Pediatric Liver Transplantation as Definitive Therapy for Urea Cycle Disorders

Abstract

Background: Liver transplantation (LT) has emerged as a surgical cure for urea cycle disorders (UCDs). LT eradicates the risk of hyperammonemia, removes dietary restrictions, and the need for nitrogen scavenging medications. Methods: To determine the long-term outcomes of LT for UCDs, charts of children with UCD who underwent LT were retrospectively reviewed at an academic institution between 2000-2011. Results: 19 patients with UCD underwent LT at a mean age of 4.6 years. Six (32%) patients had OTC-deficiency, five (26%) patients had carbamylphosphate synthetase (CPS) deficiency, four (21%) patients had argininosuccinic acid lyase deficiency, and four (21%) patients had citrullinemia. Fourteen (74%) patients were diagnosed during the neonatal period, while four (21%) patients were diagnosed after a positive newborn screen. Eleven (58%) patients received a whole liver graft, seven patients (37%) a reduced-size graft, and one patient received a living-donor graft. Mean 5-year patient survival was 100 %, and allograft survival was 95%. Postoperative complications included hepatic artery thrombosis (n=1), chylothorax (n=1), and bowel perforation (n=1). Mean peak blood ammonia (NH3) at presentation was 805 μmol/L (median 477, range 178-2969, normal < 30-50). After transplantation, there were no episodes of hyperammonemia. Eight patients were diagnosed with some degree of developmental delay before transplantation, which remained stable after transplantation. The patients without psychomotor developmental delay before transplantation maintained their cognitive abilities. One patient with CPS deficiency and two patients with OTC deficiency have continued citrulline supplementation post-transplant because of persistently low citrulline levels. Conclusions: In patients with UCDs, LT is associated with the eradication of hyperammonemia, removal of dietary restrictions, and potentially improved psychomotor development compared to historical controls. Long-term follow-up is underway to evaluate whether LT at an early age (< 1 year) will attain improved cognitive development over lifetime.[Table: Characteristics of Transplant Patients]