title: 3-Methylglutaconic aciduria type I is caused by mutations in AUH.
abstract: 3-Methylglutaconic aciduria type I is an autosomal recessive disorder clinically characterized by various symptoms ranging from delayed speech development to severe neurological handicap. This disorder is caused by a deficiency of 3-methylglutaconyl-CoA hydratase, one of the key enzymes of leucine degradation. This results in elevated urinary levels of 3-methylglutaconic acid, 3-methylglutaric acid, and 3-hydroxyisovaleric acid. By heterologous expression in Escherichia coli, we show that 3-methylglutaconyl-CoA hydratase is encoded by the AUH gene, whose product had been reported elsewhere as an AU-specific RNA-binding protein. Mutation analysis of AUH in two patients revealed a nonsense mutation (R197X) and a splice-site mutation (IVS8-1G-->A), demonstrating that mutations in AUH cause 3-methylglutaconic aciduria type I.
authors.affiliation: Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Lodewijk
authors.initials: L
authors.lastname: IJlst
authors.forename: Ference J
authors.initials: FJ
authors.lastname: Loupatty
authors.forename: Jos P N
authors.initials: JP
authors.lastname: Ruiter
authors.forename: Marinus
authors.initials: M
authors.lastname: Duran
authors.forename: Willy
authors.initials: W
authors.lastname: Lehnert
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D004252:DNA Mutational Analysis; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D005347:Fibroblasts; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D006836:Hydro-Lyases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D007805:Language Development Disorders / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009422:Nervous System Diseases / Q000150:complications / Q000201:enzymology* / Q000235:genetics*
chemical_list: D000214:Acyl Coenzyme A; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D006836:Hydro-Lyases; D004746:Enoyl-CoA Hydratase; C035867:methylglutaconyl-CoA hydratase