Inherited 3-methylglutaconic aciduria in two brothers--another defect of leucine metabolism.
Two brothers, aged 7 and 5 years, who excreted large amounts of the leucine metabolites 3-methylglutaconic acid, 3-methylglutaric acid, and 3-hydroxyisovaleric acid, are described. The excretion of these metabolites could be enhanced by increasing the leucine intake. Restriction of the protein intake resulted in a marked reduction of the metabolite excretion. However, the excretion of the ultimate leucine metabolite, 3-hydroxy-3-methylglutaric acid, remained unchanged at a low level. The only clinical abnormality was speech retardation. A (partial) deficiency of 3-methylglutaconyl coenzyme A hydratase is proposed to be the most likely underlying defect.
D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D005977:Glutarates / Q000652:urine*; D006801:Humans; D006836:Hydro-Lyases / Q000172:deficiency; D007930:Leucine / Q000378:metabolism*; D008297:Male; D015093:Meglutol / Q000031:analogs & derivatives / Q000652:urine; D013064:Speech Disorders / Q000235:genetics; D014631:Valerates / Q000652:urine
D005977:Glutarates; D014631:Valerates; C004961:beta-hydroxyisovaleric acid; C033686:3-methylglutaric acid; C022034:3-methylglutaconic acid; D015093:Meglutol; D006836:Hydro-Lyases; C035867:methylglutaconyl-CoA hydratase; D007930:Leucine