Objective:

NA

Background:

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

Design/Methods:

We report a case of 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, deep gray nuclei, brainstem, and cerebellum. Work up revealed severe (265 u mol/L) and resistant (defiant to medical therapy and CRRT) hyperammonemia despite lack of cirrhosis, portal venous congestion or inciting medications.

Results:

Metabolic-genetic work up revealed a metabolic pattern-- elevated glutamine and urine orotic acid 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 secondary/acquired urea cycle dysfunction leading to hyperammonemia. IV Scavenger therapy with L Carnitine, Arginine and ammonul- combination of sodium benzoate and sodium phenylacetate contributed to resolution of hyperammonemia, encephalopathy and MRI changes.

Conclusions:

We present 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 correction of underlying essential amino acid deficiency. It is important to find the etiology of underlying metabolic derangements and should treat and prognosticate accordingly.