Hyperammonemia in absence of hepatic dysfunction: a diagnostic challenge and therapeutic dilemma

SESSION TITLE: Critical Care Case Report Posters 63 SESSION TYPE: Case Report Posters PRESENTED ON: 10/09/2023 12:00 pm - 12:45 pm INTRODUCTION: Ammonia, a known neurotoxin, can cross the blood-brain barrier precipitating encephalopathy and seizure by increasing neurotransmitter release and by promoting cerebral edema. Arterial ammonia levels even correlate with the degree of encephalopathy in acute liver failure. Hyperammonemia (HA) - a common manifestation of hepatic synthetic dysfunction, could also be seen in absence of liver disease. Urea cycle disorders (UCDs), infection with urease-producing organisms, malignancy, seizure, and drug toxicity can cause non-cirrhotic HA. We present a puzzling case of hyperammonemia in a patient without known liver disease. CASE PRESENTATION: A 50-years-old female with hypertension presented with progressive worsening of mental status. On arrival, her GCS score was 7 and she was subsequently intubated for airway protection. CT head was unremarkable. Labs significant for leukocytosis, elevated procalcitonin, and urinalysis was consistent with urinary tract infection. Blood and urine cultures were sent; broad spectrum antibiotics were initiated. Serum ammonia, done for work-up of encephalopathy, came back at 171 µmol/L. Abdominal ultrasound with Doppler did not show liver nodularity or any evidence of portal hypertension. Markers of hepatic synthetic function including bilirubin, albumin, coagulation panel were within normal range. She was started on lactulose and rifaximin. Subsequent hospital course was complicated by a new-onset generalized seizure and a progressively deepening coma despite weaning sedation. EEG showed diffuse slowing. Repeat ammonia level was 326 µmol/L. Her blood glucose, electrolytes, and acid-base status remained within normal range. Urine culture grew Pseudomonas aeruginosa. Patient was started on continuous renal replacement therapy (CRRT) for ammonia clearance with resultant precipitous drop in serum ammonia. Unfortunately, in accordance to her wish, family at this point transitioned her towards comfort cares. DISCUSSION: UCDs are the most common cause of non-cirrhotic HA and usually presents in childhood. However, patients with partial deficiency of urea-cycle enzymes could stay asymptomatic till late in adulthood when a triggering event (e.g. infection, gastric bypass surgery etc.) could unmask the condition. Clinical presentation may vary from mild irritability, lethargy, disorientation to profound obtundation and even seizure. In our patient, without clear evidence of liver disease and with normal blood glucose and anion gap, the diagnosis of UCDs is strongly suggested. Additional biochemical testing is necessary to establish the diagnosis and to identify the specific enzyme deficiency. Lactulose, sorbitol, rifaximin remain first line medical therapy. Sodium phenylacetate-sodium benzoate, an ammonia scavenger, is now approved in United States for proximal UCDs. Extracorporeal therapies including hemodialysis, peritoneal dialysis, and CRRT have been tried with varying degree of success in refractory HA. CONCLUSIONS: Even in absence of established liver disease, it is prudent to consider non-cirrhotic HA as a differential for encephalopathy and seizure. REFERENCE #1: Upadhyay R, Bleck TP, Busl KM. Hyperammonemia: What Urea-lly Need to Know: Case Report of Severe Noncirrhotic Hyperammonemic Encephalopathy and Review of the Literature. Case Rep Med. 2016;2016:8512721. doi: 10.1155/2016/8512721. REFERENCE #2: Hahn, Katherine J. MD1; Sarges, Philip MD1; Bull-Henry, Kathy P. MD2. Fatal Hyperammonemia: A Case of Urea Cycle Disorder Unmasked After Roux-en-Y Gastric Bypass: 917. American Journal of Gastroenterology 110():p S395, October 2015. REFERENCE #3: Wijdicks EFM. Hepatic encephalopathy. N Engl J Med 2016; 375:1660-1670. DOI: 0.1056/NEJMra1600561. DISCLOSURES: No relevant relationships by Peter Fahim No relevant relationships by Meenakshi Ghosh No relevant relationships by Nikhil Jagan No relevant relationships by Tharun Kotaru No relevant relationships by Abhisekh Sinha Ray