Ammonia and Coma - a Case Report of Late Onset Hemizygous Ornithine Carbamyltransferase Deficiency in 68-year-old Female

Background: Acute hyperammonemia without signs of common causes in the elderly might be challenging to identify. We report the oldest case known to date of a female patient with late onset ornithine carbamyltransferase deficiency (OTC), which was unmasked after a protein overload due to nutritional supplements. Our case illustrates how environmental factors (protein overload) in previously unknown OTC in the elderly leads to hyperammonemic encephalopathy and highlights that early treatment prevents persisting neurological deficits and should be considered in absence of common causes of hyperammonemic encephalopathy.

Case Presentation: A 68-year-old woman presented with acute confusion, which progressed into a deep coma (Glasgow-Coma-Scale score 3) within a few hours. The only remarkable finding was a plasma ammonia (NH3) concentration of 697 μmmol/l (range 12-47 μmmol/). Third party history revealed that the patient disliked meat for most of her life (meat = protein, which needs to be metabolized) and had taken nutritional supplements (since supplements often have a high protein-ratio) 2 days before the symptoms started. Protein catabolism results in NH3, which is metabolized via the urea cycle. Consequently, the acute hyperammonemia in our patient was thought to be related to an inherited metabolic disorder, which only unmasked itself as a result of an overload of the corresponding metabolite (in this case protein). Since ornithine carbamyltransferase deficiency (OTC) is the most common inherited urea cycle disorder, this diagnosis became likely and was confirmed later via genetic and metabolic testing (amino acids, orotic acid, etc.). After 2 weeks of treatment (dialysis, low-protein-diet, nitrogen-lowering medication) the patient was discharged in a healthy condition without any neurological deficits.

Conclusion: OTC is a x-chromosomal linked disorder, that usually manifests in newborn infants and children, but also rarely in adults and even rarer in the elderly (50- till 60-years-old), where it is probably underdiagnosed. In case of hyperammonemic encephalopathy - regardless of the underlying cause -, treatment should be started early to prevent persisting neurological deficits. OTC should be considered in absence of common causes of hyperammonemic encephalopathy.