We have identified a patient with methylmalonic aciduria and homocystinuria due to a defect in cobalamin metabolism of the cbl C 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 indicate the importance of electrophysiologic studies in characterizing and in objectively monitoring the response to treatment of this metabolic disease.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Clinical Neurology