3-Hydroxy-3-methylglutaric aciduria: response to carnitine therapy and fat and leucine restriction.

A female infant, born to first cousin parents, lapsed into coma with severe metabolic acidosis on day three of life. The gas chromatographic/mass spectrometric urinary organic acid profile showed marked elevation of the leucine metabolites 3-hydroxy-3-methylglutaric, 3-methylglutaconic, 3-methylglutaric and 3-hydroxy-isovaleric acids. Less than 5% of the normal activity of the enzyme 3-hydroxy-3-methylglutaryl CoA lyase was detected in cultured skin fibroblasts. The patient's total and free carnitine was initially low but rose to normal levels after placing her on DL-carnitine (100 mg kg-1 d-1). On a diet providing 87 mg kg-1 d-1 of leucine and only 25% of total calories as fat and 2 g kg-1 d-1 protein, the concentration of the urinary organic acids fell markedly. She is now 15 months old with normal growth and development. This regimen appears effective in the early treatment of 3-hydroxy-3-methylglutaric aciduria.