Glutaryl-CoA dehydrogenase deficiency presenting as 3-hydroxyglutaric aciduria

Two siblings who were found to have deficiency of glutaryl-CoA dehydrogenas e were identified by the presence of large amounts of 3-hydroxyglutaric aci d in the urine, Patients with this disease, termed glutaric acidemia or glu taric acidemia Type I, usually present with large amounts of glutaric acid in the urine, and amounts of 3-hydroxyglutaric acid found are less. Patient s were ataxic and dystonic, Intelligence was normal, 3-Hydroxyglutaric acid in the urine was quantified by organic acid analysis via gas chromatograph y mass spectrometry (GCMS) and by stable isotope-dilution (internal standar d) GCMS. Glutaryl-CoA dehydrogenase activity in cultured fibroblasts was fo und to be 2% of the control level, The nature of the mutations was identifi ed, and both patients were found to be compound heterozygotes for R227P, wh ich changed an arginine to a proline, and E365K, which changed a glutamate to a lysine. (C) 1999 Academic Press.