Isovaleric acidemia: a new genetic defect of leucine metabolism.

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Abstract
A new genetic defect of leucine metabolism is described where there is a marked accumulation of isovaleric acid, a catabolite of leucine. Two siblings with this hereditary disease have an intolerance to protein and to develop recurrent episodes of metabolic acidosis, with stupor or coma. They have mild mental retardation and an unusual body odor which is due to the elevated levels of isovaleric acid in their body fluids. When these children were given oral leucine, the blood isovaleric acid levels increased greatly and neurologic changes developed. The metabolism of 1-C14-isovaleric acid to C14O2 by white blood cells of these patients was markedly impaired. The metabolic block in this disorder may be in the conversion of isovaleryl CoA to [beta]-methylcrotonyl CoA.