Citrin deficiency has three clinical phenotypes: (a) neonatal intrahepatic cholestasis due to citrin deficiency; (b) citrullinaemia type 2 (CTLN2), an adult form with recurrent hyperammonaemia and neuropsychiatric symptoms; (c) childhood form with failure to thrive and dyslipidaemia caused by citrin deficiency.
In adult patients with citrin deficiency, ureagenesis is impaired so that patients develop hyperammonaemia and hypercitrullinaemia with associated confusion, memory loss, restlessness and abnormal behaviour. The adult form of citrin deficiency has been reported almost exclusively in Japan.
Case We report a 57-year old woman, presented with a prolonged history of abnormal behavior, aggression, paranoia, and hyperactivity. There was evidence of non-convulsive status epilepticus on electroencephalogram, which subsequently improved with Levetiracetam, Phenytoin and Lamotrigine treatment. Liver function tests were deranged and serum ammonia was persistently raised up to 111 µmol/L with a fatty liver deposition on ultrasound. No responsible medication or primary liver or porto-shunt system was identified. Clinical features and serum ammonia improved with a high protein and low carbohydrate diet. Plasma amino acids showed no significant abnormalities except for an increased citrulline of 54 µmol/L. Genetic testing for SLC25A13 gene mutation was negative. Whole genome sequencing is being carried out. Treatment with sodium benzoate, dietary restriction of proteins and anti-epileptic medications resolved non-convuslive status epilepticus on EEG, and moderately improved hyperammonaemia.
Conclusion Correct diagnosis and specific dietary treatment is crucial to ensure a good prognosis in patients with hypercitrullinaemia. This should be considered as a differential diagnosis in patients with persistent non-hepatic hyperammonaemia. There might be as yet unrecognised gene defects responsible for hypercitrullinaemia.