Yalelaan 8, 3584CL Utrecht, the Netherlands; e-mail: M.M.J.M. Zandvliet @vet.uu.nl.
Transient Hyperammonemia Due to Urea Cycle Enzyme Deficiency in Irish Wolfhounds
Article first published online: 5 FEB 2008
© 2007 American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 21, Issue 2, pages 215–218, March 2007
How to Cite
Zandvliet, M.M.J.M. and Rothuizen, J. (2007), Transient Hyperammonemia Due to Urea Cycle Enzyme Deficiency in Irish Wolfhounds. Journal of Veterinary Internal Medicine, 21: 215–218. doi: 10.1111/j.1939-1676.2007.tb02951.x
- Issue published online: 5 FEB 2008
- Article first published online: 5 FEB 2008
- Submitted May 30, 2006; Revised August 19, 2006; Accepted September 20, 2006.
- Amino acid;
- Congenital defect;
- Inborn error of metabolism
Background:Irish Wolfhounds frequently have a congenital portosystemic shunt, but a considerable proportion of the 6-to 8-wk-old pups has hyperammonemia in the absence of portosystemic shunting. This hyperammonemia causes no signs and is transient, normalizing at the age of 3–4 months.
Hypothesis:Transient hyperammonemia has a metabolic basis in Irish Wolfhounds.
Animals:Two related (same sire) litters of Irish Wolfhounds (17 pups) and their parents were studied.
Methods:Integrity of the portal circulation was examined by ultrasonography and scintigraphy. Absence of parenchymal liver disease was verified by liver biopsy. Amino acid profiles were measured in 4 pups and repeated in 2 of these pups when ammonia concentrations had normalized. The amino acid profiles were compared with those of healthy Irish Wolfhound pups.
Results:Fasting venous ammonia concentrations were high (113–622 μg/dL, 65–345 μmol/L) in all pups, whereas bile acids were within reference range in all but 1. The ammonia and bile acid concentrations from all parents were within reference range. Portosystemic shunting was excluded in all but 1 pup. Liver biopsy excluded significant lesions in all 10 pups examined. Hypercitrullinemia was found and persisted even when ammonia had normalized, at the expense of an increase in glutamine and asparagine.
Conclusions and Clinical Importance: Citrulline concentrations are controlled by the urea cycle enzymes argininosuccinase and argininosuccinate synthetase, and a defect in either of these enzymes may be responsible for the transient hyperammonemia in Irish Wolfhounds. Resolution of the hyperammonemia is associated with increased activity of alternative metabolic pathways forming glutamine and asparagine. Confirmation requires measurement of enzyme activities in liver tissue.