Clinical and biochemical heterogeneity in females of a large pedigree with ornithine transcarbamylase deficiency due to the R141Q mutation

Mary J. Ahrens, Susan A. Berry, Chester B. Whitley, Dorothy J. Markowitz, Robert J. Plante, Mendel Tuchman

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14 Scopus citations

Abstract

A large family with ornithine transcarbamylase deficiency due to mutation R141Q was ascertained through a propositus who presented with acute neonatal hyperammonemic coma. Of 13 females at risk, 11 were evaluated clinically and had laboratory studies performed. Seven were found to be heterozygous for the mutation. Of these seven, five had chronic clinical symptoms and two were asymptomatic. None of the heterozygotes had elevated plasma ammonia on random testing. Of the five symptomatic females, three had markedly elevated plasma glutamine levels on random testing, while two had levels in the upper range of normal. Plasma citrulline and arginine levels were somewhat lower in the symptomatic individuals but still within the normal range. Five heterozygotes who were tested had either spontaneous orotic aciduria or elevated orotic acid following ingestion of allopurinol, whereas one unaffected female and one unaffected male had normal allopurinol tests. A higher than expected proportion of female heterozygous for the R141Q mutation were clinically and biochemically symptomatic but remained undiagnosed for many years. Plasma glutamine determination and allopurinol testing should be performed in females who present with a combination of relatively non-specific symptoms detailed in this report.

Original languageEnglish (US)
Pages (from-to)311-315
Number of pages5
JournalAmerican Journal of Medical Genetics
Volume66
Issue number3
DOIs
StatePublished - Dec 18 1996

Keywords

  • X-linked heterozygosity
  • clinical heterogeneity
  • hyperammonemia
  • ornithine transcarbamylase deficiency
  • ornithine transcarbamylase gene
  • urea cycle

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