Heritable urea cycle enzyme deficiency-liver disease in 16 patients

Document Type

Journal Article

Publication Date



The Journal of Pediatrics








The liver mitochondrial enzymes ornithine transcarbamylase and carbamyl phosphate synthetase I catalyze the first two steps in the Krebs-Henseleit pathway from ammonia to of either of these enzymes has been associated with severe and sometimes fatal hyperammonemia in infancy and childhood, but liver histology has usually been described as normal. The Reye syndrome also causes severe hyperammonemia and produces characteristic light microscopic changes in the liver. In addition, OTC and CPS activities have been shown to be depressed and it has been suggested that some cases of the Reye syndrome may reflect an inborn defect in OTC which predisposes the patient to the Reye syndrome. Review of the histopathology of 15 liver specimens from 13 patients with OTC deficiency and three liver specimens from three patients with CPS deficiency has disclosed the following: (1) hemizygous male infants with X-linked OTC deficiency had essentially normal liver histology, although fatally affected with extreme hyperammonemia; (2) in contrast, almost all heterozygous female children and adults had some histologic abnormalities, including nine with minor degrees of steatosis and eight with focal cell necrosis and inflammation, two of whom had piecemeal necrosis and stellate portal scarring; (3) livers from heterozygotes had discrete clusters of larger, pale-staining hepatocytes; (4) female heterozygotes had abnormal liver function, even after the hyperammonemia was controlled; (5) CPS deficient patients had essentially normal liver histology; and (6) neither OTC nor CPS deficiency was associated with a histologic picture which resembled that seen in the Reye syndrome. © 1979 The C. V. Mosby Company.

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