RESUMO
Five patients aged 7 to 21 months are described who developed attacks of coma after a short prodromal illness with diarrhea or vomiting or both. Four had concomitant hypoglycemia, and all had hypoketonemia, with excessive urinary excretion of medium-chain dicarboxylic acids, medium-chain (omega-1)-hydroxyacids, suberylglycine, hexanoylglycine, and octanoylcarnitine. All patients accumulated octanoic acid, decanoic acid, and cis-4-decenoic acid in plasma. Fibroblasts from three patients showed a decreased rate of octanoate oxidation (10%, 12%, and 29% of control values, respectively). These findings suggest a deficiency of medium-chain acyl-CoA dehydrogenase, most probably an autosomal recessive inherited metabolic disorder. Two of the patients died during an acute attack, and a third had severe neurologic sequelae; the two remaining patients recovered. Plasma free carnitine levels were low, but total carnitine was normal. The three surviving patients underwent a fasting test, which did not lead to hypoglycemia, although hypoketonemia, dicarboxylic aciduria, and excessive mobilization of fatty acids did occur. The surviving patients were maintained on frequent carbohydrate-enriched meals.
Assuntos
Acil-CoA Desidrogenases/deficiência , Caprilatos/sangue , Carnitina/análogos & derivados , Ácidos Dicarboxílicos/urina , Ácidos Graxos/deficiência , Carnitina/urina , Células Cultivadas , Ácidos Decanoicos/sangue , Ácidos Graxos não Esterificados/sangue , Feminino , Fibroblastos/metabolismo , Humanos , Lactente , Erros Inatos do Metabolismo Lipídico/metabolismo , Masculino , OxirreduçãoRESUMO
An increasing number of reports indicate that patients with some inherited metabolic diseases may have symptoms resembling those of Reye syndrome. We describe two siblings who developed a Reye-like syndrome at ages 16 and 18 months, respectively, after a viral illness and salicylate therapy. Both had fasting hypoglycemia and hypoketonemia. At the time of the acute episode and after ingestion of a medium-chain triglyceride load, one of them excreted large amounts of abnormal metabolites derived from the omega- and (omega-1)-oxidation of medium-chain fatty acids. Medium-chain acyl-CoA dehydrogenase activity was lower than 20% of control values in fibroblasts from both patients. This enzyme defect should be considered in children with a Reye-like syndrome with these distinctive manifestations.
Assuntos
Acil-CoA Desidrogenases/genética , Síndrome de Reye/genética , Acil-CoA Desidrogenase , Acil-CoA Desidrogenases/deficiência , Acil-CoA Desidrogenases/urina , Glicemia/metabolismo , Caprilatos/sangue , Carnitina/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Feminino , Fibroblastos/enzimologia , Humanos , Lactente , Fígado/enzimologia , Fígado/patologia , Masculino , Síndrome de Reye/enzimologia , Síndrome de Reye/patologiaRESUMO
Two brothers, aged 7 and 5 years, who excreted large amounts of the leucine metabolites 3-methylglutaconic acid, 3-methylglutaric acid, and 3-hydroxyisovaleric acid, are described. The excretion of these metabolites could be enhanced by increasing the leucine intake. Restriction of the protein intake resulted in a marked reduction of the metabolite excretion. However, the excretion of the ultimate leucine metabolite, 3-hydroxy-3-methylglutaric acid, remained unchanged at a low level. The only clinical abnormality was speech retardation. A (partial) deficiency of 3-methylglutaconyl coenzyme A hydratase is proposed to be the most likely underlying defect.