Risk of serious illness in heterozygotes for ornithine transcarbamylase deficiency

J Pediatr. 1986 Feb;108(2):236-41. doi: 10.1016/s0022-3476(86)80989-1.


Ornithine transcarbamylase (OTC) deficiency is an X-linked disorder associated with hyperammonemia. Heterozygous females have variable clinical expression, ranging from asymptomatic illness to recurrent episodes of hyperammonemic coma. We studied 17 OTC-deficient kindreds containing 114 women at risk for heterozygosity. Sixty-one of these women were designated heterozygotes by pedigree analysis, history of protein intolerance, protein tolerance tests, or DNA probe studies. Eleven (18%) of the 61 heterozygotes had experienced encephalopathic episodes; nine (82%) girls died during these episodes. Our findings indicate that there is a significant risk of symptomatic hyperammonemia in females heterozygous for OTC deficiency. We suggest that, within OTC-deficient kindreds, females at risk should be identified early, by means of protein tolerance tests and DNA probe studies. Those who develop significant hyperammonemia after a protein load should be considered for long-term alternate pathway therapy and should receive aggressive therapy during hyperammonemic episodes.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / complications
  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Ammonia / blood*
  • Child, Preschool
  • Coma / etiology
  • Female
  • Genetic Carrier Screening
  • Genetic Linkage
  • Heterozygote*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Ornithine Carbamoyltransferase Deficiency Disease*
  • Pedigree
  • Risk
  • X Chromosome


  • Ammonia