RESUMO
A 5-year-old boy of West African origin had methylmalonic acidemia with a mut- enzyme phenotype, no clinical response to hydroxycobalamin, and metabolite measurements indicative of the severe form of mutase deficiency. His development, both mental and physical, was satisfactory and he had no episodes of metabolic decompensation. The explanation for the neurotoxic effects and metabolic decompensation in typical methylmalonic acidemia and the (allelic) genotype that explains this patient's phenotype are uncertain.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/urina , Ácido Metilmalônico/urina , Pré-Escolar , Genótipo , Humanos , Masculino , FenótipoRESUMO
Monozygotic male twins born to nonconsanguineous parents had dysmorphic facial features, microcephaly, migrational brain disorder, and congenital intracerebral calcification. They excreted excessive amounts of 3-hydroxyisobutyric acid, a metabolite of valine, and had evidence of impaired oxidative metabolism and metabolic acidosis. The level of 3-hydroxyisobutyrate in stored samples of midtrimester amniotic fluid was found to be high. The association of 3-hydroxyisobutyric aciduria with brain dysgenesis is a newly recognized mendelian disorder; its recurrence in a family at risk is potentially avoidable by prenatal diagnosis.
Assuntos
Encefalopatias/congênito , Encéfalo/anormalidades , Calcinose/congênito , Doenças em Gêmeos , Hidroxibutiratos/urina , Gêmeos Monozigóticos , Líquido Amniótico/química , Encefalopatias/genética , Calcinose/genética , Citogenética , Impressões Digitais de DNA , Humanos , Hidroxibutiratos/análise , Recém-Nascido , Masculino , Erros Inatos do Metabolismo/genética , Reação em Cadeia da PolimeraseRESUMO
A female child presented at one year of age with a febrile illness and loose stools, then developed severe ketoacidosis with vomiting; an apparent salicylate level of 11 mg/dl was measured. A sibling had died in similar circumstances nine years earlier. Investigation revealed that the child did not have salicylate intoxication, and that high levels of acetoacetate in blood and urine were giving readings indicative of the presence of salicylate on routine testing. Gas-liquid chromatographic analysis combined with mass spectrometry on urine samples revealed the presence of 2-methyl-acetoacetate, 2-methyl-3-hydroxybutyrate, and tiglyl glycine in appreciable amounts, indicating a defect in isoleucine catabolism located at the beta-ketothiolase step. The oxidation of 14C-isoleucine to CO2 in cultured fibroblasts confirmed that this pathway was defective. We present evidence that beta-ketothiolase deficiency is not simply a defect of isoleucine degradation; the deficient enzyme is the K+ dependent short-chain mitochondrial thiolase, which also plays a major catalytic role in ketone body and fatty acid oxidation.