Case of Nutritionally Driven Acquired Urea Cycle Disorder

A recent article describes a case of nutritionally driven acquired urea cycle disorder with carnitine deficiency leading to severe hyperammonemia, encephalopathy, and extensive MRI changes. All resolved completely with the correction of the underlying essential amino acid deficiency.

"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.

Understanding Hyperammonemia

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
• Valproic acid toxicity

Ammonia is neurotoxic and can lead to cerebral edema.

Urea Cycle Disorders

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.

Case Report

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. MRI brain indicated 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.

Study 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.

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