Metabolic and neuropsychological phenotype in women heterozygous for ornithine transcarbamylase deficiency

Ann Neurol. 2004 Jan;55(1):80-6. doi: 10.1002/ana.10794.


We compared neurocognitive indices with clinical status, mutation analysis, and urea synthetic capacity in 19 women heterozygous for ornithine transcarbamylase deficiency. Although as a group, these women had average IQ scores, they displayed a specific neuropsychological phenotype with significant strengths in verbal intelligence, verbal learning, verbal memory, and reading, and significant weaknesses in fine motor dexterity/speed and nonsignificant weaknesses in nonverbal intelligence, visual memory, attention/executive skills, and math. This suggests selective vulnerability of white matter and better preservation of gray matter. When the group was divided into symptomatic and asymptomatic subgroups, based on either clinical history or residual urea synthetic capacity, the asymptomatic subgroup outperformed the symptomatic subgroup on all tested domains of neuropsychological functioning. Furthermore, the amount of residual urea synthetic capacity was predictive of several end point cognitive measures. There was no correlation between neonatal versus late-onset mutation or between normal or abnormal allopurinol challenge and neuropsychological outcome. In sum, we identified a specific metabolic and neurocognitive phenotype in women heterozygous for ornithine transcarbamylase deficiency. The findings support the importance of maintaining meticulous metabolic control in children with urea cycle disorders, because even mildly symptomatic subjects demonstrate cognitive deficits.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Age of Onset
  • Amino Acid Metabolism, Inborn Errors / genetics
  • Amino Acid Metabolism, Inborn Errors / physiopathology*
  • Biomarkers
  • Cognition / physiology*
  • Female
  • Heterozygote*
  • Humans
  • Middle Aged
  • Mutation
  • Neuropsychological Tests
  • Ornithine Carbamoyltransferase / genetics
  • Ornithine Carbamoyltransferase Deficiency Disease*
  • Phenotype*
  • Polymorphism, Single-Stranded Conformational
  • Urea / metabolism


  • Biomarkers
  • Urea
  • Ornithine Carbamoyltransferase