CASE PRESENTATION: A 46- year old female with history of fibromyalgia presented with memory changes and abdominal discomfort for two weeks. In Emergency Department rapid decline in mental status and acute hypoxic respiratory failure was noted requiring endotracheal intubation and admission to intensive care unit. Initial investigations showed leukocytosis with neutrophilia, mild transaminitis and minimally elevated ammonia level, 77 uMol/l (nl 18- 72). Serum and urine drug screens were positive for tricyclic antidepressants with prolong cQT interval. Chest imaging revealed dependent pulmonary infiltrates.Computed tomography (CT) of head was unremarkable. CT abdomen showed hepatic steatosis with no features of cirrhosis. She was treated with bicarbonate infusion, lactulose and rifaximin. Subsequently on day three, ammonia levels rose to 317 and repeat CT head showed diffuse cerebral edema. In view of medically refractory hyperammonemia, continuous venovenous hemodialysis (CVVHD) was initiated with subsequent reduction in ammonia levels. Liver biopsy revealed with stage II fibrosis with negative copper and iron stains, insufficient to result in portosystemic shunting. Finally urine studies showed elevated orotic acid levels and glutamine levels with low citrulline amino acid consistent with ornithine transcarbamylase (OTC) deficiency, an enzyme in urea cycle. Patient subsequently underwent percutaneous tracheostomy and gastrostomy in view of poor neurologic recovery.