D-2-hydroxyglutaric aciduria and glutaric aciduria type 1 in siblings: coincidence, or linked disorders?
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.
Korman
S H
SH
Department of Clinical Biochemistry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. korman@hadassah.org.il
Salomons
G S
GS
Gutman
A
A
Brooks
R
R
Jakobs
C
C
D020739:Brain Diseases, Metabolic, Inborn / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D002675:Child, Preschool; D005260:Female; D005977:Glutarates / Q000097:blood / Q000652:urine*; D050770:Glutaryl-CoA Dehydrogenase; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency / Q000235:genetics; D035781:Siblings
D005977:Glutarates; C019417:alpha-hydroxyglutarate; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050770:Glutaryl-CoA Dehydrogenase; C035736:glutaric acid