Fatal initial adult-onset presentation of urea cycle defect

Arch Neurol. 2007 Dec;64(12):1777-9. doi: 10.1001/archneur.64.12.1777.


Background: Ornithine transcarbamylase (OTC) deficiency presents most commonly with neonatal hyperammonemic coma. The gene is on the X chromosome, but the disease may manifest as a dominant trait. Mutations that lead to later-onset presentations may lead to life-threatening disease and may be unrecognized, particularly when the first clinical disease occurs in adulthood.

Objective: To document the clinical and metabolic consequences of a mutation in the OTC gene.

Design: Case reports.

Setting: A metabolic/biochemical genetic referral service.

Main outcome measures: Clinical and biochemical observations in 3 generations of a family.

Results: A mutation in codon 208 of exon 6 in the OTC gene was found in a family in which the proband died of hyperammonemia at 52 years of age.

Conclusions: Diagnosis of late-onset presentations of urea cycle defect in adults may be delayed. Heightened awareness could lead to effective treatment.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Brain Edema / enzymology
  • Brain Edema / etiology
  • Brain Edema / genetics
  • DNA / genetics
  • Fatal Outcome
  • Female
  • Heterozygote
  • Humans
  • Hyperammonemia / enzymology
  • Hyperammonemia / etiology
  • Hyperammonemia / genetics
  • Infant, Newborn
  • Male
  • Metabolism, Inborn Errors / enzymology
  • Metabolism, Inborn Errors / genetics*
  • Middle Aged
  • Mutation / physiology
  • Ornithine Carbamoyltransferase / genetics*
  • Ornithine Carbamoyltransferase Deficiency Disease*
  • Pregnancy
  • Prenatal Diagnosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Twins
  • Urea / metabolism*


  • Urea
  • DNA
  • Ornithine Carbamoyltransferase