Abstract
In addition to its effects on purine metabolism, AP, via its metabolite, oxipurinol ribonucleotide, inhibits pyrimidine biosynthesis (PB) at the level of orotidine mono-phosphate decarboxylase. This inhibition results in increased ODNU. Women heterozygous at the OTC locus have 2 populations of hepatocytes; OTC normal and OTC deficient. We hypothesize that, as a consequence of carbamyl phosphate accumulation in the latter cells, PB is chronically increased. Therefore, inhibition of PB by AP should result in an even greater increase in ODNU in OTCH as compared to controls. The AP test includes administration of 300mg of AP followed by four pooled consecutive 6 hr urine collections. Urinary orotidine was measured by reverse phase HPLC after isolation of nucleosides on a boronate affinity column. We studied 11 control women (C) and 12 obligate OTC heterozygotes (OTCH). The mean (±SEM) peak urine orotidine (umol/mmol creatinine) of C and OTCH was respectively 7.36±0.46 (range 5.7-10.1) and 39.7±7.3. One OTCH fell in the normal range (7.71); other OTCH values ranged from 17.9 to 97.9. Comparison of these results with a protein tolerance test (PTT) administered to the same subjects, shows that the diagnostic sensitivity of the 2 tests are the same and that the same OTCH was negative in both. We conclude that PB is chronically increased in OTCH; and that the AP test identifies OTCH as well as the PTT, eliminates the risk of hyperammonemia, and is more convenient and acceptable.
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Brusilow, S., Valle, D. ALLOPURINOL (AP) INDUCED OROTIDINURIA (ODNU): A TEST OF HETEROZYGOSITY FOR ORNITHINE TRANS-CARBAHYLASE (OTC) DEFICIENCY. Pediatr Res 21 (Suppl 4), 289 (1987). https://doi.org/10.1203/00006450-198704010-00729
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DOI: https://doi.org/10.1203/00006450-198704010-00729
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