title: 3-Methylglutaconic aciduria in two infants.
abstract: We studied two children who developed normally for the first 3-4 months of life and then displayed a failure-to-thrive syndrome, regression in psychomotor development, pronounced muscular hypotonia, and liver damage. At the age of about 1-2 years, optic atrophy and spastic parapareses were evident. One child died at the age of 2.5 years the other at an age of 4 years. Both children excreted 3-methylglutaconic acid, 0.1-0.4 mol/mol creatinine and 3-methylglutaric acid, 0.02-0.05 mol/mol creatinine. The excretion of 3-hydroxy-3-methylglutaric acid was not increased. One of the children was available for further biochemical studies. The activity of hydroxymethylglutaryl-CoA lyase (EC 4.1.3.4) was moderately reduced in leucocytes and fibroblasts. During a 21-h fast there was a normal formation of ketone bodies and we conclude that the cause of the syndrome is not a deficiency of hydroxymethylglutaryl-CoA lyase. Normal formation of 14CO2 from [1-14C]isovaleric acid and [2-14C]leucine in fibroblasts and leucocytes apparently excludes a deficiency of methylglutaconyl CoA-hydratase (EC 4.2.1.18).
mesh_terms: D003404:Creatinine / Q000097:blood; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005977:Glutarates / Q000652:urine*; D045782:Hemiterpenes; D006801:Humans; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000378:metabolism; D007223:Infant; D007930:Leucine / Q000378:metabolism; D007962:Leukocytes / Q000201:enzymology; D015093:Meglutol / Q000031:analogs & derivatives / Q000652:urine; D008661:Metabolism, Inborn Errors / Q000378:metabolism*; D010421:Pentanoic Acids / Q000378:metabolism
chemical_list: D005977:Glutarates; D045782:Hemiterpenes; D010421:Pentanoic Acids; C008216:isovaleric acid; C033686:3-methylglutaric acid; C022034:3-methylglutaconic acid; D003404:Creatinine; D015093:Meglutol; D006904:Hydroxymethylglutaryl-CoA Synthase; D007930:Leucine