Abstract Introduction The urea cycle converts toxic ammonia into urea for excretion. Body nitrogen originates from muscle and dietary proteins. Pathway defects causing hyperammonemia, classically occur due to congenital enzyme deficiencies that first present in childhood. Rarely, adults can develop acquired urea cycle dysfunction in the setting of severe nutritional deficiencies. Ornithine transcarbamylase (OTC) is a key urea cycle enzyme that catalyzes the conversion of ornithine and carbamoyl phosphate into citrulline. We present a case of acquired OTC dysfunction secondary to profound zinc deficiency. Case A 54-year-old woman with a history of cyclic vomiting syndrome and gastric bypass surgery presented with altered mental status and recurrent falls. On arrival, she was alert and oriented. Initial labs revealed mildly elevated arterial ammonia (89 µmol/L), hypokalemia, and hypophosphatemia. Initial CT head without contrast did not reveal acute abnormalities. Lumbar puncture had unremarkable studies. Despite supportive management, her mental status declined and she required intubation on hospital day four. She then developed status epilepticus, with repeat ammonia rising to 384 µmol/L and CT demonstrating acute cerebral edema (see image 1). Continuous renal replacement therapy (CRRT) was started for ammonia clearance. Liver biopsy demonstrated bridging fibrosis and nodule formation consistent with new diagnosis of cirrhosis. However, cerebral edema and hyperammonemia secondary to cirrhosis does not occur acutely except in Wilson’s disease. Therefore, new cirrhosis could not solely explain her neurologic deficits. Metabolic testing revealed severe zinc deficiency (25.1 µg/dL) and low copper (45.2 µg/dL), while genetic testing for inherited urea cycle disorders was negative. Her hyperammonemia was attributed to acquired OTC dysfunction secondary to severe zinc deficiency. With CRRT, zinc and copper supplementation, and a low-protein diet, ammonia levels gradually improved. Her course was complicated by critical illness myopathy and prolonged ventilator dependence, requiring tracheostomy and gastrostomy before discharge to a long-term care facility. Discussion Bariatric surgery effectively reduces obesity-related morbidity but increases the risk of micronutrient deficiencies. Risk is amplified in patients with additional risk factors for malnutrition, such as cyclic vomiting. Severe zinc deficiency can impair OTC activity, rarely leading to non-hepatic hyperammonemia with potentially fatal outcomes. This uncommon presentation highlights the use of serial arterial ammonia outside of acute liver failure. In encephalopathic adults with risk factors for malnutrition, early evaluation for micronutrient deficiencies is essential, as timely repletion and clearance may prevent irreversible neurologic injury and improve survival. Image 1: CT Head Without Contrast Demonstrating Loss of Grey-White Matter Differentiation This abstract is funded by: None
Sakher et al. (Fri,) studied this question.