Methylmalonic acidaemia due to mutase apoenzyme defect: responsive to vitamin B12 in intact fibroblasts but not in vivo.

Congenital methylmalonic acidaemia (MMA-aemia) was diagnosed in an 8-month-old girl who presented with severe metabolic acidosis, hypoglycaemia and hyperglycinaemia. Vomiting, failure to thrive and apathy first appeared when breast feeding was replaced by a cows' milk formula at the age of 3 months. The patient, unresponsive to OH-Cbl therapy, was successfully treated with dietary protein restriction and with Shohl's solution. Aged 4 years 9 months, she is in good health. Studies in cultured fibroblasts revealed a defect of the MMA-CoA mutase apoenzyme. Mutase activity in cell extracts was barely detectable both with and without added coenzyme (Ado-Cbl). Addition of OH-Cbl to the culture medium improved overall propionate metabolism in intact fibroblasts but had no effect on mutase activity in cell extracts. These observations point to the presence of a very labile mutant enzyme, suggesting that the patient reported here may be suffering from yet another variant of MMA-aemia.