Carrier detection in a partially dominant X-linked disease: ornithine transcarbamylase deficiency

Hum Genet. 1990 Jan;84(2):167-71. doi: 10.1007/BF00208934.


Ornithine transcarbamylase (OTC) deficiency is an X-linked disease responsible for lethal neonatal hyperammonemia in males. Partial OTC deficiency also occurs in females and can be responsible for life-threatening hyperammonemic comas in heterozygotes (15%). Increased orotic acid excretion occurs in both symptomatic and asymptomatic carriers, especially under protein loading tests. The disease is therefore partially dominant with neonatal lethality in the hemizygous male; the fraction of new mutations has previously been estimated to be low in males (point estimation = 0, upper bound of the confidence interval = 0.16) and 57% in females. Genetic counseling in this disease is difficult because it is not clear whether a negative protein loading test rules out carrier status. In an attempt to determine how reliable the test is for carrier detection, we investigated ten obligate carriers for orotic acid excretion; considering all data available, we concluded that the test is rarely negative in obligate carriers (8%). Consequently, a negative test in a mother decreases the minimum risk of being a carrier from 84% a priori to 30% if she had an affected son and from 43% a priori to 5% if she had a heterozygous daughter. Finally, the diagnosis of a new mutation in the germ cells of the maternal grandfather in one particular family could be ascertained by extensive DNA analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Female
  • Genetic Carrier Screening*
  • Genetic Linkage*
  • Humans
  • Male
  • Mutation
  • Ornithine Carbamoyltransferase / genetics
  • Ornithine Carbamoyltransferase Deficiency Disease*
  • Orotic Acid / urine
  • Pedigree
  • X Chromosome*


  • Orotic Acid
  • Ornithine Carbamoyltransferase