Case Presentation:

Mrs. AS is a 76–year–old female with PMH of CHF, PVOD, T2DM, atrial fibrillation, osteomyelitis, and CKD who was admitted with recurrence of intermittent mental status changes. She was functioning at her normal level, interactive, and taking care of her ADLs until August 2011 when she had the subacute onset of altered mental status. She was found to have an elevated ammonia level and hypothyroidism, the latter attributed to initiation of amiodarone for her atrial fibrillation. She had multiple admissions with a similar presentation to an OSH during which time medications would be adjusted including increases in Synthroid dose and placement on an aggressive lactulose regimen. She would improve substantially. LFTs were always normal, and the etiology of hyperammonemia was never determined. Upon admission, labs were again notable for an elevated ammonia of 133, negative UA and CXR, absence of leukocytosis, normal LFTs, and markedly elevated TSH of 36.30 with normal FT4 of 1.66. Head CT and MR brain were without acute pathology. Endocrinology felt the patient did not have any evidence of myxedema coma (bradycardia, hypothermia) and that her hypothyroidism was not the major cause of her altered mental status. Hepatology noted that in the absence of known liver disease, normal transaminases, and ultrasound demonstrating liver of normal texture, her hyperammonemia was non–specific and not related to liver disease. She was continued on her home medications and aggressive lactulose therapy, with resultant clearing of her mental status back to baseline. She underwent hyperammonemia work–up for a urea cycle disorder with quantitative plasma amino acid analysis and urine orotic acid results. Following discharge, results returned, with >2–fold increase in serum citrulline, mild increase in arginine, and absence of argininosuccinic acid. No peak of orotic acid by GCMS.


Mrs AS’s plasma amino acid profile was felt to be consistent with disorder of urea cycle metabolism, most likely deficiency of arginosuccinic synthetase (ASS), a.k.a. adult–onset type II citrullinemia. This disorder often presents in adulthood (though patient’s age of presentation far beyond norm for even adult–onset type). It primarily affects the CNS, with confusion, restlessness, memory loss, and behavioral changes. While patients can be cured of disease with liver transplantation, referral was deferred in this case given the patient’s advanced age and comorbidities. She was referred to nutrition as dietary modification is a mainstay of therapy. In contrast to low–protein diets recommended in most urea cycle disorders, patients with adult–onset type II citrullinemia often fare better with carbohydrate–restricted diets.


Consider urea cycle disorders in patients who present with mental status changes, hyperammonemia, and normal hepatic function. Work–up includes plasma amino acids and urine orotic acid. Management includes nutrition counseling. In eligible patients, liver transplantation can be curative.