Clinical heterogeneity in cobalamin C variant of combined homocystinuria and methylmalonic aciduria

We describe two patients with methylmalonic aciduria and homocystinuria (Cbl C). The disorder was not diagnosed in patient 1 until 41/2 years of age; he had a history of fatigue, anorexia, delirium, and spasticify. Moderate megaloblastic bone marrow changes were observed, and there was hyperreftexia of the lower limbs. His condition improved clinically with hydroxycobalamin therapy. Patient 2 was hospitalized at 6 weeks of age because of lethargy and poor feeding. She was found to have macrocytosis. Despite an initial good clinical response to hydroxycobalamin, she developed a striking pigmentary retinopathy. Methylmalonic aciduria persisted in both patients, and homocystinuria persisted in patient 1 despite therapy. The diagnosis of CbI C disease has been confirmed in both patients by biochemical studies of cultured fibroblasts, including complementation studies. The differences in age of onset and clinical findings together with the similar biochemical findings in these two patients demonstrate the heterogeneity of phenotypic expression in patients with apparently identical abnormalities of vitamin B 12 metabolism.