The first case of citrullinaemia type II in Europe: Clinical implications

A 40-year-old man of Pakistani origin presented with 3 months of episodic confusion. He was recently dismissed from work as a lead IT consultant because of his inability to concentrate. Brain imaging and routine blood biochemistry were normal and his symptoms were initially attributed to psychological issues. He was referred for a neurology opinion, and was found to have impaired psychometry and slow EEG suggestive of metabolic encephalopathy. His subsequent tests showed elevated plasma levels of ammonia, citrulline and arginine implicating citrullinemia type II. CSF lactate was also raised. Subsequent clinical deterioration was rapid, with development of cerebral oedema and death within the next 4 weeks. Genetic analysis revealed a novel mutation in SLC25A13. Mitochondrial mutation analysis was negative. Citrullinaemia type II (CTLN2) is a recessively inherited metabolic disorder caused by a deficiency in the hepatic mitochondrial-transporter citrin. It presents in infancy with jaundice, and as a hyperammonaemic encephalopathy in adulthood. We report the first case of CTLN2 in Europe, which is associated with a novel mutation in the SLC25A13 gene in a patient ethnically and geographically distinct from CTLN2 described previously in the literature. Further studies are ongoing to elucidate the molecular nature of this mutation which may represent a founder effect from newly-arrived families of South-Asian origin. CTLN2 should be considered as a possible cause of hepatic encephalopathy, as the early recognition of the disorder is essential for timely liver transplantation, the only known effective therapy to date for this condition.