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Dehydrogenase Deficiency (dehydrogenase + deficiency)
Kinds of Dehydrogenase Deficiency Selected AbstractsGlucose-6-Phosphate Dehydrogenase Deficiency Associated Stuttering Priapism: Report of a CaseTHE JOURNAL OF SEXUAL MEDICINE, Issue 12 2008David S. Finley MD ABSTRACT Aim., Stuttering priapism is an uncommon form of recurrent priapism whose etiology if often unknown. To date, there has been one report of a patient with stuttering priapism and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Herein we describe the second-known case of recurrent priapism in a patient with G6PD deficiency. The pathophysiology of G6PD deficiency and its potential to cause priapism is reviewed. Methods., A case report is described of a 29-year-old African-American man with G6PD deficiency who presented with numerous episodes of recurrent ischemic priapism. Clinical data was reviewed. Results., Despite medical management with gonadotropin-releasing hormone (GnRH) agonist, an antiandrogen, and baclofen, he required several surgical procedures which also ultimately failed. A continuous phosphodiesterase type-5 inhibitor (PDE5) was started and the patient had no recurrences at 3-month follow-up. Conclusion., Idiopathic recurrent priapism may be explained by underlying hemolytic anemia associated with G6PD deficiency. Several possible mechanisms exist to explain this association, including hyperviscosity, direct endothelial dysfunction secondary to bare hemoglobin vasculotoxicity, and relative nitric oxide deficiency causing vasoconstriction and vascular smooth muscle proliferation. Finley DS. Glucose-6-phosphate dehydrogenase deficiency associated stuttering priapism: Report of a case. J Sex Med **;**:**,**. [source] Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype,phenotype relationshipHUMAN MUTATION, Issue 3 2001Niels Gregersen Abstract Mutation analysis of metabolic disorders, such as the fatty acid oxidation defects, offers an additional, and often superior, tool for specific diagnosis compared to traditional enzymatic assays. With the advancement of the structural part of the Human Genome Project and the creation of mutation databases, procedures for convenient and reliable genetic analyses are being developed. The most straightforward application of mutation analysis is to specific diagnoses in suspected patients, particularly in the context of family studies and for prenatal/preimplantation analysis. In addition, from these practical uses emerges the possibility to study genotype,phenotype relationships and investigate the molecular pathogenesis resulting from specific mutations or groups of mutations. In the present review we summarize current knowledge regarding genotype,phenotype relationships in three disorders of mitochondrial fatty acid oxidation: very-long chain acyl-CoA dehydrogenase (VLCAD, also ACADVL), medium-chain acyl-CoA dehydrogenase (MCAD, also ACADM), and short-chain acyl-CoA dehydrogenase (SCAD, also ACADS) deficiencies. On the basis of this knowledge we discuss current understanding of the structural implications of mutation type, as well as the modulating effect of the mitochondrial protein quality control systems, composed of molecular chaperones and intracellular proteases. We propose that the unraveling of the genetic and cellular determinants of the modulating effects of protein quality control systems may help to assess the balance between genetic and environmental factors in the clinical expression of a given mutation. The realization that the effect of the monogene, such as disease-causing mutations in the VLCAD, MCAD, and SCAD genes, may be modified by variations in other genes presages the need for profile analyses of additional genetic variations. The rapid development of mutation detection systems, such as the chip technologies, makes such profile analyses feasible. However, it remains to be seen to what extent mutation analysis will be used for diagnosis of fatty acid oxidation defects and other metabolic disorders. Hum Mutat 18:169,189, 2001. © 2001 Wiley-Liss, Inc. [source] Investigation of prolonged neonatal jaundiceACTA PAEDIATRICA, Issue 6 2000S Hannam Jaundice persisting beyond 14 d of age (prolonged jaundice) can be a sign of serious underlying liver disease. Protocols for investigating prolonged jaundice vary in complexity and the yield from screening has not been assessed. In order to address these issues, we carried out a prospective study of term infants referred to our neonatal unit with prolonged jaundice over an 18 mo period. Infants were examined by a paediatrician and had the following investigations: a total and conjugated serum bilirubin, liver function tests, full blood count, packed cell volume, group and Coombs' test, thyroid function tests, glucose-6-phosphate dehydrogenase levels and urine for culture. One-hundred-and-fifty-four infants were referred with prolonged jaundice out of 7139 live births during the study period. Nine infants were referred to other paediatric specialties. One infant had a conjugated hyperbilirubinaemia, giving an incidence of conjugated hyperbilirubinaemia of 0.14 per 1000 live births. Diagnoses included: giant cell hepatitis (n= 1), hepatoblastoma (n= 1), trisomy 9p (n= 1), urinary tract infections (n= 2), glucose-6-phosphate dehydrogenase deficiency (n= 3) and failure to regain birthweight (n= 1). Conclusions: In conclusion, a large number of infants referred to hospital for prolonged jaundice screening had detectable problems. The number of investigations may safely be reduced to: a total and conjugated bilirubin, packed cell volume, glucose-6-phosphate dehydrogenase level (where appropriate), a urine for culture and inspection of a recent stool sample for bile pigmentation. Clinical examination by a paediatrician has a vital role in the screening process. [source] Potentiation of 3-hydroxyglutarate neurotoxicity following induction of astrocytic iNOS in neonatal rat hippocampal culturesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001Stefan Kölker Abstract Neuronal damage in glutaryl-CoA dehydrogenase deficiency (GDD) has previously been addressed to N- methyl- d -aspartate (NMDA) receptor-mediated neurotoxicity of the accumulating neurotoxic metabolite 3-hydroxyglutarate. However, acute encephalopathic crises in GDD patients are typically precipitated by febrile illness or even routine vaccinations, suggesting a potentiating role of inflammatory cytokines. In the present study we investigated the effect of interleukin-1, and interferon-, on 3-hydroxyglutarate toxicity in rat cortical astrocyte cultures and neonatal rat hippocampal cultures. A cotreatment of both culture systems with interleukin-1, and interferon-, induced the protein expression of astrocytic inducible nitric oxide synthase (iNOS), resulting in increased nitric oxide (NO) production. Cytokine pretreatment alone had no effect on cell viability but potentiated 3-hydroxyglutarate neurotoxicity. NOS inhibition by aminoguanidine and L-NAME prevented an iNOS-mediated potentiation of 3-hydroxyglutarate neurotoxicity but failed to protect neurons against 3-hydroxyglutarate alone. In contrast, superoxide dismutase/catalase as well as MK-801 prevented toxicity of 3-hydroxyglutarate alone as well as its potentiation by iNOS, supporting a central role of NMDA receptor stimulation with subsequently increased superoxide anion production. It is concluded that the potentiation of 3-hydroxyglutarate neurotoxicity is most probably due to an induction of astrocytic iNOS and concomitantly increased NO production, enabling enhanced peroxynitrite formation. Thus, we provide evidence for a neuroimmunological approach to the precipitation of acute encephalopathic crises in GDD by inflammatory cytokines. [source] Detection of single nucleotide substitution by competitive allele-specific short oligonucleotide hybridization (CASSOH) with immunochromatographic strip,HUMAN MUTATION, Issue 2 2003Yoichi Matsubara Abstract Recent advances in human genome research have revealed that genetic polymorphisms, such as single nucleotide polymorphisms (SNPs), are closely associated with susceptibility to various common diseases and adverse drug reactions. Also, numerous mutations responsible for a number of genetic diseases have been identified. Clinical application of genetic information to individual health care requires simple and rapid identification of nucleotide changes in clinical settings. We have devised a novel low-tech method for the detection of a single nucleotide substitution using competitive allele-specific short oligonucleotide hybridization with immunochromatographic strip. The gene of interest is PCR-amplified, hybridized to an allele-specific short oligonucleotide probe in the presence of a competitive oligonucleotide, and subjected to chromatography using a DNA test strip at room temperature. The genotype is unambiguously determined by the presence or the absence of visible purple lines on a strip. Feasibility of the method was demonstrated by the detection of a prevalent disease-causing mutations in glycogen storage disease type Ia (G6PC), medium-chain acyl-CoA dehydrogenase deficiency (ACADM), non-ketotic hyperglycinemia (GLDC), and clinically important polymorphisms in the CYP2C19 gene and the aldehyde dehydrogenase 2 gene (ALDH2). The procedure does not demand either technical expertise or expensive instruments and is readily performed in local clinical laboratories. The result is obtained within 10 min after PCR. This rapid and simple method of SNP detection may be used for point-of-care genetic diagnosis with potentially diverse clinical applications. Hum Mutat 22:166,172, 2003. © 2003 Wiley-Liss, Inc. [source] Prevalence of glucose-6-phosphate dehydrogenase deficiency in Northern GreeceINTERNAL MEDICINE JOURNAL, Issue 3 2008G. Ntaios Abstract Glucose-6-phosphate dehydrogenase (G6PD) deficiency affects more than 400 million persons worldwide. Its distribution varies significantly among different geographic regions and different population groups. Purpose of our study was to estimate its prevalence in Northern Greece. The dataset comprised 5161 newborns and adults who were screened for G6PD deficiency between July 2001 and March 2007. G6PD deficiency was detected by the dye reduction method. In the screened group, 6.3% of subjects were G6PD deficient. Moderate enzyme deficiency was shown in 139 individuals (2.7%). Complete deficiency was identified in 3.7%. The prevalence of G6PD deficiency in Northern Greece is much higher compared with the general Greek population. Moreover, G6PD prevalence in the male sex is much higher , almost double , that in the female sex. [source] Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency with inadvertent caries in infantsINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 1 2007FELIX BLAKE Background., Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare systemic disease that is associated with early tooth decay. Case report., This report describes the case of a 3-year-old boy suffering from LCHADD. At the time of referral, extensive carious lesions of the subject's maxillary dentition necessitated the surgical removal of eight teeth. Preventive treatment for LCHADD involves a regular oral intake of glucose that is vital for the survival of the affected individual. In young infants, the glucose solution needs to be administered as often as every 3 h in order to prevent hypoglycaemia, leading to a local environment similar to that experienced in nursing bottle syndrome. While nursing bottle syndrome can be resolved by eliminating the sugar substrate and curtailing the feeding sessions, these alternatives are not available in cases of LCHADD. Conclusion., This report highlights this rare disease and emphasizes its dire consequences for the dentition. Prophylactic recommendations for high-risk children are reviewed. Familiarity with LCHADD allows this high-risk group of patients to be identified, and thus, ensures diligent prophylactic action. [source] Apert syndrome with glucose-6-phosphate dehydrogenase deficiency: a case reportINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 3 2006G. TOSUN Summary., Apert syndrome is characterized by midface hypoplasia, syndactyly of the hands and feet, proptosis of eyes, steep and flat frontal bones, and premature union of cranial sutures. Maxillary hypoplasia, deep palatal vault, anterior open bite, crowding of the dental arch, severely delayed tooth eruption, and dental malocclusion are the main oral manifestations of this syndrome. In this report, a case of Apert syndrome with glucose-6-phosphate dehydrogenase (G6PD) deficiency is presented. The patient, a 4-year-old male and the fourth child of healthy parents, was admitted to our department because of delayed tooth eruption. He had all the cardinal symptoms of the Apert syndrome. Clinical examination revealed that primary centrals, canines and first molars erupted; however, primary second molars and laterals had not erupted. The patient had no dental caries. Preventive treatments were applied, and subsequently, the patient was taken to long-term follow up. [source] Impact of selected inborn errors of metabolism on prenatal and neonatal developmentIUBMB LIFE, Issue 6 2010Sabine Illsinger Abstract In general, data regarding maturational processes of different metabolic pathways in the very vulnerable fetal and neonatal period are rare. This review is to substantiate the impact of selected inborn errors of metabolism on this critical period of life and their clinical manifestation. Significant adaptation of mitochondrial/energy-, carbohydrate-, lysosomal-, and amino acid-metabolism occurs during early prenatal and neonatal development. In utero, metabolic environment has an impact on the development of the fetus as well as fetal organ maturation. Defects of distinct metabolic pathways could therefore already be of significant relevance in utero and for clinical manifestations in the early fetal and neonatal period. Disturbances of these pathways may influence intrauterine growth and health. Production of a toxic intrauterine milieu, energy-deficiency, modification of membrane function, or disturbance of the normal intrauterine expression of genes may be responsible for fetal compromise and developmental disorders. Three categories of metabolic disorders will be discussed: the "intoxication type" (classical galactosemia, ornithine transcarbamylase deficiency, and "maternal phenylketonuria"), the "storage type" (Morbus Niemann Pick type C), and the "energy deficient type" (including long-chain fatty acid oxidation disorders, pyruvate dehydrogenase deficiency, and respiratory chain defects). For these disorders, the pathophysiology of early manifestation, special aspects regarding the prenatal and neonatal period, and diagnostic as well as therapeutic options are presented. © 2010 IUBMB IUBMB Life, 62(6): 403,413, 2010 [source] Glucose-6-phosphate dehydrogenase deficiency does not result from mutations in the promoter region of the G6PD geneJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2003Panayiotis G. Menounos Abstract In this study, we investigated whether glucose-6-phosphate dehydrogenase (G6PD) promoter mutations are responsible for G6PD deficiency. We analysed the G6PD proximal promoter and the 5, untranslated region (UTR) in 65 G6PD-deficient individuals, in which no mutations have been found in the G6PD gene coding sequences, using a nonradioactive polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) analysis. We identified no sequence variations in the G6PD core promoter or in the 5, UTR of these G6PD-deficient individuals, which indicates that G6PD deficiency is not associated with promoter mutations in the G6PD locus. J. Clin. Lab. Anal. 17:90,92, 2003. © 2003 Wiley-Liss, Inc. [source] Glucose-6-phosphate dehydrogenase deficiency is associated with increased initial clinical severity of acute viral hepatitis AJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2001Israel Gotsman Abstract Background and Aim: In glucose-6-phosphate dehydrogenase (G6PD) deficiency, the enzyme is deficient in liver cells as well as in erythrocytes. It has been suggested that this may be associated with a more severe clinical presentation of acute viral hepatitis A. The aim of this study is to determine the severity of liver disease in patients with viral hepatitis and G6PD deficiency. Methods: Eighteen patients with diagnosed G6PD deficiency and acute hepatitis A were compared with 18 matched control patients with hepatitis A in a university hospital for liver disease severity and clinical outcome. Results: Two of 18 patients with G6PD deficiency had neurological deterioration. Patients with G6PD deficiency had a mean peak prothrombin time (PT) that was significantly prolonged as compared with the control group (15.5 ± 3.7 vs 12.9 ± 2.0 s, respectively, P < 0.02), and a significantly higher proportion had an abnormal PT (PT > 13.3 s): 61 versus 11% (P < 0.0001). Hemolysis occurred in 44% of the G6PD deficiency patients. Total and direct bilirubin were significantly higher in all patients with G6PD deficiency, including patients without hemolysis. There was no significant difference in liver enzyme levels between the two groups. Patients with G6PD deficiency had a longer average hospital stay (9.5 ± 4.8 vs 3.4 ± 0.8 days, respectively, P < 0.001). There was no difference in the final clinical outcome between the two groups, and recovery of liver function was seen in all patients. Conclusions: Glucose-6-phosphate dehydrogenase deficiency in patients with hepatitis A causes a more severe initial clinical presentation, but does not alter the final clinical outcome. [source] Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood,brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiencyJOURNAL OF NEUROCHEMISTRY, Issue 3 2006Sven W. Sauer Abstract Glutaric acid (GA) and 3-hydroxyglutaric acids (3-OH-GA) are key metabolites in glutaryl co-enzyme A dehydrogenase (GCDH) deficiency and are both considered to be potential neurotoxins. As cerebral concentrations of GA and 3-OH-GA have not yet been studied systematically, we investigated the tissue-specific distribution of these organic acids and glutarylcarnitine in brain, liver, skeletal and heart muscle of Gcdh -deficient mice as well as in hepatic Gcdh,/, mice and in C57Bl/6 mice following intraperitoneal loading. Furthermore, we determined the flux of GA and 3-OH-GA across the blood,brain barrier (BBB) using porcine brain microvessel endothelial cells. Concentrations of GA, 3-OH-GA and glutarylcarnitine were significantly elevated in all tissues of Gcdh,/, mice. Strikingly, cerebral concentrations of GA and 3-OH-GA were unexpectedly high, reaching similar concentrations as those found in liver. In contrast, cerebral concentrations of these organic acids remained low in hepatic Gcdh,/, mice and after intraperitoneal injection of GA and 3-OH-GA. These results suggest limited flux of GA and 3-OH-GA across the BBB, which was supported in cultured porcine brain capillary endothelial cells. In conclusion, we propose that an intracerebral de novo synthesis and subsequent trapping of GA and 3-OH-GA should be considered as a biochemical risk factor for neurodegeneration in GCDH deficiency. [source] Bilateral pulmonary edema after endoscopic sympathectomy in a patient with glucose-6-phosphate dehydrogenase deficiencyACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2001C.-J. Lan Transaxillary endoscopic sympathectomy of thoracic ganglia (T2,T3) has recently gained wider acceptance as the treatment of choice for palmar hyperhidrosis. It requires one-lung ventilation to facilitate the surgery. One-lung ventilation, however, is not without complications, among which acute pulmonary edema has been reported. In this case report, we present a patient with palmar hyperhidrosis complicated by glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, who received bilateral endoscopic sympathectomy under alternate one-lung anesthesia, and developed acute pulmonary edema immediately after recruitment of the successive collapsed lung. The effects of hypoxemia, G-6-PD deficiency and sympathectomy might all add to the development of acute pulmonary edema secondary to reexpansion of each individual lung after alternate one-lung ventilation. The possibilities of the inferred causes are herein discussed. [source] Anesthesia in pyruvate dehydrogenase deficiencyPEDIATRIC ANESTHESIA, Issue 8 2008Irina Milojevic No abstract is available for this article. [source] Anesthesia in a child with pyruvate dehydrogenase deficiencyPEDIATRIC ANESTHESIA, Issue 1 2006J.F. Mayhew No abstract is available for this article. [source] Perioperative management of a child with short-chain acyl-CoA dehydrogenase deficiencyPEDIATRIC ANESTHESIA, Issue 9 2005BRIAN TURPIN BS Summary Short-chain acyl-CoA dehydrogenase (SCAD) is a mitochondrial enzyme that catalyzes the dehydrogenation of short chain fatty acids (4 to 6 carbons in length) thereby initiating the cycle of , -oxidation. This process generates acetyl-CoA, the key substrate for hepatic ketogenesis or ATP production by the Kreb's cycle. A deficiency of SCAD results in the build-up of potentially cytotoxic metabolites including ethylmalonic acid, methylsuccinyl CoA and butyryl-carnitine. The end-organ involvement is heterogeneous, but most commonly includes hypotonia with possible lipid myopathy and developmental delay. Other reported complications include dysmorphic craniofacial features, hypoglycemia, seizures, scoliosis, hypertonia and hyperreflexia, cyclic vomiting and myocardial dysfunction. We present a 23-month-old girl with SCAD deficiency, who required posterior fossa decompression for type 1 Chiari malformation. The potential perioperative implications of SCAD deficiency are reviewed. [source] Screening for glucose-6-phosphate dehydrogenase deficiency using a modified formazan method: A pilot study on Filipino male newbornsPEDIATRICS INTERNATIONAL, Issue 1 2003CARMENCITA PADILLA AbstractBackground: Glucose-6-phosphate dehydrogenase (G6PD) deficiency has increased prevalence rates in tropical Africa, tropical and subtropical Asia and some parts of the Mediterranean. Earlier studies on G6PD deficiency in the Philippines have shown prevalence rates of 4.5% to 25.7%. Methods: In the present study, 3278 male newborns were screened for G6PD deficiency using the modified formazan method, a simple screening procedure affordable in the setting of a developing country. Subjects with positive screening results were recalled for confirmatory testing using a commercial assay kit for quantitative enzyme determination. Results: Of the 3278 boys studied, 186 revealed positive screening results. Of the 186, 65 boys had confirmatory testing. Of these 65 boys, 45 were confirmed to have G6PD deficiency and 20 had normal results. This study reveals an incidence of G6PD deficiency of 3.9% among male Filipinos. Conclusion: This study recommends the inclusion of G6PD deficiency in the panel of disorders for newborn screening among Filipino newborns. [source] Glucose-6-Phosphate Dehydrogenase Deficiency Associated Stuttering Priapism: Report of a CaseTHE JOURNAL OF SEXUAL MEDICINE, Issue 12 2008David S. Finley MD ABSTRACT Aim., Stuttering priapism is an uncommon form of recurrent priapism whose etiology if often unknown. To date, there has been one report of a patient with stuttering priapism and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Herein we describe the second-known case of recurrent priapism in a patient with G6PD deficiency. The pathophysiology of G6PD deficiency and its potential to cause priapism is reviewed. Methods., A case report is described of a 29-year-old African-American man with G6PD deficiency who presented with numerous episodes of recurrent ischemic priapism. Clinical data was reviewed. Results., Despite medical management with gonadotropin-releasing hormone (GnRH) agonist, an antiandrogen, and baclofen, he required several surgical procedures which also ultimately failed. A continuous phosphodiesterase type-5 inhibitor (PDE5) was started and the patient had no recurrences at 3-month follow-up. Conclusion., Idiopathic recurrent priapism may be explained by underlying hemolytic anemia associated with G6PD deficiency. Several possible mechanisms exist to explain this association, including hyperviscosity, direct endothelial dysfunction secondary to bare hemoglobin vasculotoxicity, and relative nitric oxide deficiency causing vasoconstriction and vascular smooth muscle proliferation. Finley DS. Glucose-6-phosphate dehydrogenase deficiency associated stuttering priapism: Report of a case. J Sex Med **;**:**,**. [source] Folinic acid,responsive seizures are identical to pyridoxine-dependent epilepsy,ANNALS OF NEUROLOGY, Issue 5 2009Renata C. Gallagher MD Objective Folinic acid,responsive seizures and pyridoxine-dependent epilepsy are two treatable causes of neonatal epileptic encephalopathy. The former is diagnosed by characteristic peaks on cerebrospinal fluid (CSF) monoamine metabolite analysis; its genetic basis has remained elusive. The latter is due to ,-aminoadipic semialdehyde (,-AASA) dehydrogenase deficiency, associated with pathogenic mutations in the ALDH7A1 (antiquitin) gene. We report two patients whose CSF showed the marker of folinic acid,responsive seizures, but who responded clinically to pyridoxine. We performed genetic and biochemical testing of samples from these patients, and seven others, to determine the relation between these two disorders. Methods CSF samples were analyzed for the presence of ,-AASA and pipecolic acid. DNA sequencing of the ALDH7A1 gene was performed. Results Both patients reported here had increased CSF ,-AASA, CSF pipecolic acid, and known or likely pathogenic mutations in the ALDH7A1 gene, consistent with ,-AASA dehydrogenase deficiency. Analysis of CSF samples from seven other anonymous individuals diagnosed with folinic acid,responsive seizures showed similar results. Interpretation These results demonstrate that folinic acid,responsive seizures are due to ,-AASA dehydrogenase deficiency and mutations in the ALDH7A1 gene. Thus, folinic acid,responsive seizures are identical to the major form of pyridoxine-dependent epilepsy. We recommend consideration of treatment with both pyridoxine and folinic acid for patients with ,-AASA dehydrogenase deficiency, and consideration of a lysine restricted diet. The evaluation of patients with neonatal epileptic encephalopathy, as well as those with later-onset seizures, should include a measurement of ,-AASA in urine to identify this likely underdiagnosed and treatable disorder. Ann Neurol 2008 [source] Murine succinate semialdehyde dehydrogenase deficiencyANNALS OF NEUROLOGY, Issue S6 2003Maneesh Gupta MBBS Inherited succinic semialdehyde dehydrogenase (SSADH) deficiency (,-hydroxybutyric aciduria) is one of the few neurogenetic disorders of GABA metabolism, and one in which tonic-clonic seizures associate with increased central nervous system GABA and ,-hydroxybutyrate (GHB). To explore pathomechanisms and develop new preclinical treatment approaches, we developed a murine knockout model of SSADH deficiency. In the absence of intervention, SSADH,/, mice suffer 100% mortality at week 3 to 4 of life from generalized tonic-clonic seizures. In this report, we summarize earlier studies indicating disruption of the GABA/glutamine axis in SSADH,/, mouse brain, effective pharmacotherapeutic approaches, preliminary gene-therapy results, and electrophysiological analyses of mutant mice. We also present new evidence for oxidative stress in SSADH,/, mice, significant alterations of dopamine metabolism, and abnormal neurosteroid levels in brain, potentially implicating the GABAA receptor in pathogenesis. In SSADH deficiency, the accumulation of two neuroactive species, GABA and GHB, is significant because GABA is one of the earliest transmitters expressed in mammals, with key roles in synaptogenesis and myelination, whereas GHB displays a vast array of pharmacological actions. The SSADH,/, mouse may represent a useful model in which to explore the effect of GABA and GHB accumulation on central nervous system development and function. Ann Neurol 2003;54 (suppl 6):S81,S90 [source] A new case of pyruvate dehydrogenase deficiency due to a novel mutation in the pdx1 geneANNALS OF NEUROLOGY, Issue 2 2003Runu Dey PhD We report a case of neonatal congenital lactic acidosis associated with pyruvate dehydrogenase E3-binding protein deficiency in a newborn girl. She had a severe encephalopathy, and magnetic resonance imaging of the brain showed large subependymal cysts and no basal ganglia lesions. She died 35 days after birth. We detected a novel homozygous deletion (620delC) in the PDX1 gene, which encodes for the E3BP subunit of the pyruvate dehydrogenase complex. [source] Unexpected glucose-6-phosphate dehydrogenase deficiencyBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2009Wing-Yan Au No abstract is available for this article. [source] Vacuolation of neutrophils and acanthocytosis in child with medium chain acyl-CoA dehydrogenase deficiencyBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2008Elodie Lainey No abstract is available for this article. [source] Drug-induced haemolysis and methaemoglobinaemia in glucose 6-phosphate dehydrogenase deficiencyBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2005Article first published online: 8 MAR 200 No abstract is available for this article. [source] Ocular characteristics in 10 children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a cross-sectional study with long-term follow-upACTA OPHTHALMOLOGICA, Issue 3 2008Kristina Teär Fahnehjelm Abstract. Purpose:, To present long-term ocular complications and electroretinographic (ERG) findings in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency , a life-threatening metabolic disease , and the relation to age at diagnosis, treatment and other clinical parameters. Methods:, Ten children with LCHAD deficiency underwent repeated ophthalmological evaluations including ERG. Results:, All 10 children developed chorioretinal pathology. Regardless of age at diagnosis, initiation of treatment and age at examination, inter-individual differences were present. Profound chorioretinal atrophy, severe visual impairment and progressive myopia had developed in two teenagers. Milder chorioretinopathy with or without subnormal visual acuity was present in all other children. ERG was pathological in seven children. The chorioretinopathy often started in the peripapillary or perimacular areas. In one patient, unilateral visual impairment was associated with fibrosis. Conclusion:, Early diagnosis and adequate therapy might delay but not prevent the progression of retinal complications. Late diagnosis with severe symptoms at diagnosis, neonatal hypoglycaemia and frequent decompensations may increase the progression rate of the chorioretinopathy. LCHAD deficiency, a potentially lethal disease, is sometimes difficult to diagnose. Unusual chorioretinal findings should alert the ophthalmologist to the long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, especially if there is a history of neonatal hypoglycaemia or failure to thrive. [source] Validation of MCADD newborn screeningCLINICAL GENETICS, Issue 2 2009EM Maier Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid ,-oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut-off policies, false-positive and negative rates. In a retrospective case-control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false-positives, and 34 patients. c.985A>G was more frequently identified in the study group and false-positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false-positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false-negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C8) and three secondary markers in the initial and follow-up sample. The new approach allowed a reduction of false-positives (by defining high cut-offs: 1.4 ,mol/l for C8; 7 for C8/C12) and false-negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42,88%) and to target NBS to MCADD-subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS-based NBS. [source] Lack of correlation between fatty acid oxidation disorders and haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome?ACTA PAEDIATRICA, Issue 1 2005M. Holub Abstract Aim: Fatty acid ,-oxidation defects comprise a heterogeneous group of disorders that may precipitate acute life threatening metabolic crises particularly during catabolic episodes. Several studies have demonstrated a possible association between fatty acid ,-oxidation defects, including long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and severe pregnancy complications. However, the precise percentage of women with haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome associated with foetal fatty acid ,-oxidation defects is not known. Methods: We carried out a multicentre retrospective study on 88 infants, born to women with HELLP syndrome. Acylcarnitine profiles from blood dried on filter paper cards were analysed by tandem mass spectrometry for the diagnosis of fatty acid ,-oxidation defects. In addition, we screened for the common long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency mutation using a standard restriction fragment length polymorphism polymerase chain reaction method. Results: None of the infants studied carried the common long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency mutation. There was no evidence of fatty acid ,-oxidation defects, including long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, as expected by unremarkable acylcarnitine profiles, while three infants with fatty acid ,-oxidation defects were diagnosed in the control group. Conclusions: Neither foetal long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, including heterozygosity for the common long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency mutation, nor fatty acid ,-oxidation defects in general are a major risk factor for HELLP syndrome in Austria. [source] | |||||||||||||||||||||||||