Hyperammonaemic Encephalopathy Caused by Adult-Onset Ornithine Transcarbamylase Deficiency

Abstract

Hyperammonaemic encephalopathy in adults is a rare condition in the absence of liver disease and is associated with a high mortality and risk of permanent neurological deficits. Seldomly, the condition is caused by an inborn error of metabolism in the urea cycle, triggered by an exogenic factor such as gastrointestinal haemorrhage, gastric bypass surgery, starvation, seizures, vigorous exercise, burn injuries, or drugs hampering the elimination of ammonia. Here, we present a fatal case of an unrecognized genetic ornithine transcarbamylase deficiency (OTCD) presenting with a subacute progressive encephalopathy. We review the current literature and discuss the differential diagnosis and treatment options. As swift diagnosis and initiation of treatment is vital, awareness of hyperammonaemic encephalopathy and its possible causes can help improve the prognosis of this condition.

Keywords: adult onset; brain oedema; hyperammonaemia; ornithine transcarbamylase deficiency; subacute encephalopathy.

Figure 1

Schematic overview of the urea cycle. CPS1—carbamoyl phosphatase synthetase; OTC—ornithine transcarbamylase; ASS1—argininosuccinate synthase 1; ASL—argininosuccinate lyase; ARG1—arginase 1. Adapted from [4,18].

Figure 2

Schematic overview of the case. The patient had developed back pain 5 weeks prior to this hospital admission to investigate altered behaviour. Treatment was stopped due to cerebral herniation 10 days after admission. GCS—Glasgow Coma Score; MoCA—Montreal Cognitive Assesment score; CSF—cerebrospinal fluid; S—serum; CRP—C reactive peptide.

Figure 3

Family tree. Mutation analysis of the family showed the brother’s daughter (IV:5) to be an obligate carrier. The sister’s children (IV:6,7) were all found to be carriers. Oblique line through the box indicates deceased individual. Squares indicate males, and circles indicate females.