Liver transplantation in a case of argininaemia

De¢ciency of arginase (EC 3.5.3.1), which converts arginine to urea and ornithine, is a rare autosomal recessive disease (McKusick 207800) caused by mutations in the ARG1 gene on chromosome 6q23.Onset is usually in childhood and clinical manifestations include progressive spastic paraparesis and mental slowing.In contrast to other urea cycle disorders (UCDs), liver involvement is less frequent and usually not as severe as, for instance, that observed in ornithine carbamyltransferase de¢ciency or in citrullinaemia.Moreover, while patients with other UCDs are at risk for intercurrent hyperammonaemic episodes even when they are on aggressive nutritional and dietary management, recurrent hyperammonaemia is not a primary feature of argininaemia (Colombo 1992).Consistently, patients with argininaemia are scarcely considered as candidate for liver transplantation.However, the rationale for orthotopic liver transplantation (OLT) still stands in this condition, because it would replace a de¢cient enzyme with an active hepatic arginase.We report a successful OLT in a patient with arginase de¢ciency in whom severe liver involvement was the only clinical manifestation.The proposita had an uneventful perinatal and neonatal period.At birth, she weighed 3050 g (P25), her height was 50 cm (P50) and her head circumference was 33.5 cm (P10).At age 2 months, cholestatic jaundice and hepatosplenomegaly were detected.Laboratory investigations showed total serum bilirubin of 186 mmol/L (normal < 17), conjugated serum bilirubin 161 mmol/L (normal < 3:5), SGOT 186 UI/L (normal < 56), SGPT 530 UI/L (normal < 39), gGT 85 UI/L (normal < 45), total cholesterol 7.1 mmol/L (normal 3.4^4.8),thromboplastin time 55.3 s (normal 35 s), prothrombin time 33.9 s (normal 14 s).Plasma arginine concentrations were elevated (1756 mmol/L).A liver biopsy revealed porta-porta septa, canalicular cholestasis, ductular proliferation and mononuclear portal in¢ltrates.The di¡erential diagnosis included extrahepatic biliary atresia, choledocal cyst, a 1 -antitrypsin de¢ciency and infectious diseases (TORCH, syphilis, B hepatitis), all ruled out by appropriate testing.De¢ciency of arginase A 1 activity was con¢rmed in blood red cells.Molecular genetic analyses detected the homozygous R21X mutation in the ARG1 gene.She was put on a low-protein,