Abstract
Extract: Six related subjects with severe feeding problems in infancy, hyperammonemia, hyperornithinenia, and homocitrullinuria are reported. The clinical picture includes episodic motor and mental impairment, seizures, intellectual deficits that vary from severe to very mild and, in two cases, a bleeding tendency early in life. The pedigree indicates autosomal recessive inheritance.
In a liver biopsy in one patient decreased activity of carbamyl phosphate synthetase I (CPS I, EC. 2.7.2.5) was found. Enzymatic assays on peripheral leukocytes in all six subjects confirmed the liver results. Loading studies with ornithine and citrulline were consistent with a defect early in the urea cycle. Homocitrullinuria appeared to arise from excessive synthesis from lysine, but there was no impairment of the main lysine catabolic pathway.
Large and bizarrely shaped hepatic mitochondria with curious periodic (350–400Å) membranes were observed ultrastructurally.
Speculation: Clinical entities in which liver CPS I deficiency has been reported represent a heterogeneous group. This heterogeneity may arise because the assays currently in use do not differentiate between individual steps in the complex synthetic reaction catalyzed by this enzyme. Associated abnormalities in ornithine transport into the hepatic mitochondria in some may also contribute to the varying expression of this group of disorders. It is conceivable that some unusual periodic structures observed just inside the inner mitochondrial membranes are related to altered ornithine mitochondrial entry.
This disorder adds to the evidence from other inborn errors that there are one or more ways in which lysine metabolism and the urea cycle are specifically interrelated, but the details remain obscure.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gatfield, P., Taller, E., Wolfe, D. et al. Hyperornithinemia, Hyperammonemia, and Homocitrullinuria Associated with Decreased Carbamyl Phosphate Synthetase I Activity. Pediatr Res 9, 488–497 (1975). https://doi.org/10.1203/00006450-197505000-00006
Issue Date:
DOI: https://doi.org/10.1203/00006450-197505000-00006
Keywords
This article is cited by
-
Liver involvement in urea cycle disorders: a review of the literature
Journal of Inherited Metabolic Disease (2017)
-
The hyperornithinemia–hyperammonemia-homocitrullinuria syndrome
Orphanet Journal of Rare Diseases (2015)
-
Hyperornithinaemia- hyperammonaemia- homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter
Nature Genetics (1999)
-
Abnormality of citrulline synthesis in liver mitochondria from patients with hyperornithinaemia, hyperammonaemia and homocitrullinuria
Journal of Inherited Metabolic Disease (1987)
-
A new family affected by the syndrome of hyperornithinaemia, hyperammonaemia and homocitrullinuria
Journal of Inherited Metabolic Disease (1987)