Methylmalonic aciduria: a variant form of methylmalonyl coenzyme A apomutase deficiency.

Sisters aged 3 and 4 1/2 years, respectively, who had grown and developed normally were found to have methylmalonic aciduria. The elder had had only one previous illness, at 18 months, and was thriving at six years without treatment; she was excreting up to 2 gm methylmalonic acid per day. The younger sister died during her third episode of illness, at 3 years of age. Studies of cultured skin fibroblasts showed deficient methylmalonyl coenzyme A mutase apoenzyme activity; cobalamin metabolism was normal. There was a moderate response in cultured cells to large amounts of added hydroxycobalamin; but treatment of the patient with high doses of intramuscular vitamin B12 for ten days failed to lower the urinary excretion of methylmalonic acid.