RESUMO
A 3-year-old boy had recurrent episodes of lethargy, encephalopathy, and hepatomegaly accompanied by hypoglycemia, elevated liver aminotransferase and creatine kinase values, and nonketotic dicarboxylic aciduria; the serum carnitine level was moderately reduced. Carnitine palmitoyltransferase II activity was decreased in lymphocytes and fibroblasts. Therapy with L-carnitine and a diet low in long-chain triglycerides did not prevent recurrent episodes.
Assuntos
Carnitina O-Palmitoiltransferase/deficiência , Carnitina O-Palmitoiltransferase/metabolismo , Pré-Escolar , Creatina Quinase/metabolismo , Ingestão de Energia , Ácidos Graxos/metabolismo , Humanos , Fígado/enzimologia , Linfócitos/metabolismo , Masculino , Recidiva , Transaminases/metabolismoRESUMO
A 5-year-old girl with a previous diagnosis of cerebral palsy, nonprogressive psychomotor retardation, and hypotonia was found to excrete excessive fumaric acid in urine. Fumarate hydratase activity in skin fibroblasts was 10% of the control value. This case underscores the clinical heterogeneity of neurometabolic disorders and the importance of organic acid analysis in the diagnosis of static encephalopathy.
Assuntos
Paralisia Cerebral/diagnóstico , Fumarato Hidratase/deficiência , Pré-Escolar , Erros de Diagnóstico , Feminino , Fumaratos/urina , Humanos , Deficiência Intelectual/diagnóstico , Erros Inatos do Metabolismo/diagnóstico , Hipotonia Muscular/diagnóstico , Succinatos/urina , Ácido SuccínicoRESUMO
We describe a patient with glutaryl-coenzyme A dehydrogenase deficiency, demonstrated by a residual enzyme activity of only 1% in cultured fibroblasts. Although the clinical presentation was typical of glutaric aciduria type I, the urine concentrations of glutaric, glutaconic, and 3-hydroxyglutaric acids remained normal, even during episodes of clinical decompensation. An increased free glutarate level was demonstrated only in cerebrospinal fluid.
Assuntos
Glutaratos/urina , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Oxirredutases/deficiência , Carnitina/sangue , Carnitina/urina , Diagnóstico Diferencial , Fibroblastos/enzimologia , Glutaratos/sangue , Glutaratos/líquido cefalorraquidiano , Glutaril-CoA Desidrogenase , Humanos , Lactente , Masculino , Pele/patologiaRESUMO
Two kindreds with glutaric aciduria type I were investigated. Of 20 family members who underwent neurologic examination and organic acid analysis of urine, 18 had glutaryl-coenzyme A dehydrogenase (GDH) activity determined in cultured skin fibroblasts and 12 had computed tomographic brain scans. Six homozygotes were identified who had undetectable GDH activity and identical biochemical profiles (consisting of glutaric and 3-hydroxyglutaric aciduria, reduced serum carnitine concentrations, and frontotemporal atrophy). Serial computed tomographic brain scans of one homozygous infant demonstrated the sequential postnatal development of this atrophy during 3 years before the development of clinical manifestations. In three of the six homozygotes, including the father in one kindred, there were no clinical manifestations of glutaric aciduria type I. These findings raise questions about the value of prenatal diagnosis in predicting clinical manifestations in homozygous newborn infants.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Glutaratos/urina , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Oxirredutases/deficiência , Adulto , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico por imagem , Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Encéfalo/diagnóstico por imagem , Carnitina/sangue , Carnitina/uso terapêutico , Criança , Pré-Escolar , Feminino , Fibroblastos/enzimologia , Glutaril-CoA Desidrogenase , Humanos , Lactente , Recém-Nascido , Masculino , Oxirredutases/análise , Linhagem , Pele/enzimologia , Tomografia Computadorizada por Raios XRESUMO
The autosomal recessive inherited disorder glutaryl-CoA dehydrogenase deficiency (glutaric aciduria) runs a progressive course with severe choreoathetosis and dystonia, eventually leading to total helplessness and early death. Theree patients were observed during therapeutic trials with a protein-low diet, riboflavin and GABA analogue. Diet and riboflavin had a slight-to-moderate effect on the clinical symptoms; the excretion of glutaric acid and 2-amino-adipic acid decreased considerably during treatment. Regression of neurologic symptoms was observed during treatment with GABA analogue. It is concluded that the patients should be treated as early as possible with protein-low diet, riboflavin, and GABA analogue.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/terapia , Aminobutiratos/uso terapêutico , Baclofeno/uso terapêutico , Glutaratos/urina , Oxirredutases/metabolismo , Riboflavina/uso terapêutico , Ácido 2-Aminoadípico/urina , Erros Inatos do Metabolismo dos Aminoácidos/dietoterapia , Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Criança , Dietoterapia , Proteínas Alimentares/uso terapêutico , Feminino , Humanos , Lisina/metabolismo , Masculino , Triptofano/metabolismoRESUMO
In two siblings with dystonic cerebral palsy the urinary metabolic profiles of organic acids were dominated by glutaric acid, a metabolite not normally present in urine. The exretion of glutaric acid amounted to several grams per day. The urinary excretion of beta-OH-glutaric acid and glutaconic acid was also enhanced. Imparied metabolism of glutaryl-CoA by leukocytes indicates that the patients suffer from an inborn error of lysine, tryptophan, and hydroxylysine metabolism. A defective oxidation of glutaryl-CoA to crotonyl-CoA, probably due to a deficiency of glutaryl-CoA dehydrogenase, is consistent with these findings.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Paralisia Cerebral/urina , Glutaratos/urina , Oxirredutases/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/genética , Paralisia Cerebral/genética , Criança , Pré-Escolar , Coenzima A/metabolismo , Consanguinidade , Humanos , Hidroxilisina/metabolismo , Lactente , Recém-Nascido , Lisina/metabolismo , Masculino , Triptofano/metabolismoRESUMO
Publicado en ingles en el Bull. WHO, 13(4), 1955