Carrier detection in glutaric aciduria type I using interleukin-2-dependent cultured lymphocytes.
Cultured interleukin 2 (IL-2)-dependent leukocytes from 13 patients with glutaric aciduria type I, 12 obligate carriers, 105 family members and 31 normal controls were assayed for glutaryl-CoA dehydrogenase activity. Of the 13 affected patients, 10 (all Ojibway Indian) had residual enzyme activity (2-13% of control) and 3 patients (all non-Indian) had undetectable enzyme activity. There was partial overlap between the distribution of enzyme activity in obligate heterozygotes and in normal controls (mean values +/- SD: 6.29 +/- 0.94 and 10.75 +/- 2.58 nmol/h per mg protein respectively). Using an arbitrary cutoff level of < 7 nmol/h per mg protein as presumptive evidence of carrier status, the observed frequency of carriers did not differ significantly from that expected from their a priori risk of carrier status. Thirteen per cent of the family members had inconclusive status (activity between 7 and 8.5 nmol/h per mg protein). The method appears suitable for carrier detection, although definitive carrier assignment awaits identification of the mutation(s) responsible for glutaric aciduria type I.
Seargeant
L E
LE
Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Canada.
Chudley
A E
AE
Dilling
L A
LA
Mallory
C J
CJ
Haworth
J C
JC
D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics* / Q000652:urine; D002478:Cells, Cultured; D005977:Glutarates / Q000378:metabolism*; D050770:Glutaryl-CoA Dehydrogenase; D006579:Heterozygote; D006801:Humans; D007198:Indians, North American; D007376:Interleukin-2 / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D010088:Oxidoreductases / Q000172:deficiency; D044925:Oxidoreductases Acting on CH-CH Group Donors
D005977:Glutarates; D007376:Interleukin-2; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050770:Glutaryl-CoA Dehydrogenase; C035736:glutaric acid