P3970 - Hyperammonemia Not Just From Cirrhosis: A Case of Late Onset Urea Cycle Disorder

Alex Liu, MD¹, David Chiang, MD, PhD¹, Mengfei Liu, MD^2
1Mayo Clinic, Rochester, MN; ²Yale School of Medicine, New Haven, CT

Introduction: Urea cycle disorders are rare, and patients can present in adulthood. A high level of suspicion is needed to diagnosis this in cases of encephalopathy that are not completely due to hepatic dysfunction.

Case Description/Methods: The patient is a 38-year-old female with known alcoholic hepatitis, concern for cirrhosis, and obesity who was admitted for altered mental status. She has a significant drinking history and 4 weeks prior to admission was admitted for alcoholic hepatitis with an elevated Maddrey’s discriminant function. At the time, a CT scan demonstrated hepatomegaly and hepatosteatosis. She was discharged with lactulose and prednisone with regular outpatient follow-up. However, the patient developed nausea, vomiting, and altered mental status requiring admission. She was initially treated with lactulose and rifaximin for presumed hepatic encephalopathy, with clinical deterioration requiring intubation. Infectious, neurologic, and hepatic work-up was unrevealing. An ammonia level was obtained in the ICU at 247 mcmol/L, elevated from 87 mcmol/L on admission. Given the negative exhaustive work-up (including EEG, LP, and MRI), an urea cycle disorder was suspected. Indeed, urine orotic acid was elevated at 1.8 (0.4 – 1.4 mmol/mol creatinine ). Genetic testing was positive for carbamoyl phosphate synthetase 1 deficiency heterozygosity. Liver biopsy was positive for grade 3-4 fibrosis. The patient was initiated on Molecular Adsorbent Recirculating System therapy and mannitol. Genetics recommended starting enteral ammonium binders as well as a modified protein diet. Slowly, over the course of 5 months, the patient improved and was ultimately returned home.

Discussion: We present a case of severe hyperammonemia in the setting of CPS1 heterozygosity, advanced liver fibrosis, and active alcohol use. Typically, CPS1 deficiency presents in the neonatal period with elevated serum ammonia and orotic acid, but adult onset has been noted before, and heterozygous presentations typically do not manifest signs or symptoms. The current hypotheses include underlying chronic liver disease with increase metabolic demand from stress (hepatitis), alcohol, and steroid use. Alternatively, it is possible another mutation resulted in underlying chronic liver disease. This case highlights how hyperammonemia is not always sorely from hepatic encephalopathy and to consider genetics and metabolic disorders in the workup, especially if the patient does not improve.


Disclosures:


Alex Liu, MD¹, David Chiang, MD, PhD¹, Mengfei Liu, MD². P3970 - Hyperammonemia Not Just From Cirrhosis: A Case of Late Onset Urea Cycle Disorder, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.