Assuntos
Agranulocitose/patologia , Quimiotaxia de Leucócito , Neutropenia/patologia , Neutrófilos/ultraestrutura , Adolescente , Medula Óssea/patologia , Núcleo Celular/ultraestrutura , Ensaio de Unidades Formadoras de Colônias , Granulócitos/imunologia , Humanos , Cariotipagem , Masculino , Monócitos/imunologia , Neutropenia/genética , Neutropenia/imunologia , PloidiasRESUMO
We have identified a patient with methylmalonic aciduria and homocystinuria due to a defect in cobalamin metabolism of the cb1C type mutant. At the time of admission at eight months of age the patient was malnourished, hypotonic and had macrocytic anemia. Neonatal screening for hypermethioninemia associated with homocystinuria had been normal. Serum vitamin B12 was markedly increased and folate concentration was above normal, as were urinary homocystine and methylmalonic acid. The patient had abnormal brain stem auditory and visual evoked potentials. Fibroblast activity of N5-methyltetrahydrofolate: homocysteine methyltransferase was reduced to approximately 10% of concurrent controls. A course of therapy with hydroxocobalamin resulted in a 90% reduction in excretion of methylmalonic acid and normalization of the evoked potentials. These studies support the efficacy of hydroxocobalamin therapy in this disease, suggest that methylmalonic acid may be the most appropriate metabolite to monitor for therapeutic response, and in importance of electrophysiologic studies in character in objectively monitoring the response to treatment metabolic disease.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Anemia Macrocítica/enzimologia , Homocistinúria/enzimologia , Malonatos/urina , Ácido Metilmalônico/urina , Vitamina B 12/sangue , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/deficiência , Dano Encefálico Crônico/enzimologia , Seguimentos , Hemoglobinometria , Humanos , Lactente , Masculino , Metilmalonil-CoA Mutase/deficiênciaRESUMO
Studies were carried out on erythrocytes and fibroblasts from a 3-year-old white male with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency and chronic non-spherocytic hemolytic anemia. Red blood cell G6PD activity was less than 0.02% of normal values. Since the child's fibroblasts had 2-4% of normal enzymic activity, they were utilized as a source of enzyme for kinetic studies. The G6PD demonstrated marked heat lability, a normal Km value for glucose-6-phosphate (56 mumol/l), a nearly normal pH-activity curve, and increased utilization of 2-deoxyglucose-6-phosphate (76% of the rate with glucose-6-phosphate). These studies clearly indicate that this is a new molecular variant (G6PD Beaumont).
