ABSTRACT

Patients with impaired synthesis of methylcobalamin and deoxyadenosylcobalamin fall into distinct complementation groups designated cobalamin (Cbl) C and Cbl D. Patients with methylmalonic aciduria and homocystinuria have defective metabolism of cobalamin to both cofactors, methylcobalamin and deoxyadenoxylcobalamin. Patients with onset later than the months of life have had predominantly neurologic presentations. Normal findings were observed in 19 per cent of patients. Hydrocephalus occurred only in the infantile onset patients. Association with vasculopathy and mitochondrial electron transport chain dysfunction has also been observed. Late onset patients in general have had better survival, responded to treatment, and had fewer neurologic sequelae than onset patients. Patients with Cbl G deficiency, like those with Cbl C, have megaloblastic anemia and neurologic abnormalities with undetectable activity of methionine synthase. The possibility that mutation in the methylenetetrahydrofolate reductase gene might act as a genetic modifier in Cbl C patients was explored and found not to affect age of onset, clinical phenotype, or outcome.