Case Presentation: This is a case of a 38-year-old female with a relevant past medical history of rheumatoid arthritis who presented with nausea, vomiting, and altered mental status. She was found to have partially compensated anion gap metabolic acidosis and tonic-clonic seizures requiring intubation. Pertinent diagnostic workup revealed a significantly elevated ammonia level of 245 mcmol/L, with no evidence of hepatic synthetic dysfunction. Imaging at that time showed CT head significant for cerebral edema and brain MRI concerning for intracranial hypertension. Infectious workup showed no evidence of urease-producing organisms, a volatile alcohol screen did not reveal any likely causes for the patient’s symptoms, and a urine drug screen was negative. During the hospitalization, nutritional workup was notable for low vitamin B6 level at 5.6 mcg/L (reference range 5-50 mcg/L), extremely low total serum carnitine at 5 mcmol/L (reference range 35–80 mcmol/L), very low free serum carnitine at 2 mcmol/L (reference range 20–65 mcmol/L), low vitamin A at 23.9 mcg/dL (reference range 32.5-78 mcg/dL), and low vitamin D 25-OH at 18 ng/mL (reference range 30-80 ng/mL). After extubation, the patient’s mental status gradually improved and ammonia levels normalized; however, she continued to experience postprandial vomiting. An EGD was performed, revealing duodenal mucosa with mild to moderate intraepithelial lymphocytosis and mild villous blunting compatible with celiac disease. The patient was discharged on a strict gluten-free diet and levocarnitine supplementation with recommendations for outpatient follow-up. Ultimately, the patient’s acute encephalopathy from hyperammonemia is presumed to be due to carnitine deficiency secondary to malabsorption from undiagnosed celiac disease. Carnitine is crucial for the proper functioning of the urea cycle and ammonia detoxification. It facilitates the transport of fatty acids into the mitochondria for oxidation, which is essential for energy production required for the urea cycle to operate effectively.
Discussion: Hyperammonemia is characterized by ammonia ≥ 50 mcmol/L in the blood. The condition can arise from a variety of causes, including inherited genetic metabolic disorders or acquired etiologies such as liver disease, infections, medication effects, or malabsorption syndromes. Altered mental status is a common yet nonspecific presenting symptom that requires a broad and thoughtful diagnostic approach. This case illustrated how clinical reasoning evolves when initial workup, including basic labs, imaging, infectious studies, and toxin screening, does not reveal a clear cause. As more common etiologies were ruled out, it became necessary to consider more nuanced possibilities such as medication side effects, metabolic disorders, or nutritional deficiencies.
Conclusions: This case underscores the need to consider nutritional and metabolic contributors when evaluating hyperammonemia without clear hepatic involvement. While this case offered insight into the role of carnitine in the urea cycle, it reinforced the value of a systematic and evolving diagnostic approach.