Methylmalonic Aciduria

An eight-month-old boy was seen with profound metabolic acidosis, developmental retardation and a very unusual biochemical triad: methylmalonic aciduria; long chain ketonuria; and intermittent hyperglycinemia. Ingestion of a diet high in protein or one with a moderate amount of protein supplemented with valine or isoleucine accentuated the methylmalonic aciduria and precipitated ketoacidosis and long-chain ketonuria. There was no temporal association between these clinical and biochemical abnormalities and the elevated plasma glycine concentrations. The findings suggest that the methylmalonic aciduria, acidosis and ketonuria are the result of an inborn enzymatic defect in the conversion of methylmalonyl coenzyme A to succinyl coenzyme A. These studies also demonstrate that methylmalonic aciduria and idiopathic hyperglycinemia are two distinct but very closely related disorders.