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Allopurinol-induced orotidinuria. A test for mutations at the ornithine carbamoyltransferase locus in women.

Publication ,  Journal Article
Hauser, ER; Finkelstein, JE; Valle, D; Brusilow, SW
Published in: N Engl J Med
June 7, 1990

Ornithine carbamoyltransferase is an X-linked mitochondrial enzyme expressed in hepatocytes and enterocytes. A deficiency of this enzyme results in central nervous system dysfunction, which may be fatal in newborn boys. Milder forms are seen in older boys and girls and in adults. Establishing the carrier status of women at risk for ornithine carbamoyltransferase deficiency is important for determining reproductive and medical risks for affected women. We report a test to establish the carrier status of women at risk for ornithine carbamoyltransferase deficiency. This test relies on the allopurinol-induced accumulation of orotidine, whose synthesis is stimulated by carbamoyl phosphate, a substrate that accumulates in ornithine carbamoyltransferase deficiency. We used anion-exchange, high-performance liquid chromatography to measure urinary orotidine and orotic acid excretion after the administration of a 300-mg oral dose of allopurinol in 25 [corrected] women who were obligate heterozygotes, 13 who were probable heterozygotes, 15 mothers of affected boys from monoplex families (families with only one affected member), 12 mothers of affected girls from monoplex families, and 21 [corrected] normal, unrelated women who were not carriers. Urinary orotidine excretion was increased 3 SD or more above the mean value for the normal women in 95.8 percent of the obligate heterozygotes, 84.6 percent of the probable heterozygotes, 73.3 percent of the mothers of affected boys in monoplex families, and 33.3 percent of the mothers of affected girls in monoplex families, thus establishing that these women were carriers of a mutant ornithine carbamoyltransferase allele. The presence of allopurinol-induced orotic aciduria was not as sensitive or specific an indicator of carrier status as the presence of orotidinuria. We conclude that measurement of urinary orotidine excretion after the administration of allopurinol is a simple and reliable test for the identification of women who are heterozygous for ornithine carbamoyltransferase deficiency.

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Published In

N Engl J Med

DOI

ISSN

0028-4793

Publication Date

June 7, 1990

Volume

322

Issue

23

Start / End Page

1641 / 1645

Location

United States

Related Subject Headings

  • Uridine
  • Orotic Acid
  • Ornithine Carbamoyltransferase Deficiency Disease
  • Ornithine Carbamoyltransferase
  • Middle Aged
  • Humans
  • Heterozygote
  • Genetic Carrier Screening
  • General & Internal Medicine
  • Female
 

Citation

APA
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ICMJE
MLA
NLM
Hauser, E. R., Finkelstein, J. E., Valle, D., & Brusilow, S. W. (1990). Allopurinol-induced orotidinuria. A test for mutations at the ornithine carbamoyltransferase locus in women. N Engl J Med, 322(23), 1641–1645. https://doi.org/10.1056/NEJM199006073222305
Hauser, E. R., J. E. Finkelstein, D. Valle, and S. W. Brusilow. “Allopurinol-induced orotidinuria. A test for mutations at the ornithine carbamoyltransferase locus in women.N Engl J Med 322, no. 23 (June 7, 1990): 1641–45. https://doi.org/10.1056/NEJM199006073222305.
Hauser ER, Finkelstein JE, Valle D, Brusilow SW. Allopurinol-induced orotidinuria. A test for mutations at the ornithine carbamoyltransferase locus in women. N Engl J Med. 1990 Jun 7;322(23):1641–5.
Hauser, E. R., et al. “Allopurinol-induced orotidinuria. A test for mutations at the ornithine carbamoyltransferase locus in women.N Engl J Med, vol. 322, no. 23, June 1990, pp. 1641–45. Pubmed, doi:10.1056/NEJM199006073222305.
Hauser ER, Finkelstein JE, Valle D, Brusilow SW. Allopurinol-induced orotidinuria. A test for mutations at the ornithine carbamoyltransferase locus in women. N Engl J Med. 1990 Jun 7;322(23):1641–1645.
Journal cover image

Published In

N Engl J Med

DOI

ISSN

0028-4793

Publication Date

June 7, 1990

Volume

322

Issue

23

Start / End Page

1641 / 1645

Location

United States

Related Subject Headings

  • Uridine
  • Orotic Acid
  • Ornithine Carbamoyltransferase Deficiency Disease
  • Ornithine Carbamoyltransferase
  • Middle Aged
  • Humans
  • Heterozygote
  • Genetic Carrier Screening
  • General & Internal Medicine
  • Female