D-2-hydroxyglutaric aciduria and glutaric aciduria type 1 in siblings: coincidence, or linked disorders?

Neuropediatrics. 2004 Jun;35(3):151-6. doi: 10.1055/s-2004-817905.


Glutaric aciduria type 1 (GA1) and D-2-hydroxyglutaric aciduria ( D-2-HGA) are cerebral organic acidurias characterized by the excretion of 3-hydroxyglutaric and D-2-hydroxyglutaric acids, respectively. GA1 is caused by a deficiency of glutaryl-CoA dehydrogenase encoded by the GCDH gene; the biochemical and genetic basis of D-2-HGA is unknown. We diagnosed GA1 in the son of consanguineous Palestinian parents, and D-2-HGA in his sister and brother. All three siblings were neurologically and developmentally normal. A small but abnormal increase in excretion of D-2-hydroxyglutaric acid was also found in the sibling with GA1. These observations suggested a possible pathophysiological link between these two disorders. The sibling with GA1 was homozygous whilst his siblings with D-2-HGA were heterozygous for a 1283 C>T missense mutation (T416I) in exon 11 of the GCDH gene. However, sequence analysis of the GCDH gene in 8 additional unrelated patients with D-2-HGA and 3 with combined D/ L-2-HGA did not reveal any pathogenic mutations. The biochemical and genetic basis of D-2-HGA remains to be determined.

MeSH terms

  • Brain Diseases, Metabolic, Inborn / diagnosis
  • Brain Diseases, Metabolic, Inborn / genetics*
  • Brain Diseases, Metabolic, Inborn / metabolism*
  • Child, Preschool
  • Female
  • Glutarates / blood
  • Glutarates / urine*
  • Glutaryl-CoA Dehydrogenase
  • Humans
  • Infant, Newborn
  • Male
  • Mutation
  • Oxidoreductases Acting on CH-CH Group Donors / deficiency
  • Oxidoreductases Acting on CH-CH Group Donors / genetics
  • Siblings


  • Glutarates
  • alpha-hydroxyglutarate
  • Oxidoreductases Acting on CH-CH Group Donors
  • Glutaryl-CoA Dehydrogenase
  • glutaric acid