We report the case of a 14-year-old girl admitted to PICU following a four-day history of vomiting, unusual behaviour and progressive drowsiness. She had depressed consciousness and encephalopathic features, thus requiring intubation and ventilation. The initial CT and MR scans were unremarkable and an encephalopathy screen, including plasma ammonia was performed on admission.
Shortly after admission the patient developed seizures and signs of raised intracranial pressure with a right fixed, dilated pupil. The pre-ictal ammonia concentration was markedly elevated at 638umol/L. A repeat urgent CT brain showed diffuse cerebral oedema with signs of brain herniation; neuroprotective measures were therefore initiated. Attempts to rapidly reduce ammonia levels by haemofiltration and infusions of sodium benzoate and phenylbutyrate were biochemically successful. Despite a quick decline in ammonia levels the patient developed central diabetes insipidus and showed no signs of neurological recovery, with persistent fixed, dilated pupils. Biochemical investigations strongly suggested a diagnosis of ornithine transcarbamylase deficiency (OTCD) with low citrulline and increased urinary orotic acid. DNA for mutation analysis and a liver biopsy or enzyme studies were sent to confirm the diagnosis. Brain stem testing 5 days post- admission confirmed brain stem death.
OTCD is the commonest inborn error of the urea cycle and shows X-linked inheritance. The classic presentation in male hemizygotes is with life threatening hyperammonaemic coma shortly after birth but milder variants present later. The phenotype in female heterozygotes is variable and depends on the pattern of X-chromosome inactivation in hepatocytes. This can range from severe neonatal encephalopathy to being completely asymptomatic throughout life. Survival and neurocognitive outcomes can be better than in severely affected males but are variable. Aggressive treatment of hyperammonaemic crises, dietary management with low protein diets, and alternative pathway therapy prevent further cognitive decline.
This case highlights the importance of early ammonia testing in encephalopathic patients regardless of age. A diagnosis of OTCD should be considered in patients with hyperammonaemia regardless of sex. Early recognition and appropriate treatment are critical to avoid severe brain damage and death.
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