Acquired hyperammonemia and carnitine deficiency mimicking urea cycle disorder: Case study

"It is important to find the etiology of underlying metabolic derangements and should accordingly treat and prognosticate," the researchers wrote. The findings were presented at the American Academy of Neurology (AAN) annual meeting in 2024.

Hyperammonemia is caused mostly by defects or overproduction in detoxification due to liver disorders. Rare causes of hyperammonemia include fatty acid oxidation disorder, urea cycle disorder, Reye syndrome, organic acidemias, and valproic acid toxicity. Ammonia is neurotoxic and can lead to cerebral edema.

Urea cycle disorders are a group of rare genetic conditions characterized by deficiencies in enzymes responsible for detoxifying ammonia in the body. These disorders often present with symptoms such as lethargy, vomiting, seizures, and hyperammonemia, posing significant challenges in diagnosis and management.

Michelle DeJesus Brazitis and Beenish Javaid from the USA report a case of a middle-aged woman with chronic alcohol-related necrotizing pancreatitis presenting with myoclonic status epilepticus with MRI brain indicating extensive symmetric T2 hyperintensity and diffusion restriction throughout the bilateral cerebral cortex with relative sparing of white matter, brainstem, deep gray nuclei, and cerebellum.

Workup revealed resistant (defiant to medical therapy and CRRT) and severe (265 u mol/L) hyperammonemia despite lack of cirrhosis, portal venous congestion, or inciting medications.

The study led to the following findings:

· Metabolic-genetic workup revealed a metabolic pattern-- elevated urine orotic acid and glutamine with low total and free citrulline level-- consistent with proximal urea cycle defect likely OTC- Ornithine transcarboxylase deficiency or CPS1- Carbamoyl phosphate synthetase 1 deficiency.

· The next-generation sequencing test was negative for any genetic cause (Urea cycle enzymes or transporters) of hyperammonemia. Thus, chronic pancreatitis leading to exocrine pancreatic insufficiency, protein, and micronutrient malnutrition was considered to be the etiology of acquired/secondary urea cycle dysfunction leading to hyperammonemia.

· IV Scavenger therapy with Arginine, L Carnitine, and ammonul- a combination of sodium benzoate and sodium phenylacetate contributed to the resolution of hyperammonemia, encephalopathy, and MRI changes.

In conclusion, recognizing acquired hyperammonemia secondary to L-carnitine deficiency as a potential mimic of urea cycle disorders is paramount for optimizing patient care and preventing unnecessary interventions.

"Further research is warranted to elucidate the underlying mechanisms and identify effective therapeutic strategies for this rare metabolic condition," the researchers wrote.

"It is important to find the etiology of underlying metabolic derangements and should accordingly treat and prognosticate," they concluded. 

Reference:

10.1212/WNL.0000000000204946