803 IDENTIFICATION OF HETEROZYGOSITY FOR ORNITHINE TRANSCARBAMYLASE DEFICIENCY (OTCD)

Abstract

This study was designed to determine the reliability of the protein tolerance test (PTT) in establishing heterozygosity for OTCD and hence aid in prenatal counseling and fetal diagnosis by DNA analysis in monoplex families. The results of the PTT done on 14 control women was compared to those done on 7 obligate heterozygotes. The peak urinary orotic acid (UOA) (ug orotic acid per mg creatinine) in the 14 control women varied from 0.4 to 2.0 with a mean (±SEM) peak value of 1.1. ± 0.11. The peak UOA in 7 obligate heterozygotes varied from 23.1 to 324 with a mean peak value of 179 ± 39. The absence of overlap and a p value of < .001 suggests that the PTT may be of great help in distinguishing between carriers and non-carriers of the OTCD gene. Accordingly, nine women at risk for being heterozygous for OTCD as a consequence of having borne an affected male or a symptomatic female were also studied: three of these women had UOA in the normal range (0.7, 0.98, 1.3); five had UOA in the obligate heterozygote range (20.9 to 73.5; one UOA value was ambiguous (4.9). Although these data require amplification they suggest that approximately one-third of male or female infants affected with OTCD are the result of a new mutation in a parental germ cell and that the mothers of these children are not heterozygotes. Women with ambiguous DOA values may be confirmed as carriers if a PTT done on the maternal grandmother of the affected child is unequivocally positive.