The allopurinol loading test is commonly used to detect heterozygotes for ornithine transcarbamylase deficiency (OTCD). We have compared this diagnostic procedure with one based on the formation of plasma [15N]urea and[5-15N]glutamine during a 4 hour period following the oral administration of 15NH4 (1200 mg). Four groups were studied: (a) healthy adult controls (n=10); (b) asymptomatomatic female heterozygotes(n=25); (c) symptomatic female heterozygotes (n=14); and (d) and male hemizygotes (n=9). Measurements of urinary orotate during the 4.5 hrs following the allopurinol load did not discriminate either group of heterozygotes or hemizygotes from controls (p >.05). In contrast, the cumulative formation of plasma [15N]urea in symptomatic heterozygotes and male hemizygotes was significantly lower than in controls. Asymptomatic heterozygotes formed as much [15N]urea as did the controls. All heterozygotes, whether asymptomatic or symptomatic, as well as the male hemizygotes, formed significantly more [5-15N]glutamine than did the control group. The most sensitive discriminator of individuals with OTCD was the[5-15N]glutamine/[15N]urea ratio, the normal value for which(70.1 ± 9.1; SEM) was significantly less (p <.05) than that of either asymptomatic heterozygotes (604.2 ± 119.0), symptomatic heterozygotes (2100.3 ± 578.6) or hemizygotes (8229.6 ± 7145.8). This ratio was lower in all (100%) control subjects than in any subject affected with ornithine transcarbamylase deficiency. We conclude that: (a) the15 NH4 loading test affords an effective diagnostic procedure for the detection of individuals who have a mutation of the ornithine transcarbamylase gene; and (b) this procedure is more sensitive than the allopurinol loading test when urine orotate is measured in the first few hours after allopurinol adminstration.
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Yudkoff, M., Daikhin, Y., Paibin, C. et al. Detecting Heterozygotes for Ornithine Transcarbamylase Deficiency: Comparison of Allopurinol Loading Test With 15NH4 Loading Study† 744. Pediatr Res 43 (Suppl 4), 129 (1998). https://doi.org/10.1203/00006450-199804001-00765
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DOI: https://doi.org/10.1203/00006450-199804001-00765