RESUMO
An 8-year-old boy is described with borderline cognitive impairment, cerebellar hypoplasia, a stroke-like episode, and venous thrombosis of the left leg after a period of immobilization. The pattern of multiple abnormalities in blood coagulation suggested carbohydrate-deficient glycoprotein syndrome type 1a. Isoelectric focusing of serum transferrin was abnormal. The activity of phosphomannomutase in leukocytes and fibroblasts was decreased. Mutation analysis of the PMM2 gene revealed the R141H/E151G genotype. These results confirm the presence of carbohydrate-deficient glycoprotein syndrome type 1a without severe psychomotor retardation.
Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Cerebelo/anormalidades , Transtornos Cognitivos/diagnóstico , Defeitos Congênitos da Glicosilação/diagnóstico , Criança , Defeitos Congênitos da Glicosilação/classificação , Defeitos Congênitos da Glicosilação/genética , Humanos , Masculino , Fenótipo , Fosfoglucomutase/genética , Fosfotransferases (Fosfomutases)/genéticaAssuntos
Cardiomiopatia Dilatada/genética , Ligação Genética/genética , Glutaratos/urina , Transtornos do Crescimento/genética , Miopatias Mitocondriais/genética , Neutropenia/genética , Cromossomo X/genética , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/metabolismo , Criança , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/metabolismo , Humanos , Masculino , Miopatias Mitocondriais/diagnóstico , Miopatias Mitocondriais/metabolismo , Mutação/genética , Neutropenia/diagnóstico , Neutropenia/metabolismo , SíndromeRESUMO
Combined 3-methylglutaconic and 3-methylglutaric aciduria, one of the more common urinary organic acid abnormalities, has been observed in at least three clinical syndromes. We studied an additional seven patients with 3-methylglutaconic aciduria, four of whom were best categorized as having the type II syndrome, two as having an "unspecified" syndrome, and one who may have had a primary urea cycle defect. In cultured cells and autopsy tissues derived from patients with the type II and unspecified syndromes, we were unsuccessful in identifying a defect in the leucine degradative pathway distal to 3-methylcrotonyl-coenzyme A carboxylase and in the cholesterol biosynthetic pathway between 3-hydroxy-3-methylglutaryl-coenzyme A reductase and diphosphomevalonate decarboxylase. Further assessment of the cholesterol biosynthetic pathway in several patients with one of the two types of disease also provided no defined abnormality. The primary metabolic defects in the type II and unspecified syndromes remain undefined.