCC-...

  2. Rapidly deteriorating course in Dutch hereditary spastic paraplegia type 11 patients

    NARCIS (Netherlands)

    de Bot, Susanne T.; Burggraaff, Rogier C.; Herkert, Johanna C.; Schelhaas, Helenius J.; Post, Bart; Diekstra, Adinda; van Vliet, Reinout O.; van der Knaap, Marjo S.; Kamsteeg, Erik-Jan; Scheffer, Hans; van de Warrenburg, Bart P.; Verschuuren-Bemelmans, Corien C.; Kremer, Hubertus P. H.

    2013-01-01

    Although SPG11 is the most common complicated hereditary spastic paraplegia, our knowledge of the long-term prognosis and life expectancy is limited. We therefore studied the disease course of all patients with a proven SPG11 mutation as tested in our laboratory, the single Dutch laboratory providin

  3. Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background.

    NARCIS (Netherlands)

    Hudson, G.; Carelli, V.; Spruijt, L.; Gerards, M.; Mowbray, C.; Achilli, A.; Pyle, A.; Elson, J.; Howell, N.; Morgia, C. La; Valentino, M.L.; Huoponen, K.; Savontaus, M.L.; Nikoskelainen, E.; Sadun, A.A.; Salomao, S.R.; Belfort Jr, R.; Griffiths, P.; Man, P.Y.; Coo, R.F. de; Horvath, R.; Zeviani, M.; Smeets, H.J.M.; Torroni, A.; Chinnery, P.F.

    2007-01-01

    Leber hereditary optic neuropathy (LHON) is due primarily to one of three common point mutations of mitochondrial DNA (mtDNA), but the incomplete penetrance implicates additional genetic or environmental factors in the pathophysiology of the disorder. Both the 11778G-->A and 14484T-->C LHON mutation

  4. miRNA expression profiling of formalin-fixed paraffin-embedded (FFPE hereditary breast tumors

    Directory of Open Access Journals (Sweden)

    Miljana Tanić

    2015-03-01

    Full Text Available Hereditary breast cancer constitutes only 5–10% of all breast cancer cases and is characterized by strong family history of breast and/or other associated cancer types. Only ~25% of hereditary breast cancer cases carry a mutation in BRCA1 or BRCA2 gene, while mutations in other rare high and moderate-risk genes and common low penetrance variants may account for additional 20% of the cases. Thus the majority of cases are still unaccounted for and designated as BRCAX tumors. MicroRNAs are small non-coding RNAs that play important roles as regulators of gene expression and are deregulated in cancer. To characterize hereditary breast tumors based on their miRNA expression profiles we performed global microarray miRNA expression profiling on a retrospective cohort of 80 FFPE breast tissues, including 66 hereditary breast tumors (13 BRCA1, 10 BRCA2 and 43 BRCAX, 10 sporadic breast carcinomas and 4 normal breast tissues, using Exiqon miRCURY LNA™ microRNA Array v.11.0. Here we describe in detail the miRNA microarray expression data and tumor samples used for the study of BRCAX tumor heterogeneity (Tanic et al., 2013 and biomarkers associated with positive BRCA1/2 mutation status (Tanic et al., 2014. Additionally, we provide the R code for data preprocessing and quality control.

  5. [From gene to disease; E-cadherin and hereditary diffuse gastric cancer

    NARCIS (Netherlands)

    Bruin, J.H.F.M. de; Ligtenberg, M.J.L.; Nagengast, F.M.; Krieken, J.H.J.M. van

    2003-01-01

    Hereditary diffuse gastric cancer (HDGC) is a rare autosomal dominant syndrome associated with an early-onset, histologically diffuse, signet ring cell type gastric cancer and the occurrence of cancer at other anatomical sites, i.e. breast, colon, prostate and ovary. Inactivating germline mutations

  6. Hereditary hemochromatosis (HFE) genotypes in heart failure: relation to etiology and prognosis

    DEFF Research Database (Denmark)

    Møller, Daniel Vega; Pecini, Redi; Gustafsson, Finn;

    2010-01-01

    It is believed that hereditary hemochromatosis (HH) might play a role in cardiac disease (heart failure (HF) and ischemia). Mutations within several genes are HH-associated, the most common being the HFE gene. In a large cohort of HF patients, we sought to determine the etiological role and the...

  7. Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations

    DEFF Research Database (Denmark)

    Wagenaar-Bos, Ineke G A; Drouet, Christian; Aygören-Pursun, Emel;

    2008-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The most widespread underlying genetic deficiency is a heterozygous deficiency of the serine protease inhibitor C1 esterase inhibitor (C1-Inh). In addition ...

  8. Safety of C1-Esterase Inhibitor in Acute and Prophylactic Therapy of Hereditary Angioedema

    DEFF Research Database (Denmark)

    Busse, Paula; Bygum, Anette; Edelman, Jonathan; Lumry, William; Machnig, Thomas; Martinez-Saguer, Inmaculada; Rojavin, Mikhail

    2014-01-01

    BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products...

  9. The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency

    DEFF Research Database (Denmark)

    Csuka, Dorottya; Munthe-Fog, Lea; Skjoedt, Mikkel-Ole; Kocsis, Andrea; Zotter, Zsuzsanna; Gál, Péter; Varga, Lilian; Farkas, Henriette; Füst, George; Garred, Peter

    Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) causes disturbances in the complement system. However, the influence of HAE-C1-INH on the lectin pathway of complement is unresolved. Thus, we studied the main initiator molecules, enzymes and regulators in the lectin pathway in...

  10. Mutational spectrum and phenotypes in Danish families with hereditary angioedema because of C1 inhibitor deficiency

    DEFF Research Database (Denmark)

    Bygum, A; Fagerberg, C R; Ponard, D; Monnier, N; Lunardi, J; Drouet, C

    2011-01-01

    Hereditary angioedema (HAE), type I and II, is an autosomal dominant disease with deficiency of functional C1 inhibitor protein causing episodic swellings of skin, mucosa and viscera. HAE is a genetically heterogeneous disease with more than 200 different mutations in the SERPING1 gene. A genotype...

  11. Membranous nephropathy in a patient with hereditary angioedema: a case report

    Directory of Open Access Journals (Sweden)

    Majoni Sandawana W

    2008-10-01

    Full Text Available Abstract Introduction Hereditary angioedema is the commonest inherited disorder of the complement system and has been associated with several immune glomerular diseases. A case of nephrotic syndrome and renal impairment due to idiopathic membranous glomerulonephritis in a patient with hereditary angioedema has not been described before. Case presentation We present the first reported case of the association of membranous nephropathy and hereditary angioedema in a 43-year-old male Caucasian patient who presented with acute intestinal angioedema, hypertension, acute pancreatitis, renal impairment and generalised body swelling due to severe nephrotic syndrome. We present the challenges involved in the clinical management of the patient. Conclusion This patient's presentation with severe nephrotic syndrome, renal impairment and hypertension required aggressive treatment of the membranous nephropathy given the high risk for progression to end stage renal failure. The contraindication to angiotensin converting enzyme inhibitors and angiotensin II receptor blockers in this patient, the lack of published evidence on the use of alkylating agents and other immunosuppressive agents in patients with hereditary angioedema and the lack of published data on the management of similar cases presented a clinical challenge in this patient's management.

  12. Treatment of hereditary angioedema with plasma-derived C1 inhibitor

    Directory of Open Access Journals (Sweden)

    Michael J Prematta

    2008-08-01

    Full Text Available Michael J Prematta, Tracy Prematta, Timothy J CraigSection of Allergy and Immunology, Penn State University, Milton S. Hershey Medical Center, PA, USABackground: Plasma-derived C1 inhibitor (C1-INH concentrate is a treatment option for acute hereditary angioedema (HAE attacks and is considered the standard-of-care in many countries, although it is not yet available in the United States. Studies are still being conducted to establish its safety and efficacy as required by the FDA.Objective: To review the medical literature to determine if C1-INH concentrate is a safe and effective treatment for acute HAE attacks.Methods: The following keywords were searched in PubMed and OVID: C1 esterase inhibitor, C1-inhibitor, C1 inhibitor, and hereditary angioedema treatment. English-language articles were searched from 1966 to the present to look for studies demonstrating the efficacy and the safety of C1-INH concentrate.Results: The English-language literature search revealed several studies showing significantly improved relief of HAE symptoms with the administration of C1-INH concentrate – many studies demonstrated some improvement of symptoms within 30 minutes. Side effects have been similar to placebo, and no proven cases of viral transmission have occurred in over 20 years.Conclusion: C1-INH concentrate appears to be a very safe and effective treatment option for HAE.Keywords: hereditary angioedema, c1 inhibitor, c1 esterase inhibitor, hereditary angioedema treatment

  13. Depressed activation of the lectin pathway of complement in hereditary angioedema

    DEFF Research Database (Denmark)

    Varga, L; Széplaki, G; Laki, J; Kocsis, A; Kristóf, K; Gál, P; Bajtay, Z; Wieslander, J; Daha, M R; Garred, P; Madsen, H O; Füst, G; Farkas, H

    2008-01-01

    ) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured by...

  14. Presence of C1-Inhibitor Polymers in a Subset of Patients Suffering from Hereditary Angioedema

    DEFF Research Database (Denmark)

    Elenius Madsen, Daniel; Hansen, Søren; Gram, Jørgen Brodersen; Bygum, Anette; Drouet, Christian; Sidelmann, Johannes Jakobsen

    2014-01-01

    Hereditary angioedema (HAE) is a potentially life-threatening disease caused by mutations in the gene encoding the serine protease inhibitor (serpin) C1 inhibitor (C1-inh). The mutations cause decreased functional plasma levels of C1-inh, which triggers unpredictable recurrent edema attacks...

  15. Management of acute attacks of hereditary angioedema: potential role of icatibant

    Directory of Open Access Journals (Sweden)

    Hilary J Longhurst

    2010-09-01

    Full Text Available Hilary J LonghurstDepartment of Immunology, Barts and The London NHS Trust, London, UKAbstract: Icatibant (Firazyr® is a novel subcutaneous treatment recently licensed in the European Union for acute hereditary angioedema. Hereditary angioedema, resulting from inherited partial C1 inhibitor deficiency, is a disabling condition characterized by intermittent episodes of bradykinin-mediated angioedema. Icatibant blocks bradykinin B2 receptors, attenutating the episode. Randomized double-blind, placebo-controlled trials of icatibant, showed significant superiority over oral tranexamic acid in 74 European patients and a trend to improvement in a similar US trial comparing icatibant with placebo in 55 patients. Outcomes for several endpoints did not reach significance in the US trial, perhaps because of low participant numbers and confounding factors: a further trial is planned. Open label studies have shown benefit in multiple treatments for attacks at all sites. Approximately 10% of patients require a second dose for re-emergent symptoms, usually 10 to 27 hours after the initial treatment. Its subcutaneous route of administration, good tolerability and novel mode of action make icatibant a promising addition to the limited repertoire of treatments for hereditary angioedema.Keywords: hereditary angioedema, bradykinin, icatibant, C1 inhibitor deficiency

  16. Urticaria and Prodromal Symptoms Including Erythema Marginatum in Danish Patients with Hereditary Angioedema

    DEFF Research Database (Denmark)

    Rasmussen, Eva R; Valente de Freitas, Priscila; Bygum, Anette

    2015-01-01

    Erythema marginatum is a characteristic skin rash seen in patients with hereditary angioedema (HAE); however, it can be confused with urticaria, leading to delay in correct diagnosis. The aim of this study was to clarify how often erythema marginatum is misinterpreted as urticaria, potentially...

  17. Rhucin, a recombinant C1 inhibitor for the treatment of hereditary angioedema and cerebral ischemia.

    Science.gov (United States)

    Longhurst, Hilary

    2008-03-01

    Pharming NV and Esteve are developing Rhucin, a recombinant human C1 esterase inhibitor. Rhucin is currently undergoing phase III clinical trials in North America and is awaiting regulatory approval in Western Europe for the treatment of prophylactic and acute hereditary angioedema. Pharming is also investigating Rhucin for the potential treatment of cerebral ischemic injury. PMID:18311668

  18. Hereditary persistence of alpha-fetoprotein (HPAFP) : review of the literature

    NARCIS (Netherlands)

    Houwert, A. C.; Giltay, J. C.; Lentjes, E. G. W. M.; Lock, M. T. W. T.

    2010-01-01

    Alpha-fetoprotein (AFP) serum levels are raised in several clinical conditions, ranging from non-pathological conditions to malignancies. Hereditary persistence of alpha-fetoprotein (HPAFP) is a rare benign disorder with elevated AFP levels. HPAFP is described as a benign autosomal dominantly inheri

  19. Orofacial hereditary haemorrhagic telangiectasia: high power diode laser in early and advanced lesion treatment

    Science.gov (United States)

    Tempesta, Angela; Franco, Simonetta; Miccoli, Simona; Suppressa, Patrizia; De Falco, Vincenzo; Crincoli, Vito; Lacaita, Mariagrazia; Giuliani, Michele; Favia, Gianfranco

    2014-01-01

    Hereditary Haemorrhagic Telangiectasia (HHT) is a muco-cutaneous inherited disease. Symptoms are epistaxis, visceral arterio-venous malformations, multiple muco-cutaneous telangiectasia with the risk of number increasing enlargement, bleeding, and super-infection. The aim of this work is to show the dual Diode Laser efficacy in preventive treatment of Early Lesions (EL telangiectasia.

  20. Allelic Dropout in the ENG Gene, Affecting the Results of Genetic Testing in Hereditary Hemorrhagic Telangiectasia

    DEFF Research Database (Denmark)

    Tørring, Pernille M; Kjeldsen, A.D.; Ousager, L.B.;

    2012-01-01

    Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder with three disease-causing genes identified to date: ENG, ACVRL1, and SMAD4. We report an HHT patient with allelic dropout that on routine sequence analysis for a known mutation in the family (c.817...

  1. Treatment of Laryngeal Telangiectatic Lesions in a Patient Diagnosed with Hereditary Haemorrhagic Telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, Anette Drøhse; Printz, Trine; Slot Mehlum, Camilla;

    2015-01-01

    Abstract We here present a case concerning a 69 year old female patient with Hereditary Haemorrhagic Telangiectasia (HHT). She was suffering from hoarseness due to a telangiectatic lesion on the right vocal cord. The lesion was treated with laser and the voice improved markedly, which is documented...

  2. Splenic arteriovenous malformation manifested by thrombocytopenia in hereditary hemorrhagic telangiectasia: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hee Jin; Choi, Jong Cheol; Oh, Jong Yeong; Cho, Jin Han; Kang, Myong Jin; Lee, Jin Hwa; Yoon, Seong Kuk; Nam, Kyeong Jin [College of Medicine, Dong-A University, Busan (Korea, Republic of)

    2008-09-15

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterized by epistaxis, telangiectases and visceral arteriovenous malformations (AVMs). The involvement of the gastrointestinal tract, liver, lung and cerebrum for HHT has been described, whereas little is known about AVMs of the spleen. We report here the radiological findings of a case of a splenic AVM manifested by thrombocytopenia in HHT.

  3. Abnormal red cell features associated with hereditary neurodegenerative disorders: the neuroacanthocytosis syndromes

    NARCIS (Netherlands)

    Franceschi, L. De; Bosman, G.J.C.G.M.; Mohandas, N.

    2014-01-01

    PURPOSE OF REVIEW: This review discusses the mechanisms involved in the generation of thorny red blood cells (RBCs), known as acanthocytes, in patients with neuroacanthocytosis, a heterogenous group of neurodegenerative hereditary disorders that include chorea-acanthocytosis (ChAc) and McLeod syndro

  4. Pancreatic pseudoaneurysm in a child with hereditary pancreatitis: diagnosis with multidetector CT angiography

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Hossam K.; Hagspiel, Klaus D.; Angle, John F.; Leung, Daniel A.; Spinosa, David J.; Matsumoto, Alan H. [Department of Radiology, University of Virginia Health System, Box 800170, VA 22908, Charlottesville (United States); McGahren, Eugene D.; Rodgers, Bradley M. [Department of Surgery, Division of Pediatric Surgery, University of Virginia Health System, Box 800170, VA 22908, Charlottesville (United States)

    2004-08-01

    Pseudoaneurysm formation is a serious vascular complication of pancreatitis. It most commonly affects splenic and gastroduodenal arteries. We report a rare case of superior mesenteric artery pseudoaneurysm in a child with hereditary pancreatitis. Multidetector CT angiography allowed the comprehensive assessment of the aneurysm and allowed accurate surgical planning obviating the need for catheter angiography. (orig.)

  5. Hereditary haemochromatosis: a case of iron accumulation in the basal ganglia associated with a parkinsonian syndrome

    DEFF Research Database (Denmark)

    Nielsen, J.E.; Jensen, L.N.; Krabbe, K

    1995-01-01

    patient is reported with hereditary haemochromatosis and a syndrome of dementia, dysarthria, a slowly progressive gait disturbance, imbalance, muscle weakness, rigidity, bradykinesia, tremor, ataxia, and dyssynergia. The findings on MRI of a large signal decrease in the basal ganglia, consistent with...

  6. Unravelling the genetic basis of hereditary disorders by high-throughput exome sequencing strategies

    NARCIS (Netherlands)

    Jazayeri, Omid

    2016-01-01

    The research presented in this thesis focuses on using Whole Exome Sequencing (WES) to unravel the genetic basis of human hereditary disorders with different inheritance patterns. We set out to apply WES as a diagnostic approach for establishing a molecular diagnosis in a highly heterogeneous group

  7. Hereditary angioderma: an uncommon cause of acute abdomen. Abdominal computed tomography and ultrasound findings

    International Nuclear Information System (INIS)

    We present an uncommon case of acute abdomen in a patient with hereditary angioderma. The ultrasound and CT findings described may suggest this diagnosis, thus avoiding useless surgical interventions in patients in whom the disease has not been previously diagnosed. (Author) 19 refs

  8. Pancreatic pseudoaneurysm in a child with hereditary pancreatitis: diagnosis with multidetector CT angiography

    International Nuclear Information System (INIS)

    Pseudoaneurysm formation is a serious vascular complication of pancreatitis. It most commonly affects splenic and gastroduodenal arteries. We report a rare case of superior mesenteric artery pseudoaneurysm in a child with hereditary pancreatitis. Multidetector CT angiography allowed the comprehensive assessment of the aneurysm and allowed accurate surgical planning obviating the need for catheter angiography. (orig.)

  9. Population screening for hereditary and familial cancer syndromes in Valka district of Latvia

    Directory of Open Access Journals (Sweden)

    Vanags Andrejs

    2010-10-01

    Full Text Available Abstract Background The growing possibilities of cancer prevention and treatment as well as the increasing knowledge about hereditary cancers require proper identification of the persons at risk. The aim of this study was to test the outcome of population screening in the scientific and practical evaluation of hereditary cancer. Methods Population screening for hereditary cancer was carried out retrospectively in a geographic area of Latvia. Family cancer histories were collected from 18642 adults representing 76.6% of the population of this area. Hereditary cancer syndromes were diagnosed clinically. Molecular testing for BRCA1 founder mutations 300 T/G, 4153delA and 5382insC was conducted in 588 persons who reported at least one case of breast or ovary cancer among blood relatives. Results Clinically, 74 (0.40%; 95% confidence interval (CI: 0.32 - 0.50% high-risk and 548 (2.94%, 95% CI: 2.71 - 3.19 moderate-risk hereditary cancer syndromes were detected covering wide cancer spectrum. All syndromes were characterised by high cancer frequency among blood relatives ranging 8.6 - 46.2% in contrast to spouse correlation of 2.5 - 3.6%. The mean age of cancer onset ranged 38.0 - 72.0 years in different syndromes. The BRCA1 gene mutations were identified in 10 (1.7%; 95% CI: 0.9 - 3.1% probands. Families with established BRCA1 gene founder mutations were identified with the frequency 1:2663 clinically screened persons. Conclusions Population screening is a useful practical tool for the identification of persons belonging to families with high frequency of malignant tumours. The whole hereditary and familial cancer spectrum along with the age structure was identified adjusting follow-up guidelines. Another benefit of the population screening is the possibility to identify oncologically healthy persons belonging to hereditary and familial cancer families so that appropriate surveillance can be offered. Clinical diagnostics is appropriate for population

  10. Hereditary Connective Tissue Disorders: a Modern Approach to Classification and Diagnosis (Review

    Directory of Open Access Journals (Sweden)

    Klemenov А.V.

    2014-06-01

    Full Text Available Hereditary connective tissue disorders — a genetically and clinically heterogeneous group of diseases united by common congenital mesenchymal abnormalities — is one of the most debatable problems of clinical medicine. A great while, from the whole variety of hereditary connective tissue disorders, only “differentiated” (with concerted diagnostic recommendations, monogenic syndromes registered in OMIM, have been the focus of attention of medical community. However, numerous unclassifiable forms with multi-factorial development mechanisms or so called dysplastic phenotypes have not been taken into account when estimating the disease prognosis and determining treatment policy. The review represents the current concepts of the nomenclature of hereditary connective tissue disorders, and considers the diagnostic criteria of the classified monogenic syndromes (Marfan syndrome and Ehlers–Danlos syndrome, MASS-phenotype, primary mitral valve prolapse, joint hypermobility syndrome and unclassifiable dysplastic phenotypes (МASS-like phenotypes, marfanoid appearance, Ehlers-like phenotype, benign joint hypermobility, unclassifiable phenotype in the view of recent international and domestic recommendations. Congenital mesenchymal disorders have been represented in the form of a continuous list in order of decreasing clinical intensity of their manifestations and prognostic value reduction (“phenotypic continuum”: from monogenic syndromes through dysplastic phenotypes to unclassifiable phenotypes. The authors have laid emphasis on the difficulties of clinical identification of hereditary connective tissue disorders related to non-specificity of external and visceral markers of connective tissue weakness and certain conventionality of diagnostic criteria. The review has shown the debating aspects of diagnosis and interpretation of clinical significance of some hereditary connective tissue disorders.

  11. Studies on bone scintigraphy in renal osteodystrophy

    International Nuclear Information System (INIS)

    Bone scintigraphy was superior over roentgenography for detection of abnormal bone findings in chronic dialysis patients. According to the type of scintigraphic findings, an increase in the hot area in the cranium or the mandibule seemed to express fibrous osteitis due to secondary hyperparathyroidism. Multiple coin-shaped hot areas in ribs were thought to indicate advanced osteomalacia or osteomalacia in patients with aluminum poisoning. The 4 hr-B/St ratio of the cranium was thought to serve as a quantitative indicator of the status of fibrous osteitis due to secondary hyperparathyroidism to show the progress and therapeutic course of the disease. (Chiba, N.)

  12. Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study

    DEFF Research Database (Denmark)

    Park, Jae-Gahb; Kim, Duck-Woo; Hong, Chang Won;

    2006-01-01

    PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members of the Internatio.......8%, P < 0.001). CONCLUSIONS: In HNPCC patients, SBC can be the first and only cancer and may develop as soon as the early teens. The distribution of MSH2 mutations found in patients with HNPCC-associated SBCs significantly differed from that found in the control group (P < 0.001)....

  13. MLH1 promoter germline-methylation in selected probands of Chinese hereditary non-polyposis colorectal cancer families

    OpenAIRE

    Zhou, Heng-Hua; Yan, Shi-Yan; Zhou, Xiao-Yan; Du, Xiang; Zhang, Tai-Ming; Cai, Xu; Lu, Yong-Ming; Cai, San-Jun; Shi, Da-Ren

    2008-01-01

    AIM: To detect the MLH1 gene promoter germline-methylation in probands of Chinese hereditary nonpolyposis colorectal cancer (HNPCC), and to evaluate the role of methylation in MLH1 gene promoter and molecular genetics in screening for HNPCC.

  14. Absence of close linkage between benign hereditary chorea and the locus D4S10 (probe G8).

    OpenAIRE

    Quarrell, O W; Youngman, S; Sarfarazi, M; P.S. Harper

    1988-01-01

    A genetic linkage study between benign hereditary chorea and the locus D4S10 using the DNA probe G8 has shown two recombinations in five small families. There were negative lod scores at recombination fractions that show conclusive evidence of linkage in 16 larger British Huntington's disease families. We suggest that although benign hereditary chorea and Huntington's disease may have some clinical similarities they are probably at two different loci.

  15. Natural History and Outcome of Hepatic Vascular Malformations in a Large Cohort of Patients with Hereditary Hemorrhagic Teleangiectasia

    OpenAIRE

    Buscarini, Elisabetta; Leandro, Gioacchino; Conte, Dario; DANESINO, CESARE; Daina, Erica; Manfredi, Guido; Lupinacci, Guido; Brambilla, Gianfranco; Menozzi, Fernanda; De Grazia, Federico; Gazzaniga, Pietro; INAMA, GIUSEPPE; Bonardi, Roberto; Blotta, Pasquale; Forner, PierAngelo

    2011-01-01

    Background Hereditary hemorrhagic telangiectasia is a genetic disease characterized by teleangiectasias involving virtually every organ. There are limited data in the literature regarding the natural history of liver vascular malformations in hemorrhagic telangiectasia and their associated morbidity and mortality. Aim This prospective cohort study sought to assess the outcome of liver involvement in hereditary hemorrhagic telangiectasia patients. Methods We analyzed 16 years of surveillance d...

  16. Hereditary hemorrhagic telangiectasia: a rare cause of long-lasting abdominal distension in an 8-year-old boy

    Institute of Scientific and Technical Information of China (English)

    陈雷铃; 郎诗明; 胡廷泽; 钟麟; 李俊杰

    2002-01-01

    @@ Abdominal distension is a common complaint encountered in pediatric surgery. In most cases, Hirschsprung's disease is the most common cause associated with abdominal distension in older children. Hereditary hemorrhagic telangiectasia is a rare disease which commonly presents with hemorrhage and anemia. We treated an 8-year-old boy with long lasting intractable abdominal distension associated with hereditary hemorrhagic telangiectasia. Clinicopathologic features of this rare entity are discussed with emphasis on its pathogenesis and diagnosis.

  17. Hepatocellular carcinoma associated with hereditary hemochromatosis occurring in non-cirrhotic liver.

    Science.gov (United States)

    von Delius, S; Lersch, C; Schulte-Frohlinde, E; Fend, F; Dobritz, M; Schmid, R M; Eckel, F

    2006-01-01

    The occurrence of primary hepatocellular carcinoma (HCC) in patients with hereditary hemochromatosis (HH) is well known. Thereby, the development of liver cirrhosis seems to be a prerequisite. Whether or not a hepatic iron overload in the context of hereditary hemochromatosis is an independent risk factor for HCC remains unclear. To date there are only a few reports about HCC arising in non-cirrhotic livers in the presence of HH. We report the case of a 64-year-old man who presented to our outpatient clinic with HCC. Liver cirrhosis could be excluded. Detailed exploration of the patient's history revealed that he had been treated by venesection for about 10 years up to 15 years ago. Subsequent investigations showed an elevated serum ferritin and transferrin saturation. The diagnosis of HH was confirmed by genetic testing, with homozygosity for the Cys282Tyr mutation. The patient received palliative chemotherapy and finally died 15 months after initial diagnosis of HCC. PMID:16397838

  18. The Prevention of Hereditary Breast and Ovarian Cancer: A Personal View

    Directory of Open Access Journals (Sweden)

    Narod Steven

    2004-02-01

    Full Text Available Abstract Options for the prevention of hereditary breast and ovarian cancer include screening, preventive surgery and chemoprevention. Screening studies with magnetic resonance imaging of the breast are promising but the technology is not widespread and MRI is unlikely to be available as a screening tool in the near future. Prophylactic oophorectomy and mastectomy are effective preventive measures and are gaining in acceptance by patients and physicians. Preventive mastectomy is effective against both primary and contralateral breast cancer. Oophorectomy prevents ovarian cancer, and if done prior to menopause, will prevent breast cancer as well. Tamoxifen has been shown to prevent contralateral breast cancers in BRCA1 and BRCA2 carriers but is not widely accepted as a means of primary prevention. Oral contraceptives and tubal ligation will reduce the risk of hereditary ovarian cancer and should be considered in women who wish to retain ovarian function.

  19. Bilateral cloudy cornea: is the usual suspect congenital hereditary endothelial dystrophy or stromal dystrophy?

    Science.gov (United States)

    Acar, Banu Torun; Bozkurt, Kansu Tahir; Duman, Erkan; Acar, Suphi

    2016-01-01

    We provide the diagnosis, treatment and follow-up period of a patient with cloudy cornea in both eyes from birth. A 4-year-old girl presented with blurring in both eyes. Penetrating keratoplasty (PK) was performed with the preliminary diagnosis of congenital hereditary endothelial dystrophy in June 2012. According to the pathology report for extracted host tissue, the Descemet's membrane (DM) and endothelium were healthy and diagnosis was reported to be congenital hereditary stromal dystrophy. Deep anterior lamellar keratoplasty was performed on the left eye. The DM was transparent at follow-up. Cornea transplantation is the only choice to provide visual rehabilitation in children with congenital cloudy cornea. However, it is known that the prognosis of traditional PK in the paediatric age group is not good. Therefore, when using alternative keratoplasty (deep anterior lamellar keratoplasty, Descemet's stripping automated endothelial keratoplasty) options, pathological examination of the host tissue should be made. PMID:27107055

  20. Targeted therapy for hereditary cancer syndromes: neurofibromatosis type 1, neurofibromatosis type 2, and Gorlin syndrome.

    Science.gov (United States)

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Hereditary cancer syndromes are well known in the oncology community, typically affecting children, adolescents, and young adults and thereby resulting in great cumulative morbidity and mortality. These syndromes often lag behind their de novo counterparts in the development of approved novel treatment options due to their rarity in the general population. Recent work has allowed the identification of molecular aberrations and associated targeted therapies that may effectively treat these conditions. In this review, we seek to characterize some of the involved aberrations and associated targeted therapies for several germline malignancies, including neurofibromatosis types 1 and 2, and Gorlin syndrome. Though patients with hereditary cancer syndromes may be too rare to effectively include in large clinical trials, by understanding the pathophysiology of these diseases, clinicians can attain insights into the use of targeted therapies in their own practice when treating affected individuals. PMID:25549703

  1. Hereditary/familial versus sporadic prostate cancer: few indisputable genetic differences and many similar clinicopathological features.

    Science.gov (United States)

    Alberti, C

    2010-01-01

    Genetic factors and their interactions with environmental conditions and internal microenvironment influence the prostate cancer (PC) development, so that gene expression couldn't strictly occur on the basis of reductionist determinisms of DNA causality but should also conform to multifactorial and stochastic events, moreover, considering the pre-RNA alternative splicing-mediated multi-protein assemblying mechanisms. Nevertheless, after age and ethnic background, the strongest epidemiological risk factor for PC is a positive family history. However, apart from RNaseL-, ElaC2-, MSR1-genes, there are not other identified high-risk genetic variants which might be considered responsible for hereditary PC, moreover suggesting that familial PC is a genetically heterogeneous disease, many gene loci rather than a specific major susceptibility gene predisposing to it. Gene-environment interactions play a crucial role in cancer development especially when low penetrance genes, such as in case of genetic polymorphisms, are the major players. Several epidemiological studies show, in some families, a possible, either syncronous or metachronous, association of other tumors (breast, brain, gastrointestinal tumors, lymphomas) with PC, thus suggesting a common genetic background. As far as the role of androgen metabolism and androgen receptor (AR)-related genes in the development of familial PC is concerned, a small number of either guanine-guanine-cytosine (risk. Regarding the expression of both androgen and estrogen receptor-related genes in sporadic and hereditary PC, the immunohistochemistry findings show that the percentage of AR-positive cancer cells is higher in hereditary PC than in sporadic forms, whereas the mean number of estrogen-alpha-receptor-positive stromal cells is higher in sporadic PC rather than in that hereditary. As for 5-alpha-steroid-reductase-2 gene, the dinucleotide thymine-adenine repeated 18 times on the last exon, confers an increased PC predisposition

  2. Hereditary angioedema type III (estrogen-dependent) report of three cases and literature review.

    Science.gov (United States)

    Miranda, Amanda Rodrigues; Ue, Ana Paula Fusel de; Sabbag, Dominique Vilarinho; Furlani, Wellington de Jesus; Souza, Patrícia Karla de; Rotta, Osmar

    2013-01-01

    In this article, three cases of hereditary angioedema (HAE) type III (estrogen-dependent or with normal C1 inhibitor) are reported. The HAE was initially described in women of the same family in association with high-leveled estrogenic conditions such as the use of oral contraceptives and pregnancy. There is no change in the C1 inhibitor as happens in other types of hereditary angioedema, and mutations are observed in the encoding gene of the XII factor of coagulation in several patients. The current diagnosis is mainly clinical and treatment consists in the suspension of the triggering factors and control of acute symptoms. A brief review of physiopathology, clinical features, genetic alterations and treatment are also presented. PMID:24068129

  3. Treatment of type I and II hereditary angioedema with Rhucin, a recombinant human C1 inhibitor.

    Science.gov (United States)

    Varga, Lilian; Farkas, Henriette

    2008-11-01

    Hereditary and acquired angioedema are of outstanding clinical importance, as edematous attacks associated with these conditions can thrust afflicted patients into mortal danger. Currently, C1 inhibitor concentrate - a human blood product - is available as a replacement therapy. In view of the limited number of donors, as well as the risk of transmission of blood-borne infections, it is a reasonable expectation to develop a therapeutic alternative based on recombinant technology, which would eliminate all these shortcomings. Pharming (Leiden, The Netherlands) has developed Rhucin, a recombinant human C1 inhibitor, as a proprietary product, which is currently being evaluated in Phase III clinical trials. Ongoing studies conducted within the framework of the development program are almost complete and their interim findings are reassuring. This should facilitate successful regulatory approval in the near future, which is indispensable in order to make Rhucin available for patients with hereditary angioedema or other disorders amenable to C1 inhibitor replacement. PMID:20477114

  4. Induced pluripotent stem cells:Landscape for studying and treating hereditary hearing loss

    Institute of Scientific and Technical Information of China (English)

    Tao Peng; Yunpeng Dong; Ganghua Zhu; Dinghua Xie

    2014-01-01

    Hearing loss (HL) is one of the most widespread sensory disorders, affecting approximately 1 in 500 newborns. Heritable diseases of the inner ear are the leading causes of prelingual HL. Treating of hereditary HL and understanding its underlying mechanisms remain difficult challenges to otolaryngologists. As stem cells are capable of self-renewal and differentiation, they are ideally suited both for disease modeling and regenerative medicine. Recently, description of induced pluripotent stem cells (iPSCs) has allowed the field of disease modeling and personalized therapy to become far more accessible and physiologically relevant, as iPSCs can be generated from patients of any genetic background. This review briefly describes the advantages of iPSCs technology and discusses potential applications of this powerful biological tool in studying and treating hereditary HL.

  5. Genetic linkage analysis of hereditary arthro-ophthalmopathy (Stickler syndrome) and the type II procollagen gene.

    OpenAIRE

    Knowlton, R G; Weaver, E. J.; Struyk, A F; Knobloch, W H; King, R A; Norris, K; Shamban, A; Uitto, J; Jimenez, S A; Prockop, D J

    1989-01-01

    Hereditary arthro-ophthalmopathy (AO), or Stickler syndrome, is a dominantly inherited disorder characterized by vitreo-retinal degeneration and frequently accompanied by epiphyseal dysplasia and premature degenerative joint disease. Three large families with AO were analyzed for clinical manifestations of the disease and for coinheritance of the genetic defect with RFLPs in the type II procollagen gene (COL2A1). Genetic linkage between AO and COL2A1 was demonstrated in the largest family, wi...

  6. Diagnosis and screening of patients with hereditary angioedema in primary care

    OpenAIRE

    Henao, Maria Paula

    2016-01-01

    Maria Paula Henao,1 Jennifer L Kraschnewski,1 Theodore Kelbel,2 Timothy J Craig3 1Department of Medicine, 2Division of Allergy and Immunology, 3Department of Medicine and Pediatrics, Pennsylvania State University College of Medicine at Hershey Medical Center, Hershey, PA, USA Abstract: Hereditary angioedema (HAE) is a rare autosomal dominant disease that commonly manifests with episodes of cutaneous or submucosal angioedema and intense abdominal pain. The condition usually presents due to a...

  7. Diagnosis and screening of patients with hereditary angioedema in primary care

    OpenAIRE

    Henao, Maria Paula; Kraschnewski, Jennifer L.; Kelbel, Theodore; Craig, Timothy J.

    2016-01-01

    Hereditary angioedema (HAE) is a rare autosomal dominant disease that commonly manifests with episodes of cutaneous or submucosal angioedema and intense abdominal pain. The condition usually presents due to a deficiency of C1 esterase inhibitor (C1-INH) that leads to the overproduction of bradykinin, causing an abrupt increase in vascular permeability. A less-understood and less-common form of the disease presents with normal C1-INH levels. Symptoms of angioedema may be confused initially wit...

  8. The Effects of a Genetic Counseling Educational Program on Hereditary Breast Cancer for Korean Healthcare Providers

    OpenAIRE

    Lee, Jihyoun; Cho, Hyung Jung; Yoo, Han-Wook; Park, Sue K.; Yang, Jae Jeong; Kim, Sung-Won; Kang, Eunyoung; Ahn, Sei-Hyun; Lee, Soo-Jung; Suh, Young Jin; Kim, Sung Yong; Kim, Eun-Kyu; Moon, Nan Mo; Lee, Min Hyuk; ,

    2013-01-01

    Purpose Systematic educational programs and genetic counseling certification courses for hereditary breast/ovarian cancer (HBOC) have not yet been introduced in Korea. We provided and evaluated the effects of genetic counseling education on Korean healthcare providers' knowledge, awareness, and counseling skills for patients at high risk of HBOC. Methods A 3-day educational program was conducted for healthcare providers who were interested in genetic counseling for patients at high risk of HB...

  9. African American Women’s Limited Knowledge and Experiences with Genetic Counseling for Hereditary Breast Cancer

    OpenAIRE

    Sheppard, Vanessa B.; Graves, Kristi D.; Christopher, Juleen; Hurtado-de-Mendoza, Alejandra; Talley, Costellia; Williams, Karen Patricia

    2013-01-01

    Genetic counseling and testing for hereditary breast cancer have the potential benefit of early detection and early interventions in African American women. However, African American women have low use of these services compared to White women. We conducted two focus groups with African American women diagnosed with breast cancer (affected group, n=13) and women with at least one first-degree relative with breast/ovarian cancer (unaffected group, n= 8). A content analysis approach was employe...

  10. Women’s Satisfaction with Genetic Counseling for Hereditary Breast-Ovarian Cancer: Psychological Aspects

    OpenAIRE

    Tercyak, Kenneth P.; DeMarco, Tiffani A.; Mars, Bryn D.; Peshkin, Beth N.

    2004-01-01

    Women who participate in BRCA1/2 cancer genetic counseling do so for a variety of reasons, including learning quantitative risk information about their chances of developing hereditary breast-ovarian cancer at some point during their lifetimes. For these women, obtaining pre-test and disclosure genetic counseling with a professional affords them numerous potential benefits, including adequate preparation for, and accurate interpretation of, their test results. In consequence, women commonly r...

  11. Hip dysplasia associated with a hereditary sensorimotor polyneuropathy mimics a myopathic process

    OpenAIRE

    Mohammad Javad Hadianfard; Alireza Ashraf

    2012-01-01

    Some orthopedic complications have been reported in the hereditary neuropathies. However, the association of the hip dysplasia with this category of neuropathy is rarely recognized. We present a 13-year-old boy with the progressive weakness of the lower extremities, difficulty in walking, climbing stairs, and rising from floor; a wide-based, hyper-extended and waddling gait similar to a myopathic process. Hip radiography showed dysplastic acetabulae with hip subluxation, broken Shenton′s line...

  12. Hereditary spastic paraplegia-causing mutations in atlastin-1 interfere with BMPRII trafficking

    OpenAIRE

    Zhao, Jiali; Hedera, Peter

    2012-01-01

    Disruption of the bone morphogenic protein (BMP)-linked signaling pathway has been suggested as an important factor in the development of hereditary spastic paraplegia (HSP). HSP-causing proteins spastin, spartin and NIPA1 were reported to inhibit the BMP pathway. We have previously shown a strong interaction of NIPA1 and atlastin-1 proteins. Hence, we investigated the role of another HSP-associated protein atlastin-1 in this signaling cascade. Endogenous and expressed atlastin-1 showed a str...

  13. Hereditary Hemorrhagic Telangiectasia Presenting as High Output Cardiac Failure during Pregnancy

    OpenAIRE

    Tareq Goussous; Alex Haynes; Katherine Najarian; Marcos Daccarett; Shukri David

    2009-01-01

    High-output cardiac failure secondary to hepatic involvement is a rare complication of hereditary hemorrhagic telangiectasia (HHT). Here we report a 43-year-old woman who presented at 29 weeks gestation of her second pregnancy with complications of right-sided heart failure and preterm labor. After delivery via cesarean section, the patient was found to have intrahepatic arteriovenous malformations through non-invasive imaging. Subsequently, a family history of vascular malformations and epis...

  14. Effect of intrathecal baclofen on gait control in human hereditary spastic paraparesis.

    OpenAIRE

    Dan, Bernard; Bouillot, Ethel; Bengoetxea, Ana; Chéron, Guy

    2000-01-01

    The covariation between thigh, shank and foot elevation angles during locomotion was analysed by means of orthogonal planar regression in a patient with pure hereditary spastic paraparesis before and after an intrathecal bolus of baclofen and in seven healthy subjects. The size, shape and spatial orientation of the loop defining patient's planar covariation (thigh angle vs. shank angle vs. foot angle) significantly differed from the controls' before baclofen, whereas these features resumed no...

  15. A unique case of hereditary bilateral segmental neurofibromatosis on the face.

    Science.gov (United States)

    Jankovic, Irena; Kovacevic, Predrag; Visnjic, Milan; Jankovic, Dimitrije; Velickovic, Milena

    2012-01-01

    Segmental neurofibromatosis is a rare clinical finding generally with no family history and facial involvement. There are four subtypes of segmental neurofibromatosis: true segmental, localized cases with deep involvement, hereditary segmental and bilateral segmental neurofibromatosis. Here we report three patients from the same family (father, son and granddaughter) with segmental bilateral neurofibromatosis on the face. This form has not been noticed in the literature. PMID:23197210

  16. Molecular Diagnosis of Hereditary Fructose Intolerance: Founder Mutation in a Community from India

    OpenAIRE

    Bijarnia-Mahay, Sunita; Movva, Sireesha; Gupta, Neerja; Sharma, Deepak; Puri, Ratna D.; Kotecha, Udhaya; Saxena, Renu; Kabra, Madhulika; Mohan, Neelam; Verma, Ishwar C.

    2015-01-01

    Hereditary fructose intolerance (HFI) is a difficult-to-confirm diagnosis, requiring either invasive liver biopsy-enzyme assay or potentially hazardous fructose challenge test or expensive molecular genetic analysis. Therefore, worldwide there has been a trend towards finding “common mutations” in distinct ethnic groups to simplify the process of diagnosis. The nonspecific presentation of the disease often leads to diagnostic confusion with other metabolic liver disorders such as glycogenoses...

  17. Hereditary combined deficiency of the vitamin K-dependent clotting factors

    OpenAIRE

    Mariani Guglielmo; Napolitano Mariasanta; Lapecorella Mario

    2010-01-01

    Abstract Hereditary combined vitamin K-dependent clotting factors deficiency (VKCFD) is a rare congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X as well as natural anticoagulants protein C, protein S and protein Z. The spectrum of bleeding symptoms ranges from mild to severe with onset in the neonatal period in severe cases. The bleeding symptoms are often life-threatening, occur both spontaneously and in a surgical setting, and usu...

  18. Distinctions in sensitivity and repair of cells of children with some hereditary diseases

    Energy Technology Data Exchange (ETDEWEB)

    Zasukhina, G.D.; Barashnev, Yu.I.; Vasil' eva, I.M.; Sdirkova, N.I.; Semyachkina, A.N. (AN SSSR, Moscow. Inst. Obshchej Genetiki)

    A study was made of blood cell sensitivity of children with some hereditary diseases, to ..gamma..-radiation and 4-nitro-quinoline-1-oxide. Using the host cell reactivation and chromatographic methods we revealed the increase in the sensitivity to the above mentioned agents and inhibition of the repair function in cells of patients with the following diseases: Marfan's disease, histidinemia, osteogenesis imperfecta, Sylvere-Russelle, Laurence, Franchescetti, and Losch-Nychane syndromes.

  19. Distinctions in sensitivity and repair of cells of children with some hereditary diseases

    International Nuclear Information System (INIS)

    A study was made of blood cell sensitivity of children, with some hereditary diseases, to ν-radiation and 4-nitro-quinoline-1-oxide. Using the host cell reactivation and chromatographic methods we revealed the increase in the sensitivity to the above mentioned agents and inhibition of the repair function in cells of patients with the following diseases: Marfan's disease, histidinemia, osteogenesis imperfecta, Sylvere-Russelle, Laurence, Franchescetti, and Losch-Nychane syndromes

  20. [Hereditary epidermolysis bullosa in school children and adolescents : Clinical picture and interdisciplinary management].

    Science.gov (United States)

    Ott, H; Eich, C; Schriek, K; Ludwikowski, B

    2016-04-01

    Hereditary epidermolysis bullosa (EB) represents a clinically heterogeneous group of congenital blistering disorders requiring multiprofessional care. EB is associated with a broad spectrum of potentially severe complications often reaching their full extent during school age and adolescence. This review aims at summarizing cutaneous manifestations of EB as well as extracutaneous complications of this complex disease and their interdisciplinary management. PMID:26943360

  1. Hereditary susceptibility to inner ear stress agents studied in heterozygotes of the German waltzing guinea pig

    OpenAIRE

    Skjönsberg, Åsa

    2006-01-01

    The German waltzing guinea pig is a strain of animals expressing deafness and severe balance disorders already at birth. The mutation arose spontaneously in a breeding facility in Germany and as the affected animals show a characteristic waltzing behavior, the strain is named the German waltzing guinea pig. The strain is presently bred only at Karolinska Institutet. The hereditary inner car impairment has a recessive mode of inheritance and the strain thus produces not o...

  2. Assessment of fetal-maternal haemorrhage in mothers with hereditary persistence of fetal haemoglobin.

    OpenAIRE

    Patton, W N; Nicholson, G S; Sawers, A H; Franklin, I M; Ala, F A; Simpson, A W

    1990-01-01

    Kleihauer examination of peripheral blood cannot be used reliably to detect transplacental fetal-maternal haemorrhage in mothers with hereditary persistence of fetal haemoglobin (HPFH). In Rh(D) negative pregnancies diagnostic confusion with a large fetal-maternal haemorrhage could result in the administration of inappropriately excessive amounts of anti-D immunoglobulin, and the inability to diagnose and quantify transplacental haemorrhage in maternal HPFH by current methods could result in ...

  3. A hereditary disposition for bovine peripheral nerve sheath tumors in Danish Holstein cattle

    OpenAIRE

    Grossi, Anette B.; Agerholm, Jorgen S.; Christensen, Knud; Jensen, Henrik E; Leifsson, Pall S.; Bendixen, Christian; Karlskov-Mortensen, Peter; Fredholm, Merete

    2014-01-01

    Background: Peripheral nerve sheath tumors (PNSTs) are frequently found in Danish cattle at slaughter. Bovine PNSTs share several gross and histopathological characteristics with the PNSTs in humans with heritable neurofibromatosis syndromes. The aim of the present study was to investigate a possible hereditary disposition to PNSTs in dairy cattle by statistical analysis performed on data from 567 cattle with PNSTs. Furthermore, a preliminary genome-wide association study (GWAS) was performed...

  4. Leber's hereditary optic neuropathy with late disease onset: clinical and molecular characteristics of 20 patients

    OpenAIRE

    Dimitriadis, Konstantin; Leonhardt, Miriam; Yu-Wai-Man, Patrick; Kirkman, Matthew Anthony; Korsten, Alex; De Coo, Irenaeus F; Chinnery, Patrick Francis; Klopstock, Thomas

    2014-01-01

    Background: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. Here we describe the clinical and molecular characteristics of 20 patients with disease onset after the age of 50 years (late onset-LHON). Methods: From a cohort of 251 affected and 277 unaffected LHON carriers, we identified 20 patients with onset of visual loss after the age of 50 years. Using structured questionnaires, data including basic demographic de...

  5. Successful treatment of bleeding gastro-intestinal angiodysplasia in hereditary haemorrhagic telangiectasia with thalidomide

    OpenAIRE

    Alam, Mohamed Aftab; Sami, Sarmad; Babu, Sathish

    2011-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterised by epistaxis, cutaneous telangiectasia and visceral arterio-venous malformations (AVMs). It affects approximately one in 5000 people. Control of sustained and repeated haemorrhages from telangiectasias in the nose and gut in patients who may be transfusion dependent is clinically challenging. After repeated endoscopic coagulations, multiple lesions often recur at other sites of gastro-intestinal tract...

  6. Diagnosis, investigation and management of hereditary spastic paraplegias in the era of next-generation sequencing

    OpenAIRE

    Hensiek, Anke; Kirker, Stephen; Reid, Evan

    2014-01-01

    The hereditary spastic paraplegias (HSPs) are a group of genetic conditions in which spastic paralysis of the legs is the principal clinical feature. This is caused by a relatively selective distal axonal degeneration involving the longest axons of the corticospinal tracts. Consequently, these conditions provide an opportunity to identify genes, proteins and cellular pathways that are critical for axonal health. In this review, we will provide a brief overview of the classification, clinical ...

  7. The mitochondrial superoxide dismutase A16V polymorphism in the cardiomyopathy associated with hereditary haemochromatosis

    OpenAIRE

    Valenti, L; Conte, D; A. Piperno; P. Dongiovanni; Fracanzani, A.; Fraquelli, M; Vergani, A.; Gianni, C; Carmagnola, L; Fargion, S

    2004-01-01

    The A16V mitochondrial targeting sequence polymorphism influences the antioxidant activity of MnSOD, an enzyme involved in neutralising iron induced oxidative stress. Patients with hereditary haemochromatosis develop parenchymal iron overload, which may lead to cirrhosis, diabetes, hypogonadism, and heart disease. The objective of this study was to determine in patients with haemochromatosis whether the presence of the Val MnSOD allele, associated with reduced enzymatic activity, affects tiss...

  8. Hereditary transthyretin-related amyloidosis: clinical and physiopathologic profile and natural history

    OpenAIRE

    Gallelli, Ilaria

    2012-01-01

    Background. Hereditary transthyretin (TTR)-related amyloidosis (ATTR) is mainly considered a neurologic disease. We assessed the phenotypic and genotypic spectrum of ATTR in a non-endemic, Caucasian area and evaluated prevalence, genetic background and disease profile of cases with an exclusively cardiac phenotype, highlighting possible hints for the differential diagnosis with hypertrophic cardiomyopathy (HCM) and senile systemic amyloidosis (SSA) Methods and Results. In this Italian m...

  9. A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy

    OpenAIRE

    Haghighi, Kobra; Kolokathis, Fotis; Gramolini, Anthony O.; Waggoner, Jason R.; Pater, Luke; Lynch, Roy A.; Fan, Guo-Chang; Tsiapras, Dimitris; Parekh, Rohan R.; Dorn, Gerald W., II; MacLennan, David H.; Kremastinos, Dimitrios Th; Kranias, Evangelia G.

    2006-01-01

    The sarcoplasmic reticulum Ca2+-cycling proteins are key regulators of cardiac contractility, and alterations in sarcoplasmic reticulum Ca2+-cycling properties have been shown to be causal of familial cardiomyopathies. Through genetic screening of dilated cardiomyopathy patients, we identified a previously uncharacterized deletion of arginine 14 (PLN-R14Del) in the coding region of the phospholamban (PLN) gene in a large family with hereditary heart failure. No homozygous individuals were ide...

  10. Hereditary Angioedema: Report of Three Cases and Approach to Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    Sadiye Kuş

    2009-06-01

    Full Text Available Hereditary angioedema (HAE is a distinctive form of recurrent angioedema with life threatening consequences. Type I is defined with quantitative C1 esterase inhibitor (C1 INH deficiency, type II with functional C1 INH deficency and type III with normal quantity and function of C1 INH respectively. Here in, We present three cases with HAE and discuss diagnostic and therapeutic issues.

  11. Modified Descemet's Stripping Automated Endothelial Keratoplasty for Congenital Hereditary Endothelial Dystrophy

    OpenAIRE

    Mahmoodreza Panahi-Bazaz; Farideh Sharifipour; Mohammad Malekahmadi

    2014-01-01

    A 19-year-old male with congenital hereditary endothelial dystrophy (CHED) presented with severe bilateral corneal clouding precluding any view of the intraocular structures. He underwent modified Descemet′s stripping automated endothelial keratoplasty (DSAEK) technique including a suture pull-through technique to prevent lens damage. Surgery resulted in progressive clearing of the cornea and decreased corneal thickness. Visual acuity increased from hand motions preoperatively to counting fin...

  12. Hereditary Inclusion Body Myopathy: Single Patient Response to Intravenous Dosing of GNE Gene Lipoplex

    OpenAIRE

    Nemunaitis, Gregory; Jay, Chris M.; Maples, Phillip B; Gahl, William A; Huizing, Marjan; Yardeni, Tal; Tong, Alex W.; Phadke, Anagha P; Pappen, Beena O.; Bedell, Cynthia; Allen, Henry; Hernandez, Cathy; Templeton, Nancy S.; Kuhn, Joseph; Senzer, Neil

    2011-01-01

    Hereditary inclusion body myopathy (HIBM) is an autosomal recessive adult-onset myopathy due to mutations in the GNE (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase) gene. Affected patients have no therapeutic options. We have previously demonstrated in preclinical testing the ability to safely correct GNE gene function through liposomal delivery of the wild-type GNE gene. Results were verified in a single patient treated by intravenous infusion of GNE gene lipoplex. A single ...

  13. Incidence of hereditary amyloidosis and autoinflammatory diseases in Sweden: endemic and imported diseases

    OpenAIRE

    Hemminki, Kari; Li, Xinjun; Försti, Asta; Sundquist, Jan; Sundquist, Kristina

    2013-01-01

    Background: Amyloidoses are a heterogeneous group of progressive diseases caused by tissue deposition of misfolded proteins. According to the International Classification of Diseases, hereditary amyloidosis is divided into neuropathic and non-neuropathic forms. In Sweden, neuropathic heredofamilial amyloidosis has been identified as familial amyloidotic polyneuropathy (FAP), a fatal disease that is treated by liver transplantation. The non-neuropathic form includes familial autoinflammatory d...

  14. 99mTc-MAA Pulmonary Scintigraphy in Hereditary Hemorrhagic Telangiectasia.

    Science.gov (United States)

    Yang, Fang; Yuan, Leilei; Ma, Daqing; Yang, Jigang

    2016-08-01

    A 5-year-old boy was admitted due to shortness of breath. Blood gas analysis showed hypoxemia. However, thoracic and abdominal CT, brain MRI, and MR angiography were all normal. A Tc-MAA pulmonary scintigraphy revealed right-to-left shunting of the blood. Further genetic analysis showed the mutations in the activin receptor-like kinase 1 gene, and a diagnosis of hereditary hemorrhagic telangiectasia was made. PMID:27163461

  15. Massive Pulmonary Hemorrhage from Dual Circulation Pulmonary Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia

    OpenAIRE

    Sharma, Krishna B.; Lutz Forkert

    2004-01-01

    Pulmonary arteriovenous malformations (AVMs) are commonly supplied by the pulmonary arterial system and rarely by the systemic bronchial circulation. The authors outline the case of a young woman with pulmonary AVMs as part of hereditary hemorrhagic telangiectasia with the uncommon presentation of massive hemoptysis. Management of her recurrent, life-threatening pulmonary hemorrhage was complicated by pulmonary AVMs that were supplied by both the pulmonary and systemic bronchial arterial circ...

  16. Impact of the introduction of a guideline on the targeted detection of hereditary haemochromatosis.

    OpenAIRE

    Jacobs, E.M.G.; Meulendijks, C F M; Elving, L.D.; van der Wilt, G. J.; Swinkels, D W

    2005-01-01

    BACKGROUND: In 1998 a clinical guideline for the targeted, accurate and early detection and treatment of HFE-related hereditary haemochromatosis (HH), which comprises a test for the causative HFE-gene mutations, was introduced in our outpatient department. METHODS: The impact of this guideline was evaluated retrospectively. Data were acquired from medical records of patients with discharge diagnosis codes suggestive of HH (n=878 patients), obtained from a period before (n=422) and after guide...

  17. Synopsis of the Dutch multidisciplinary guideline for the diagnosis and treatment of hereditary haemochromatosis.

    OpenAIRE

    Swinkels, D W; Jorna, A.T.; Raymakers, R.A.P.

    2007-01-01

    Hereditary haemochromatosis (HH) is a disease related to mutations in the HFE gene and can lead to progressive iron accumulation, especially in the liver, eventually resulting in organ damage. We have developed guidelines for the diagnosis and treatment of this disease according to CBO methodology (dutch institute for Healthcare Quality). The prevalence of clinical symptoms such as fatigue, arthropathies, impotence and diabetes mellitus among homozygotes was similar to that in a control popul...

  18. Erythrocyte membrane protein destabilization versus clinical outcome in 160 Portuguese Hereditary Spherocytosis patients

    OpenAIRE

    Rocha, Susana; Costa, Elísio; Rocha-Pereira, Petronila; Ferreira, Fátima; Cleto, Esmeralda; Barbot, José; Quintanilha, Alexandre; Belo, Luís; Santos-Silva, Alice

    2010-01-01

    Abstract Hereditary Spherocytosis (HS) is a haemolytic anaemia caused by erythrocyte protein membrane defects ? spectrin, ankyrin, band 3 or protein 4.2 ? that lead to membrane destabilization. Ours aims were to evaluate the prevalence of protein deficiencies and the role of membrane proteins or of membrane linked proteins in membrane disturbance and in HS clinical outcome. We studied 215 Portuguese individuals ? 203 from 71 families plus 12 individual unrelated subjects, and found...

  19. Systematic review: hereditary thrombophilia associated to pediatric strokes and cerebral palsy

    OpenAIRE

    Vinicius M. Torres; Vera A. Saddi

    2015-01-01

    OBJECTIVES: This review aimed to organize and consolidate the latest knowledge about mutations and genetic polymorphisms related to hereditary thrombophilia and their potential association with pediatric stroke and cerebral palsy (CP). SOURCES: Scientific articles published from 1993 to 2013, written in Portuguese, English, French, and Spanish, were selected and reviewed. The publications were searched in electronic databases, and also in the collections of local libraries. The terms "heredit...

  20. A very large Brazilian pedigree with 11778 Leber's hereditary optic neuropathy.

    OpenAIRE

    Sadun, Alfredo A.; Carelli, Valerio; Salomao, Solange R.; Berezovsky, Adriana; Quiros, Peter; Sadun, Federico; DeNegri, Anna-Maria; Andrade, Rafael; Schein, Stan; Belfort, Rubens

    2002-01-01

    PURPOSE: We conducted extensive epidemiological, neuro-ophthalmological, psychophysical, and blood examinations on a newly discovered, very large pedigree with molecular analysis showing mtDNA mutation for Leber's hereditary optic neuropathy (LHON). METHODS: Four patients representing four index cases from a remote area of Brazil were sent to Sao Paulo, where complete ophthalmological examinations strongly suggested LHON. Molecular analysis of their blood demonstrated that they were LHON, hom...

  1. Left Atrial Appendage Closure for Stroke Prevention in Patients with Atrial Fibrillation and Hereditary Hemorrhagic Telangiectasia

    OpenAIRE

    Sebastiaan Velthuis; Swaans, Martin J.; Mager, Johannes J.; Rensing, Benno J. W. M.; Lucas V. A. Boersma; Post, Martijn C.

    2012-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting millions of individuals worldwide, and a major risk factor for disabling cerebral embolic stroke. Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disorder, characterized by vascular abnormalities with high-bleeding tendency and therefore intolerance for oral anticoagulation. We report a case of percutaneous closure of the left atrial appendage, which might be a good alternative strategy in...

  2. Microflora and chemical composition of dental plaque from subjects with hereditary fructose intolerance.

    OpenAIRE

    Hoover, C I; Newbrun, E; Mettraux, G; Graf, H

    1980-01-01

    We compared the microbiological and chemical composition of dental plaque from subjects with hereditary fructose intolerance who restrict their dietary sugar intake with that of control subjects who do not. The two groups showed no significant differences in chemical composition of plaque: the mean protein, carbohydrate, calcium, magnesium, and phosphate contents were similar. Dental plaque from both groups contained similar numbers of total colony-forming units per microgram of plaque protei...

  3. Intrafamilial disclosure of risk for hereditary breast and ovarian cancer: points to consider

    OpenAIRE

    Black, Lee; McClellan, Kelly A.; Avard, Denise; Knoppers, Bartha Maria

    2012-01-01

    The primary goal of breast and ovarian cancer screening is to minimize the cases of advanced disease and therefore its mortality rate. For hereditary breast and ovarian cancer, one method to reach this goal is to disseminate genetic risk information among family members. However, experience tells us that this information does not always reach family members in a timely manner, if at all. There are many moving parts to a decision to disclose genetic risk information within a family, and the la...

  4. Cellular and Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss – A Common Hereditary Deafness

    OpenAIRE

    Wingard, Jeffrey C.; Zhao, Hong-Bo

    2015-01-01

    Hearing loss due to mutations in the connexin gene family, which encodes gap junctional proteins, is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2) mutations are responsible for ~50% of non-syndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. Recent experiments demonstrate th...

  5. Mitochondrial DNA Complex I and III Mutations Associated with Leber's Hereditary Optic Neuropathy

    OpenAIRE

    Brown, M D; Voljavec, A. S.; Lott, M T; Torroni, A.; Yang, C. C.; Wallace, D C

    1992-01-01

    Four new missense mutations have been identified through restriction analysis and sequencing of the mitochondrial DNAs (mtDNA) from Leber's hereditary optic neuropathy (LHON) patients who lacked the previously identified 11778 mutation. Each altered a conserved amino acid and correlated with the LHON phenotype in population and phylogenetic analyses. The nucleotide pair (np) 13708 mutation (G to A, ND5 gene) changed an alanine to a threonine and was found in 6/25 (24%) of non-11778 LHON pedig...

  6. Clinical and genetic features of International Collaborative Group-hereditary nonpolyposis colorectal cancer families and suspected hereditary nonpolyposis colorectal cancer families

    Institute of Scientific and Technical Information of China (English)

    袁瑛; 叶俊; 郑树

    2004-01-01

    Background Hereditary nonpolyposis colorectal cancer (HNPPC) is one of the most common genetic syndrome related with mutation of human mismatch repair genes. This study was to evaluate the clinical significance of suspected hereditary nonpolyposis colorectal cancer (sHNPCC) criteria I and the clinical and genetic features of International Collaborative Group-HNPCC (ICG-HNPCC) and sHNPCC families.Methods Twenty-nine ICG-HNPCC families fulfilling the Amsterdam criteria and 34 sHNPCC families fulfilling the sHNPCC criteria I were collected. PCR-SSCP and DNA sequencing analysis were employed to screen the germline mutations of the hMLH1 and hMSH2 genes in these families.Results The ICG group had more colorectal cancer (CRC) patients per family than did the suspected group (P0.05), mutation type, and mutation distribution. Comparison of the families with and without mutation showed no significant difference in CRC patients per family, Lynch classification, and tumor spectrum.Conclusions ICG-HNPCC and sHNPCC families that have similar clinical manifestations and genetic basis indicate a similar nature for cancer development. The application of sHNPCC criteria I will facilitate clinical diagnosis and treatment of small families.

  7. Comparison and evaluation of three screening tests of hereditary spherocytosis in Chinese patients.

    Science.gov (United States)

    Tao, Yi-feng; Deng, Zeng-fu; Liao, Lin; Qiu, Yu-ling; Chen, Wen-qiang; Lin, Fa-quan

    2015-05-01

    The objective of this study is to compare and evaluate the diagnostic value of hereditary spherocytosis (HS) by three screening tests, comparing mean spherical corpuscular volume (MSCV) to mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and flow cytometric osmotic fragility test. Peripheral blood was collected from 237 participators diagnosed at the First Affiliated Hospital of Guangxi Medical University, including 56 hereditary spherocytosis patients, 86 thalassemia patients, and 95 healthy people. The samples were examined by three tests, and the three screening tests were evaluated by the sensitivity and specificity of tests. The sensitivity was only 41.07%, and specificity was 94.47% when using MCHC >355 g/L as diagnostic criteria. The sensitivity was 89.28%, and specificity was 96.14% when using MSCV diagnostic threshold in flow cytometric osmotic fragility test, the sensitivity was 85.71% and the specificity was 97.24%. Flow cytometry osmotic fragility test or comparing MSCV to MCV combined with smear examination of peripheral red blood cells morphology can be a simple, practical, and accurate hereditary spherocytosis (HS) laboratory screening method. PMID:25501660

  8. Analysis of Hereditary Elliptocytosis with Decreased Binding of Eosin-5-maleimide to Red Blood Cells

    Directory of Open Access Journals (Sweden)

    Shin-ichiro Suemori

    2015-01-01

    Full Text Available Flow cytometric test for analyzing the eosin-5-maleimide (EMA binding to red blood cells has been believed to be a specific method for diagnosing hereditary spherocytosis (HS. However, it has been reported that diseases other than HS, such as hereditary pyropoikilocytosis (HPP and Southeast Asian ovalocytosis (SAO, which are forms in the category of hereditary elliptocytosis (HE, show decreased EMA binding to red blood cells. We analyzed EMA binding to red blood cells in 101 healthy control subjects and 42 HS patients and obtained a mean channel fluorescence (MCF cut-off value of 36.4 (sensitivity 0.97, specificity 0.95. Using this method, we also analyzed 12 HE patients. Among them, four HE patients showed the MCF at or below the cut-off value. It indicates that some HE patients have decreased EMA binding to red blood cells. Two of these four HE patients were classified as common HE, and two were spherocytic HE with reduced spectrin. This study demonstrates that, in addition to patients with HPP or SAO, some HE patients have decreased EMA binding to red blood cells.

  9. Utilization of the higher plants in a study on hereditary effect of low-dose irradiation

    International Nuclear Information System (INIS)

    Some problems in a study of hereditary effect of low-dose irradiation, which used the higher plants (tradescantia, peas, etc.) as materials, were mentioned. Conditions to be used as materials were mentioned as follows: 1) the materials must have high radio-sensitivity, 2) the natural mutation of the materials must be low, 3) hereditary uniformity and stability of genes in the materials were important, and 4) in case of considering the materials as environmental radiation monitors, the observation period must be long and the duration from exposure to detection of mutation must be short. Tradescantia has most of these conditions, but the greatest fault is that the object of its observation is mutation of somatic cells, and hereditary study is impossible. Therefore, it is necessary to find out other materials in order to solve the problem whether there is a difference in relative frequency of chromosomal abnormalities, which occurrs in germinal cells and is transmitted to posterity, between low and high doses or not. (Serizawa, K.)

  10. Hereditary papillary renal cell carcinoma primarily diagnosed in a cervical lymph node: a case report of a 30-year-old woman with multiple metastases

    OpenAIRE

    Behnes Carl Ludwig; Schlegel Christina; Shoukier Moneef; Magiera Isabella; Henschke Frank; Schwarz Alexander; Bremmer Felix; Loertzer Hagen

    2013-01-01

    Abstract Background Papillary renal cell carcinoma is a rare cancer. Some cases can be attributed to individuals with hereditary renal cell carcinomas usually consisting of the clear cell subtype. In addition, two syndromes with hereditary papillary renal cell carcinoma have been described. One is the hereditary leiomyomatosis and renal cell carcinoma, which is characterized by cutaneous and uterine leiomyomas and renal cell carcinoma mostly consisting of the papillary renal cell carcinoma ty...

  11. 遗传性小脑共济失调的MRI表现附2个家系报告%MRI Findings of Hereditary Cerebellar Ataxia

    Institute of Scientific and Technical Information of China (English)

    董江宁; 刘啸峰; 马力

    2004-01-01

    遗传性小脑共济失调(hereditary cerebellar ataxia,HCA),又称遗传性痉挛性共济失调(hereditary spastic ataxia,HSA),属介于脊髓型至脑干小脑型及小脑型之间的遗传性共济失调(hereditary ataxia,HA),包括Sanger-Brown型、橄榄桥脑小脑萎缩(olivopontocerebellar atrophy,

  12. Radiobiology in clinical radiation therapy - Part IV: Long term risks - Carcinogenic, hereditary, and teratogenetic effects

    International Nuclear Information System (INIS)

    The long-term risks induced by radiation are of much concern to patients and clinicians alike. As an example, perceived radiation risks are frequently cited in a woman's decision to choose a radical mastectomy over lumpectomy + radiation. In consequence, the actual radiation risks are often considerably overstated, or unreasonably downplayed. In this lecture we will discuss just what is known about the long term risks following radiotherapy, both from the human experience and from the laboratory. We will discuss risks both to the patient and to radiotherapy personnel. A good deal is known about the carcinogenic effects of high and low doses of radiation, in large part thanks to the careful study of the survivors of the atomic bombing in Japan, as well as studies of individuals exposed to medical x rays. It is possible to make an estimate, which is probably good to within a factor of, perhaps, three to five, of the cancer risks faced by a patient of a particular age and sex who is going to undergo a particular radiotherapeutic regimen. It is also possible to make an estimate of the risks faced by radiotherapy and nursing staff exposed to low doses. Brachytherapy related risk estimates are likely to be somewhat more uncertain, due to the poorly known sparing effects of the low dose rates used; for the radiotherapy personnel in brachytherapy, because of the doses which can be received, the risks can be quite significant. A recent complication in external-beam radiotherapy is the advent of high-energy linacs, which can produce a significant fast neutron dose which, dose for dose, may be ten to fifty times more carcinogenic than gamma rays. Data relating to the risks of hereditary effects of radiation come almost entirely from laboratory experiments in animals. Studies involving several million mice form the basis of most of our current understanding of hereditary effects. The results of these studies indicate that radiation is a relatively inefficient mutagen. The

  13. Radiobiology in clinical radiation therapy: Long term risks - Carcinogenic, hereditary, and teratogenetic effects

    International Nuclear Information System (INIS)

    The long-term risks induced by radiation are of much concern to patients and clinicians alike. As an example, perceived radiation risks are frequently cited in a woman's decision to choose a radical mastectomy over lumpectomy + radiation. In consequence, the actual radiation risks are often considerably overstated, or unreasonably downplayed. In this lecture we will discuss just what is known about the long term risks following radiotherapy, both from the human experience and from the laboratory. We will discuss risks both to the patient and to radiotherapy personnel. A good deal is known about the carcinogenic effects of high and low doses of radiation, in large part thanks to the careful study of the survivors of the atomic bombing in Japan, as well as studies of individuals exposed to medical x rays. It is possible to make an estimate, which is probably good to within a factor of, perhaps, three to five, of the cancer risks faced by a patient of a particular age and sex who is going to undergo a particular radiotherapeutic regimen. It is also possible to make an estimate of the risks faced by radiotherapy and nursing staff exposed to low doses. Brachytherapy related risk estimates are likely to be somewhat more uncertain, due to the poorly known sparing effects of the low dose rates used; for the radiotherapy personnel in brachytherapy, because of the doses which can be received, the risks can be quite significant. A recent complication in external-beam radiotherapy is the advent of high-energy linacs, which can produce a significant fast neutron dose which, dose for dose, may be ten to fifty times more carcinogenic than gamma rays. Data relating to the risks of hereditary effects of radiation come almost entirely from laboratory experiments in animals. Studies involving several million mice form the basis of most of our current understanding of hereditary effects. The results of these studies indicate that radiation is a relatively inefficient mutagen. The

  14. Visão atual da hemocromatose hereditária Current approach to hereditary hemochromatosis

    Directory of Open Access Journals (Sweden)

    Rodolfo Delfini Cançado

    2010-01-01

    Full Text Available A hemocromatose hereditária (HH está relacionada a diversos distúrbios do metabolismo do ferro que ocasionam sua sobrecarga tecidual. A HH clássica está associada às mutações do gene HFE (homozigose para C282Y ou duplo heterozigose para C282Y/H63D, sendo encontrada quase exclusivamente em descendentes do norte Europeu. A hemocromatose hereditária, quando não relacionada ao gene HFE, é causada por mutações de outros genes, recentemente identificados, envolvidos no metabolismo do ferro. Hepcedina é o hormônio regulador do ferro que inibe a ferroportina, proteína exportadora de ferro dos enterócitos e dos macrófagos; um defeito na expressão do gene da hepcedina ou na sua função costuma ser a causa da maioria dos tipos de hemocromatose hereditária. Os alvos acometidos pela HH são órgãos e tecidos - fígado, coração, pâncreas, articulações e pele -, sendo a cirrose e o diabetes melito os sinais tardios da doença em pacientes com expressivo aumento da concentração hepática de ferro. Pacientes com diagnóstico estabelecido de hemocromatose hereditária e sobrecarga de ferro devem ser tratados com flebotomia para a obtenção de depleção do ferro do organismo; em seguida, com flebotomia de manutenção. As causas mais frequentes de morte por hemocromatose hereditária são câncer hepático, cirrose, miocardiopatia e diabete; entretanto, pacientes submetidos à depleção do ferro de maneira satisfatória e antes do desenvolvimento da cirrose ou da diabete podem ter sobrevida normal.Hereditary hemochromatosis refers to several inherited disorders of the iron metabolism that lead to tissue iron overload. Classical hereditary hemochromatosis is associated with mutations of the HFE gene (C282Y homozygotes or C282Y/H63D compound heterozygotes and is almost exclusively found in populations of northern European descent. Non-HFE-associated hereditary hemochromatosis is caused by mutations in other recently identified genes

  15. Cancer risk among patients with hereditary muscular dystrophies:a population-based study in Taiwan, 1997-2009

    Institute of Scientific and Technical Information of China (English)

    Gen-Min Lin; Yi-Hwei Li

    2014-01-01

    Muscular dystrophies (MD) comprise a heterogeneous group of hereditary myopathic diseases. In this group, myotonic MD is associated with an increased cancer risk. However, the cancer risk in other types of MD is unclear. To address this gap in knowledge, we assessed data obtained from the Taiwan Health Insurance Program database. A total of 1,272 patients with MD diagnosed between 1997 and 2009 were enrol ed. They were fol owed up for cancer during the same period by record linkage with the cancer certification in Taiwan. Age- and sex-standardized incidence ratios (SIRs) of overall and site-specific cancers were calculated. For congenital and progressive hereditary MD, there were 685 and 505 cases (males:69.5%and 80.6%), the median ages at diagnosis were 16 and 13 years, and the mean fol ow-up durations were 7.12 and 5.06 years, respectively. In addition, cancers were developed in 10 patients with congenital MD and 3 patients with progressive hereditary MD. Female MD patients exhibited an increased cancer risk, yielding an SIR of 3.37 [95%confidence interval (CI)=1.38-8.25] in congenital MD and 2.95 (95% CI = 0.95-9.19) in hereditary progressive MD. Site-specific cancer SIRs were not powered to be significantly different. In conclusion, genetic defects in hereditary MD may increase cancer risks in females and a sex difference should be further investigated.

  16. Successful C1 inhibitor short-term prophylaxis during redo mitral valve replacement in a patient with hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Coleman Suzanne

    2010-10-01

    Full Text Available Abstract Hereditary angioedema is characterized by sudden episodes of nonpitting edema that cause discomfort and pain. Typically the extremities, genitalia, trunk, gastrointestinal tract, face, and larynx are affected by attacks of swelling. Laryngeal swelling carries significant risk for asphyxiation. The disease results from mutations in the C1 esterase inhibitor gene that cause C1 esterase inhibitor deficiency. Attacks of hereditary angioedema result from contact, complement, and fibrinolytic plasma cascade activation, where C1 esterase inhibitor irreversibly binds substrates. Patients with hereditary angioedema cannot replenish C1 esterase inhibitor levels on pace with its binding. When C1 esterase inhibitor is depleted in these patients, vasoactive plasma cascade products cause swelling attacks. Trauma is a known trigger for hereditary angioedema attacks, and patients have been denied surgical procedures because of this risk. However, uncomplicated surgeries have been reported. Appropriate prophylaxis can reduce peri-operative morbidity in these patients, despite proteolytic cascade and complement activation during surgical trauma. We report a case of successful short-term prophylaxis with C1 esterase inhibitor in a 51-year-old man with hereditary angioedema who underwent redo mitral valve reconstructive surgery.

  17. The genus zeta function of hereditary orders in central simple algebras over global fields

    Science.gov (United States)

    Denert, M.

    1990-01-01

    Louis Solomon introduced the notion of a zeta function {ζ_θ }(s) of an order θ in a finite-dimensional central simple K-algebra A, with K a number field or its completion {K_P} (P a non-Archimedean prime in K). In several papers, C. J. Bushnell and I. Reiner have developed the theory of zeta functions and they gave explicit formulae in some special cases. One important property of these zeta functions is the Euler product, which implies that in order to calculate {ζ_θ }(s) , it is sufficient to consider the zeta function of local orders {θ _P} . However, since these local orders {θ _P} are in general not principal ideal domains, their zeta function is a finite sum of so-called 'partial zeta functions'. The most complicated term is the 'genus zeta function', {Z_{{θ _P}}}(s) , which is related to the free {θ _P} -ideals. I. Reiner and C. J. Bushnell calculated the genus zeta function for hereditary orders in quaternion algebras (i.e., [A:K] = 4 ). The authors mention the general case but they remark that the calculations are cumbersome. In this paper we derive an explicit method to calculate the genus zeta function {Z_{{θ _P}}}(s) of any local hereditary order {θ _P} in a central simple algebra over a local field. We obtain {Z_{{θ _P}}}(s) as a finite sum of explicit terms which can be calculated with a computer. We make some remarks on the programming of the formula and give a short list of examples. The genus zeta function of the minimal hereditary orders (corresponding to the partition (1, 1, ... , 1) of n) seems to have a surprising property. In all examples, the nominator of this zeta function is a generating function for the q-Eulerian polynomials. We conclude with some remarks on a conjectured identity.

  18. Hereditary hypertriglyceridemic rat: a suitable model of cardiovascular disease and metabolic syndrome?

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Pecháňová, Olga; Čačányiová, S.; Cebová, M.; Kristek, F.; Török, J.; Šimko, F.; Dobešová, Zdenka; Kuneš, Jaroslav

    2006-01-01

    Roč. 55, č. S1 (2006), S49-S63. ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA MZd(CZ) NR7786 Grant ostatní: VEGA(SK) 2/6148/26; VEGA(SK) 2/6150/26; VEGA(SK) 1/3429/06; VEGA(SK) 2/3139/26 Institutional research plan: CEZ:AV0Z50110509 Keywords : hereditary hypertriglyceridemic rat * insulin resistance * hypertension Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  19. Hereditary retinal eye diseases in childhood and youth affecting the central retina

    Directory of Open Access Journals (Sweden)

    Martin M Nentwich

    2013-01-01

    Classic examinations for patients suffering from hereditary retinal dystrophies of the central retina are funduscopy - also using red-free light - visual-field tests, electrophysiologic tests as electro-retinogram [ERG] and multifocal ERG and tests evaluating color vision. Recently, new imaging modalities have been introduced into the clinical practice. The significance of these new methods such as high-resolution spectral-domain optic coherence tomography [SD-OCT] and fundus autofluorescence will be discussed as well as "next generation sequencing" as a new method for the analysis of genetic mutations in a larger number of patients.

  20. REEPing the benefits of an animal model of hereditary spastic paraplegia

    OpenAIRE

    Deutch, Ariel Y.; Hedera, Peter; Roger J Colbran

    2013-01-01

    The hereditary spastic paraplegias (HSPs) are characterized by spasticity of the leg muscles due to axonal degeneration of corticospinal neurons. Beetz et al. report that the core motor phenotype and axonal pathology of HSPs are recapitulated in mice lacking the HSP-associated gene Reep1. REEP1 is shown to regulate ER structure in motor cortex neurons. The Reep1 knockout mouse should be a very useful model in which to study the mechanisms of progressive axon loss in HSPs and other disorders.

  1. Hereditary and Sporadic Papillary Renal Carcinomas with c-met Mutations Share a Distinct Morphological Phenotype

    OpenAIRE

    Irina A. Lubensky; Schmidt, Laura; Zhuang, Zhengping; Weirich, Gregor; Pack, Svetlana; Zambrano, Norman; WALTHER, McCLELLAN M.; Choyke, Peter; Linehan, W. Marston; Zbar, Berton

    1999-01-01

    Germline mutations of c-met oncogene at 7q31 have been detected in patients with hereditary papillary renal cell carcinoma. In addition, c-met mutations were shown to play a role in 13% of patients with papillary renal cell carcinoma and no family history of renal tumors. The histopathology of papillary renal cell carcinoma with c-met mutations has not been previously described. We analyzed the histopathology of 103 bilateral archival papillary renal cell carcinomas and 4 metastases in 29 pat...

  2. The Mitochondrial DNA Mutation at Position 11778 in Chinese Families with Leber's Hereditary Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    We amplified the 340 bp of mitochondrial DMA (mtDNA) by PCR including the recognized sequence of restriction enzyme of SfaN I . After amplification and digestion of SfaN I , two bands of 190 bp and 150 bp appeared in the mtDNA of four normal individuals but only one band of 340 bp appeared in the mtDNA with the mutation of G to A at the site of the nucleotide 11778 because such mutation destroyed the recognized sequence of SfaN I . We studied the mtDNAs of the patients with Leber's hereditary optic neur...

  3. Inheritance of Hereditary Persistence of Fetal Haemoglobin (HPFH) in a Family of Western Odisha, India

    OpenAIRE

    Patel, Siris; Dehury, Snehadhini; Purohit, Prasanta; Meher, Satyabrata; Das, Kishalaya

    2015-01-01

    Hereditary persistence of foetal haemoglobin (HPFH) is a rare inherited haemoglobin disorders in India. We encountered five cases of HPFH-3 in heterozygous condition in a single family of western Odisha, India. All the cases had raised % HbF (26.1±3.23%) with pancellular distribution of HbF in erythrocytes. There were no abnormalities found in the red cell indices. All the cases were asymptomatic till date with normal growth and development. Molecular confirmation of this haemoglobin disorder...

  4. Reversible pancytopenia and immunodeficiency in a patient with hereditary folate malabsorption.

    Science.gov (United States)

    Erlacher, Miriam; Grünert, Sarah Catharina; Cseh, Annamaria; Steinfeld, Robert; Salzer, Ulrich; Lausch, Ekkehart; Nosswitz, Ulrike; Dückers, Gregor; Niehues, Tim; Ehl, Stephan; Niemeyer, Charlotte Marie; Speckmann, Carsten

    2015-06-01

    Mutations in SLC46A1 result in a defect of the proton coupled folate transporter (PCFT) and are the basis of hereditary folate malabsorption (HFM). Patients with HFM frequently present with neurodevelopmental delay and megaloblastic anemia. Some cases may be complicated by additional lymphopenia and immunodeficiency. We report a patient with a new homozygous mutation in the SLC46A1 gene. The boy presented with early-onset pancytopenia and secondary immunodeficiency. We provide clinical and molecular observations that extend the phenotypic description of HFM and highlight diagnostic as well as therapeutic pitfalls in this rare condition. PMID:25504888

  5. Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment.

    Science.gov (United States)

    Zeerleder, Sacha; Levi, Marcel

    2016-06-01

    Uncontrolled generation of bradykinin (BK) due to insufficient levels of protease inhibitors controlling contact phase (CP) activation, increased activity of CP proteins, and/or inadequate degradation of BK into inactive peptides increases vascular permeability via BK-receptor 2 (BKR2) and results in subcutaneous and submucosal edema formation. Hereditary and acquired angioedema due to C1-inhibitor deficiency (C1-INH-HAE and -AAE) are diseases characterized by serious and potentially fatal attacks of subcutaneous and submucosal edemas of upper airways, facial structures, abdomen, and extremities, due to inadequate control of BK generation. A decreased activity of C1-inhibitor is the hallmark of C1-INH-HAE (types 1 and 2) due to a mutation in the C1-inhibitor gene, whereas the deficiency in C1-inhibitor in C1-INH-AAE is the result of autoimmune phenomena. In HAE with normal C1-inhibitor, a significant percentage of patients have an increased activity of factor XIIa due to a FXII mutation (FXII-HAE). Treatment of C1-inhibitor-dependent angioedema focuses on restoring control of BK generation by inhibition of CP proteases by correcting the balance between CP inhibitors and BK breakdown or by inhibition of BK-mediated effects at the BKR2 on endothelial cells. This review will address the pathophysiology, clinical picture, diagnosis and available treatment in C1-inhibitor-dependent angioedema focusing on BK-release and its regulation. Key Messages Inadequate control of bradykinin formation results in the formation of characteristic subcutaneous and submucosal edemas of the skin, upper airways, facial structures, abdomen and extremities as seen in hereditary and acquired C1-inhibitor-dependent angioedema. Diagnosis of hereditary and acquired C1-inhibitor-dependent angioedema may be troublesome as illustrated by the fact that there is a significant delay in diagnosis; a certain grade of suspicion is therefore crucial for quick diagnosis. Submucosal edema formation in

  6. Hereditary angioedema presenting as irritable bowel syndrome: a case of early closure

    Directory of Open Access Journals (Sweden)

    Karim M. Benrajab

    2015-10-01

    Full Text Available Abdominal pain is one of the most common reasons for outpatient and emergency department visits. We present one such case of early closure in a 32-year-old male with recurrent abdominal pain who was diagnosed with irritable bowel syndrome (IBS. Family history was suspicious for hereditary angioedema (HAE. The HAE workup came back positive, and the patient was started on prophylactic therapy, which led to an improvement in symptoms and quality of life. The purpose of this case is to create awareness among physicians to test for HAE in patients diagnosed with IBS who, based on their history or physical examination, have clinical suspicion for HAE.

  7. Neurofeedback in Hereditary Angioedema: A Single Case Study of Symptom Reduction.

    Science.gov (United States)

    Burns, Stephanie T

    2015-09-01

    Neurofeedback training was performed consisting of rewarding and encouraging 12-15 Hz brainwaves (SMR), while simultaneously discouraging 4-7 Hz brainwaves (theta) and 22-30 Hz brainwaves (high beta) in the right dorsal posterior quadrant of the brain (T4, P4) for 20 half-hour NFB sessions to determine the impact on cortisol levels, DHEA-S levels, scores on the Symptom Checklist-90-R (SCL-90-R), the quality of life inventory, and acute attack medication usage for a Hereditary Angioedema patient. PMID:25958076

  8. [Treatment of drugs-associated non-hereditary angioedema mediated by bradykinin].

    Science.gov (United States)

    Muller, Yannick; Harr, Thomas

    2016-01-13

    Angioedema is a deep intradermal or sub-cutaneous edema, which can be mediated by histamine, bradykinin or mixture of both components. The aims of this review are to describe the clinical approach and diagnosis of non-hereditary bradykinin-mediated angioedema induced by drugs such as: angiotensin-converting inhibitor, sartan, gliptins, rapamycin or some thrombolytic reagents and renin inhibitors. Furthermore, we will discuss the drug management of these angioedema, which is mainly based on C1 inhibitor concentrate or icatibant administration. PMID:26946694

  9. Hereditary angioedema presenting as irritable bowel syndrome: a case of early closure

    Science.gov (United States)

    Benrajab, Karim M.; Singh, Gurkeerat; Obah, Eugene

    2015-01-01

    Abdominal pain is one of the most common reasons for outpatient and emergency department visits. We present one such case of early closure in a 32-year-old male with recurrent abdominal pain who was diagnosed with irritable bowel syndrome (IBS). Family history was suspicious for hereditary angioedema (HAE). The HAE workup came back positive, and the patient was started on prophylactic therapy, which led to an improvement in symptoms and quality of life. The purpose of this case is to create awareness among physicians to test for HAE in patients diagnosed with IBS who, based on their history or physical examination, have clinical suspicion for HAE. PMID:26486119

  10. Cutaneous necrosis in pregnancy secondary to activated protein C resistance in hereditary angioedema.

    Science.gov (United States)

    Perkins, W; Downie, I; Keefe, M; Chisholm, M

    1995-04-01

    A 26-year-old woman with hereditary angineurotic oedema (HAE) presented at 22 weeks gestation with severe cutaneous necrosis similar to that seen in coumarin skin necrosis. Protein S deficiency secondary to HAE and pregnancy was postulated. Treatment with heparin, C1-inhibitor concentrates, systemic steroids and surgical debridement resulted in a successful outcome for both mother and child. Subsequent investigations revealed normal levels of protein C, antithrombin III, total protein S, free protein S but reduced function protein S activity with evidence of activated protein C resistance. Cutaneous necrosis has not been reported in associated with activated protein C resistance previously and the possible mechanisms are discussed. PMID:7745572

  11. Modified descemet′s stripping automated endothelial keratoplasty for congenital hereditary endothelial dystrophy

    Directory of Open Access Journals (Sweden)

    Mahmoodreza Panahi-Bazaz

    2014-01-01

    Full Text Available A 19-year-old male with congenital hereditary endothelial dystrophy (CHED presented with severe bilateral corneal clouding precluding any view of the intraocular structures. He underwent modified Descemet′s stripping automated endothelial keratoplasty (DSAEK technique including a suture pull-through technique to prevent lens damage. Surgery resulted in progressive clearing of the cornea and decreased corneal thickness. Visual acuity increased from hand motions preoperatively to counting fingers at 4 m after 4 months. DSAEK can be successfully performed in phakic eyes with CHED as an alternative to penetrating keratoplasty. It has the advantage of less wound problems and better preservation of globe integrity especially in children.

  12. A new polymorphism for the RI22H mutation in hereditary pancreatitis

    OpenAIRE

    Howes, N.; Greenhalf, W; Rutherford, S.; O'Donnell, M; Mountford, R; Ellis, I; WHITCOMB, D; Imrie, C; Drumm, B; Neoptolemos, J.

    2001-01-01

    BACKGROUND AND AIMS—Hereditary pancreatitis (HP) is a rare form of recurrent acute and chronic pancreatitis. Mutations in the cationic trypsinogen (protease serine 1, PRSS1) gene have been identified as causing HP. The R122H (previously known as R117H) mutation is the commonest and can be detected by a single and rapid polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) based technique using the AflIII enzyme. This test however may give a false negative result in the...

  13. Application of 51Cr in examination of patients with hereditary microspherocytic hemolytic anemia

    International Nuclear Information System (INIS)

    A total of 20 patients with hereditary microspherocytic hemolytic anemia were examined by the method of erythrocyte labelling with 51Cr. The survival rate of the erythrocytes appeared to be shortened in all the patients. The degree of this shortening corresponded to the severity of the clinico-hematological signs of hemolysis. The sequestrating capacity of the spleen elevated in all patients increased as the organ enlarged. The efficacy of splenectomy was checked in 11 patients by a repeated control examination with 51Cr. The given test can be successfully used for diagnosis of hemolytic conditions, evaluation of their clinical course severity, prognosis and assessment of splenectomy efficacy

  14. A Study on the Ultrastructure and Gene Location of Hereditary Gingival Fibromatosis

    Institute of Scientific and Technical Information of China (English)

    杨明华; 张东生; 肖尚喜; 武影; 郑际烈; 孔祥银

    2002-01-01

    Objective To ascertain the histological characteristics of hereditary gingival fibromatosis and the location of HGF gene. Methods A pedigree analysis of HGF was made. The ultrastructure of gingival overgrown tissue was observed by electron microscopy (EMS) and the location of the HGF gene defined with microsatellite markers. Results The HGF consisted of coarse collagen bundles and fibrocytes, epithelial cells, smooth muscle cells, etc. were abnormally arranged; the HGF locus had been mapped to chromosome 5q13-q22. Conclusion The gingival pathological changes resemble "hamartoma" and the findings have implications for identification of the underlying genetic basis of HGF.

  15. Dyspnea with anemia turned out to be a case of hereditary hemorrhagic telangiectasia

    Directory of Open Access Journals (Sweden)

    Amitabha Sengupta

    2013-01-01

    Full Text Available Hereditary hemorrhagic telangiectasia (HHT is a rare autosomal dominant inherited disorder of the vascular system. It can be asymptomatic but when symptomatic most common presentation being epistaxis. It can involve any organs of the body like lungs, skin, liver brain, GI mucosa etc. We are reporting a case of HHT presented to us with dyspnea and severe anemia. He had arteriovenous malformations of different visceral organs and telangiectasia of skin along with presence of similar history in first-degree relatives.

  16. Hereditary Hemorrhagic Telangiectasia Presenting as High Output Cardiac Failure during Pregnancy

    Directory of Open Access Journals (Sweden)

    Tareq Goussous

    2009-01-01

    Full Text Available High-output cardiac failure secondary to hepatic involvement is a rare complication of hereditary hemorrhagic telangiectasia (HHT. Here we report a 43-year-old woman who presented at 29 weeks gestation of her second pregnancy with complications of right-sided heart failure and preterm labor. After delivery via cesarean section, the patient was found to have intrahepatic arteriovenous malformations through non-invasive imaging. Subsequently, a family history of vascular malformations and epistaxis was elucidated and a diagnosis of HHT was made. This case is presented, along with a review of the literature and discussion of hepatic involvement in HHT with particular focus on the pregnant patient.

  17. Global Gene Expression Profiling of Telangiectasial Tissue from Patients with Hereditary Haemorrhagic Telangiectasia

    DEFF Research Database (Denmark)

    Tørring, Pernille M; Larsen, Martin Jakob; Kjeldsen, Anette D;

    2015-01-01

    Hereditary haemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, is predominantly caused by mutations in ENG and ACVRL1, which are part of the transforming growth factor beta (TGF-β) signalling pathway. HHT is characterized by the presence of mucocutaneous telangiectases...... and arteriovenous malformations in visceral organs, primarily the lungs, brain and liver. The most common symptom in HHT is epistaxis originating from nasal telangiectasia, which can be difficult to prevent and can lead to severe anaemia. The clinical manifestations of HHT are extremely variable, even...

  18. Hepcidin levels in hereditary hyperferritinemia:Insights into the iron-sensing mechanism in hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Jayantha; Arnold; Arvind; Sangwaiya; Vijay; Manglam; Mark; Thursz; Caroline; Beaumont; Caroline; Kannengiesser; Mark; Busbridge

    2010-01-01

    AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the L-ferritin gene,were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay,respectively,and measurements were compared with levels in serum from 25 healthy volunteers(14 females),mean age 36±11.9 years.RESULTS:The serum hepcidin an...

  19. Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overload

    OpenAIRE

    Porto, G.; CARDOSO, C.S.; Gordeuk, V; Cruz, E.; Fraga, J.; Areias, J; Oliveira, J. C.; Bravo, F. (Federico); GANGAIDZO, I.T.; MACPHAIL, A.P.; GOMO, Z.A.; MOYO, V.M.; Melo, G.; Silva, C.; JUSTICA, B.

    2001-01-01

    Eur J Haematol. 2001 Aug;67(2):110-8. Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overload. Porto G, Cardoso CS, Gordeuk V, Cruz E, Fraga J, Areias J, Oliveira JC, Bravo F, Gangaidzo IT, MacPhail AP, Gomo ZA, Moyo VM, Melo G, Silva C, Justiça B, de Sousa M. Haematology, Santo António General Hospital, Porto, Portugal. Abstract To identify a new marker of expression of diseas...

  20. Advantages of a miniature pig model in research on human hereditary hearing loss

    Institute of Scientific and Technical Information of China (English)

    Weiwei Guo; Shi-ming Yang

    2015-01-01

    In medical laboratory animals, the pig is the closest species to human in evolution, except for primates. As an animal model, the pig is highly concerned by many scientists, including comparative biology, developmental biology, medical genetics. Rodents as animal model for human hearing defects has are poor producibility and reliability, due to differences in anatomical structure, evolutionary rate and metabolic rate, but these happens to be the advantages of the pig model. In this paper, we will summarize the application of miniature pig in the study of human hereditary deafness.