INTRODUCTION: Ammonia is a well-known toxin, mostly studied in Hepatic encephalopathy. While, it is related to severe liver disease in 90% cases, the remaining 10% is constituted by disturbances in its excretion or related to over production from other etiologies. [1] Awareness of hyperammonemia in absence of severe hepatic disease may lead to lifesaving prompt diagnosis and treatment. We present a mysterious case of recurrent severe hyperammonemia without known liver disease. CASE DESCRIPTION/METHODS: A 53 year old male with prior history of well controlled hypertension presented to the emergency department with unresponsiveness. On exam, he was unconscious with occasional spontaneous eye opening and a left gaze preference. CT head and CT angiogram of neck did not reveal any acute abnormalities. Liver enzymes and Bilirubin were normal. Blood alcohol level was 0.089gm/dl%. EEG showed diffuse encephalopathy. Serum ammonia was 705 umol/L. He was started on lactulose. His mentation improved in a day and repeat serum ammonia was 25umol/L. Ultrasound liver and CT abdomen ruled out cirrhosis and gall bladder disease. He was discharged home with a prescription of lactulose. He returned to the ED with another episode of unresponsiveness a month later and was found to have elevated serum ammonia of 213 umol/L. Levetiracetam was started empirically with suspicion of recurrent seizures causing this unresponsiveness. He continued to have similar episodes of hyperammonemic encephalopathy. Orotic acid in urine was high (>200 mmol/mol creatinine ), clinching the diagnosis of ornithine transcarbamylase (OTC) deficiency. He was advised to consume a low protein diet and was prescribed L-carnitine along with lactulose. DISCUSSION: Ammonia directly affects neuronal electric activity by inhibiting the generation of both excitatory and inhibitory postsynaptic potentials. Secondary hyperammonemia occurs commonly in the presence of hepatic disorders leading to portosystemic encephalopathy. Less common causes include drugs like valproate, post-chemotherapy, gastric bypass surgery. Causes of primary hyperammonemia in adults include milder forms of urea cycle enzyme deficiencies like OTC, argininosuccinate lyase. Noncirrhotic hyperammonemia as a cause of altered mental status remains a diagnosis of exclusion and requires high index suspicion. Treatment options include lactulose, l-carnitine, and drugs to lower cerebral edema if patient has MRI findings. Liver transplantation is an important treatment modality in urea-cycle disorders.