title: 3-Hydroxy-3-methylglutaric aciduria: response to carnitine therapy and fat and leucine restriction.
abstract: 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.
mesh_terms: D000138:Acidosis / Q000209:etiology; D000592:Amino Acid Metabolism, Inborn Errors / Q000178:diet therapy / Q000188:drug therapy* / Q000652:urine; D002331:Carnitine / Q000172:deficiency / Q000627:therapeutic use*; D004041:Dietary Fats / Q000008:administration & dosage; D004044:Dietary Proteins / Q000008:administration & dosage; D005260:Female; D005977:Glutarates / Q000652:urine*; D006801:Humans; D007231:Infant, Newborn; D007930:Leucine / Q000008:administration & dosage; D015093:Meglutol / Q000652:urine*; D007652:Oxo-Acid-Lyases / Q000172:deficiency*
chemical_list: D004041:Dietary Fats; D004044:Dietary Proteins; D005977:Glutarates; D015093:Meglutol; D007652:Oxo-Acid-Lyases; C021410:3-hydroxy-3-methylglutaryl-coenzyme A lyase; D007930:Leucine; D002331:Carnitine