Acquired urea cycle amino acid deficiency and hyperammonaemic encephalopathy in a cat with inflammatory bowel disease and chronic kidney disease

Abstract

Case summaryA 5-year-old male neutered Persian cat was referred for investigation of a 4 week history of weight loss, inappetence and intermittent vomiting. Chronic kidney disease (CKD) and inflammatory bowel disease were diagnosed, and despite immunosuppressive therapy and assisted enteral nutrition, the cat experienced persistent anorexia, vomiting and severe weight loss. After 2 additional weeks of treatment, the cat developed acute-onset neurological signs associated with severe hyperammonaemia and was euthanased. Plasma amino acid assessment revealed deficiency of several amino acids involved in the urea cycle, including arginine.Relevance and novel informationTo our knowledge, this is the first reported case of an acquired urea cycle amino acid deficiency without nutritional deprivation in a cat. Several contributing factors were suspected, including intestinal malabsorption and CKD. This case demonstrates the importance of urea cycle amino acids in feline metabolism and possible necessity for parenteral supplementation, particularly in the context of persistent weight loss despite adequate enteral nutrition.

Hyperammonemia in azotemic cats

“…36 However, a recent case report did demonstrate acquired hypoargininemia in a cat with concurrent CKD and inflammatory bowel disease. 12 Hyperammonemia secondary to severe hypocobalaminemia has been reported in the dog 37 and cat. 9,10 Cobalamin deficiency results in increased methylmalonic acid (MMA), which indirectly inhibits carbamoyl phosphate synthetase 1, the rate-limiting enzyme of the urea cycle.…”

“…36 However, a recent case report did demonstrate acquired hypoargininemia in a cat with concurrent CKD and inflammatory bowel disease. 12…”

“…In cats, secondary hyperammonemia is most commonly due to hepatic disease (congenital or acquired portosystemic shunting), 8 but there are also reports of hyperammonemia secondary to cobalamin and arginine deficiency. 9–12 Urinary tract infections (UTIs) with urease-producing bacteria have been reported to cause hyperammonemia in dogs, although a similar finding has not been reported in cats. 13 In humans, non-hepatic hyperammonemia has also been reported with hematologic neoplasms, the use of certain drugs (eg, valproic acid, carbamazepine, asparaginase) and increased protein loading (total parenteral nutrition, gastrointestinal bleeding, status epilepticus).…”

Transient hyperammonaemia following epileptic seizures in cats

“…Importantly, in addition to seizures and liver disease, hyperammonaemia can also develop secondary to acquired and congenital amino acid deficiencies, urinary tract infections with urease-producing bacteria and cobalamin deficiency. 5,[22][23][24][25] It was beyond the scope of this project to test for the potential impact of possible metabolic defects as possible alternative agents of change with regard to hyperammonaemia. Such an investigation could be the subject of future research.…”

“…3,4 Hyperammonaemia can develop in patients with hepatic failure or shunting of portal blood, and it may also occur secondary to urea cycle enzyme deficiencies. 5 The ammonia load can also be excessive as a result of muscle activity. 6 The kidneys are another source of ammonia and its release changes with acute disturbances of the acid–base balance.…”