Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21-year, multicentre study of acute hyperammonaemic episodes

Acta Paediatr. 2008 Oct;97(10):1420-5. doi: 10.1111/j.1651-2227.2008.00952.x. Epub 2008 Jul 17.


Aim: A large longitudinal interventional study of patients with a urea cycle disorder (UCD) in hyperammonaemic crisis was undertaken to amass a significant body of data on their presenting symptoms and survival.

Methods: Between 1982 and 2003, as part of the FDA approval process, data were collected on patients receiving an intravenous combination of nitrogen scavenging drugs (Ammonul sodium phenylacetate and sodium benzoate (10%, 10%)) for the treatment of hyperammonaemic crises caused by urea cycle disorders.

Results: A final diagnosis of a UCD was made for 260 patients, representing 975 episodes of hospitalization. Only 34% of these patients presented within the first 30 days of life and had a mortality rate of 32%. The most common presenting symptoms were neurological (80%), or gastrointestinal (33%). This cohort is the largest collection of patients reported for these diseases and the first large cohort in the United States.

Conclusion: Surprisingly, the majority (66%) of patients with heritable causes of hyperammonaemia present beyond the neonatal period (>30 days). Patients with late-onset presenting disorders exhibited prolonged survival compared to the neonatal-presenting group.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Age Factors
  • Amino Acid Metabolism, Inborn Errors / diagnosis*
  • Amino Acid Metabolism, Inborn Errors / epidemiology*
  • Amino Acid Metabolism, Inborn Errors / metabolism
  • Amino Acid Metabolism, Inborn Errors / mortality
  • Child
  • Child, Preschool
  • Female
  • France / epidemiology
  • Humans
  • Hyperammonemia / diagnosis*
  • Hyperammonemia / epidemiology*
  • Hyperammonemia / metabolism
  • Hyperammonemia / mortality
  • Incidence
  • Infant
  • Infant, Newborn
  • Longitudinal Studies
  • Male
  • Ornithine Carbamoyltransferase / metabolism
  • Ornithine Carbamoyltransferase Deficiency Disease / diagnosis*
  • Ornithine Carbamoyltransferase Deficiency Disease / epidemiology
  • Ornithine Carbamoyltransferase Deficiency Disease / metabolism
  • Ornithine Carbamoyltransferase Deficiency Disease / mortality
  • Prevalence
  • Quality of Life
  • Recurrence
  • Time Factors
  • United States / epidemiology
  • Urea / metabolism*


  • Urea
  • Ornithine Carbamoyltransferase