3-Methylglutaconic aciduria type I is caused by mutations in AUH

Am J Hum Genet. 2002 Dec;71(6):1463-6. doi: 10.1086/344712. Epub 2002 Nov 14.


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.

MeSH terms

  • Acyl Coenzyme A / metabolism
  • DNA Mutational Analysis
  • Enoyl-CoA Hydratase / metabolism
  • Fibroblasts
  • Genes, Recessive / genetics
  • Humans
  • Hydro-Lyases / deficiency
  • Hydro-Lyases / genetics*
  • Hydro-Lyases / metabolism
  • Language Development Disorders / complications
  • Language Development Disorders / enzymology*
  • Language Development Disorders / genetics*
  • Molecular Sequence Data
  • Mutation / genetics*
  • Nervous System Diseases / complications
  • Nervous System Diseases / enzymology*
  • Nervous System Diseases / genetics*


  • Acyl Coenzyme A
  • 3-hydroxy-3-methylglutaryl-coenzyme A
  • Hydro-Lyases
  • Enoyl-CoA Hydratase
  • methylglutaconyl-CoA hydratase

Associated data

  • OMIM/250950
  • OMIM/250951
  • OMIM/258501
  • OMIM/302060
  • OMIM/600890
  • RefSeq/NM_001698
  • RefSeq/NT_008476