The allopurinol loading test for identification of carriers for ornithine carbamoyl transferase deficiency: studies in a healthy control population and females at risk.

The increase in orotidine excretion following a 300 mg allopurinol dose has been used for carrier detection in ornithine carbamoyl transferase (OCT) deficiency. This test was evaluated, using three collection periods, in 23 healthy women, 4 obligate heterozygotes and 32 other women at risk of being carriers of OCT deficiency. Four methods for the analysis of orotidine and orotic acid were compared. Using the most reproducible method, the excretion of orotic acid in controls was found to be consistently higher than that of orotidine in all three periods. The distribution of both orotic acid and orotidine excretion of controls was skewed so that standard deviations (S.D.) were calculated after logarithmic transformation. All four obligate heterozygotes showed orotic acid and orotidine excretion in excess of 3 S.D. above the control mean and a further 7 women had one or more excretion values in excess of 3 S.D., while 16 gave a value of less than 2 S.D. for both metabolites. We conclude that the predictive value of the test is good, that both orotic acid and orotidine should be measured to reduce the risk of misclassification and that values greater than 2 S.D. for both in one or more periods should be used as the cut-off point to identify carriers.