title: Transient hyperammonemia due to urea cycle enzyme deficiency in Irish wolfhounds.
abstract: 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.
  
  
  OBJECTIVE
  Transient hyperammonemia has a metabolic basis in Irish Wolfhounds.
  
  
  METHODS
  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 microg/dL, 65-345 micromol/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
  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.
authors.affiliation: Department of Clinical Sciences of Companion Animal Medicine, Faculty of Veterinary Medicine, Utrecht University, The Netherlands. M.M.J.M.Zandvliet@vet.uu.nl
authors.forename: M M J M
authors.initials: MM
authors.lastname: Zandvliet
authors.forename: J
authors.initials: J
authors.lastname: Rothuizen
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000151:congenital / Q000175:diagnosis*; D004285:Dogs; D005260:Female; D022124:Hyperammonemia / Q000151:congenital / Q000175:diagnosis / Q000662:veterinary*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000662:veterinary*; D014508:Urea / Q000378:metabolism*
chemical_list: D014508:Urea