A Case of Hyperammonemia Not Attributable to Liver Disease and Treated With IV Ammonia Scavengers

Abstract

Hyperammonemia is a serious metabolic condition marked by elevated ammonia levels in the blood, leading to neurological damage and systemic complications if untreated. While often associated with liver dysfunction, inborn metabolic errors such as fatty acid oxidation defects, pyruvate metabolism disorders, urea cycle disorders (UCDs), urea splitting bacterial infections, hemato-oncological disorders, and portosystemic shunts are less commonly recognized but significant causes, particularly outside neonatal populations. These metabolic errors, due to partial enzyme deficiencies, may present later in life with atypical symptoms. We report an acute presentation of a female patient in her late fifties with a background of noncirrhotic hyperammonemia of unknown etiology, controlled with oral sodium benzoate. She presented with ataxia, altered mental status, and delusion. The laboratory evaluation revealed significantly elevated ammonia levels, which did not respond to an increased dose of oral sodium benzoate, and she required intravenous ammonia scavengers to achieve acceptable levels. We further discuss several investigations done to establish a cause for her hyperammonemia and a psychiatric diagnosis of erotomania/de Clerambault's syndrome secondary to recurrent hyperammonemia. Although her biochemical workup had some features suggestive of type 2 citrulline deficiency, SLC25A13 mutation analysis for citrin deficiency and an extended R98 panel were negative. Thus, highlighting the complexity of diagnosis of inborn metabolic errors and treatment of metabolic hyperammonemia in the absence of an established diagnosis. It also emphasizes the need for heightened awareness and prompt treatment of inborn metabolic errors in adult patients, following the British Inherited Metabolic Disease Group (BIMDG) management guidelines to prevent severe neurological outcomes. Multidisciplinary management, including liaison with specialists in metabolics, gastroenterology, and dietetics, is crucial for optimizing patient care and outcomes in such complex cases.

Keywords: ammonia scavengers; arginine; non-cirrhotic hyperammonemia; ornithine transcarbamylase deficiency; orotic acid; phenylbutyrate; plasma amino acids; sodium benzoate; type ii citrullinemia; urea cycle disorder.