Methylmalonic aciduria. An inborn error of metabolism leading to chronic metabolic acidosis.

Although metabolic acidosis from a variety of causes is very frequent in infancy, congenital acidosis appears to be extremely rare. Two unrelated cases of a new syndrome are now described with a congenital metabolic acidosis resulting from a block in the conversion of methylmalonic acid to succinic acid. The first had persistent mild acidosis with acute episodes of severe metabolic acidosis during the first year of life. He was thought to have renal tubular acidosis, albeit atypical, and died during an acute episode at 2 years of age in 1959. His disorder was always considered to have been similar to that of the later case, and this was confirmed 7 years after death by an examination of his stored plasma. The second child, born in 1960, had persistent acidosis with acute exacerbations from the first week of life. She was found to have renal tubular acidosis, confirmed by the hydrogen ion clearance index, and treatment with alkalis was instituted, but her course was atypical. In one severe episode of acidosis it was noted that she was excreting a very acid urine during treatment, in spite of a normal blood pH and plasma bicarbonate. An analysis of the urine for organic acids revealed that she was excreting large amounts of methylmalonic acid, an intermediate in the metabolism of some amino acids and of fatty acids with an odd number of carbon atoms. The effect of the metabolic block on protein and carbohydrate metabolism has also been studied, and preliminary investigations to elucidate the metabolic defect are presented.