Neurologic outcome in children with inborn errors of urea synthesis. Outcome of urea-cycle enzymopathies

N Engl J Med. 1984 Jun 7;310(23):1500-5. doi: 10.1056/NEJM198406073102304.


We studied 26 children with inborn errors of urea synthesis who survived neonatal hyperammonemic coma. There was a 92 per cent one-year survival rate associated with nitrogen-restriction therapy and stimulation of alternative pathways of waste nitrogen excretion. Seventy-nine per cent of the children had one or more developmental disabilities at 12 to 74 months of age; the mean IQ was 43 +/- 6. There was a significant negative linear correlation between duration of Stage III or IV neonatal hyperammonemic coma and IQ at 12 months (r = -0.72, P less than 0.001) but not between the peak ammonium level (351 to 1800 microM) and IQ. There was also a significant correlation between CT abnormalities and duration of hyperammonemic coma (r = 0.85, P less than 0.01) and between CT abnormalities and concurrent IQ (r = -0.75, P less than 0.02). These results suggest that prolonged neonatal hyperammonemic coma is associated with brain damage and impairment of intellectual function. This outcome may be prevented by early diagnosis and therapy.

Publication types

  • 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 / diagnostic imaging
  • Amino Acid Metabolism, Inborn Errors / therapy
  • Ammonia / blood
  • Argininosuccinate Synthase / deficiency
  • Argininosuccinic Aciduria
  • Brain / diagnostic imaging
  • Brain Damage, Chronic / etiology
  • Carbamoyl-Phosphate Synthase (Ammonia) / deficiency
  • Child
  • Child, Preschool
  • Coma / etiology
  • Female
  • Humans
  • Infant
  • Intellectual Disability / etiology
  • Intelligence Tests
  • Male
  • Nervous System Diseases / etiology*
  • Ornithine Carbamoyltransferase Deficiency Disease
  • Seizures / etiology
  • Tomography, X-Ray Computed
  • Urea / biosynthesis*


  • Ammonia
  • Urea
  • Carbamoyl-Phosphate Synthase (Ammonia)
  • Argininosuccinate Synthase