Liver transplantation for neonatal‐onset citrullinemia

Abstract

Citrullinemia or ASS deficiency in its classical form presents in the neonatal period with poor feeding, hyperammonemia, encephalopathy, seizures, and if untreated can be fatal. Despite advances in medical therapy, neurocognitive outcomes remain suboptimal. LT has emerged as a potential management option. A retrospective single-center review identified 7 children with a median age of 1.1 years (range, 0.6-5.8) at referral. Five children presented clinically, and 2 were treated prospectively from birth due to positive family history. All patients received standard medical and dietary therapy prior to LT. The indications for LT were frequent metabolic decompensations in 4, elective in 2, and ALF in 1. The median age at LT was 2.4 years (range, 1.3-6.5). Five patients received 6 left lateral segment grafts, one a live unrelated donor left lateral segment as an APOLT graft, and one a cadaveric whole liver graft as APOLT. One child required retransplantation due to hepatic artery thrombosis. Graft and patient survival were 86% and 100%, respectively. Median follow-up is 3.1 years (range, 0.1-4.1), and the median age at follow-up is 5.5 years (range, 4.0-9.8). There have been no metabolic decompensations in 6 children, while 1 patient (with APOLT) developed asymptomatic hyperammonemia with no clinical or histological signs of liver injury, requiring additional medical therapy. Our medium-term experience following LT in citrullinemia is favorable, demonstrating a positive transformation of the clinical phenotype.

Percutaneous removal of biliary stones post‐liver transplant in a pediatric patient: Case report and review of the literature

“…Citrullinemia, also known as argininosuccinate synthetase deficiency, is an autosomal recessive genetic condition involving the urea cycle 1 . Classically, treatment options have included dietary management (restricting protein intake) and medical management (ammonia‐lowering drugs and arginine supplementation) 1 .…”

“…Citrullinemia, also known as argininosuccinate synthetase deficiency, is an autosomal recessive genetic condition involving the urea cycle 1 . Classically, treatment options have included dietary management (restricting protein intake) and medical management (ammonia‐lowering drugs and arginine supplementation) 1 . Despite these treatments, patients often still experience fluctuations in ammonia levels with episodes of acute hyperammonemia and typically have poor long‐term neurocognitive outcomes 1 .…”

“…Classically, treatment options have included dietary management (restricting protein intake) and medical management (ammonia‐lowering drugs and arginine supplementation) 1 . Despite these treatments, patients often still experience fluctuations in ammonia levels with episodes of acute hyperammonemia and typically have poor long‐term neurocognitive outcomes 1 . Liver transplantation is a viable treatment option for urea cycle defects, including neonatal citrullinemia, which corrects the urea cycle defect and eliminates the possibility of future hyperammonemia 1 .…”

“…Despite these treatments, patients often still experience fluctuations in ammonia levels with episodes of acute hyperammonemia and typically have poor long‐term neurocognitive outcomes 1 . Liver transplantation is a viable treatment option for urea cycle defects, including neonatal citrullinemia, which corrects the urea cycle defect and eliminates the possibility of future hyperammonemia 1 . In one study of seven children who received LT for neonatal citrullinemia, indications for transplantation were frequent metabolic decompensations (four patients), elective (two patients), and acute liver failure (one patient) 1 .…”

“…Liver transplantation is a viable treatment option for urea cycle defects, including neonatal citrullinemia, which corrects the urea cycle defect and eliminates the possibility of future hyperammonemia 1 . In one study of seven children who received LT for neonatal citrullinemia, indications for transplantation were frequent metabolic decompensations (four patients), elective (two patients), and acute liver failure (one patient) 1 . On follow‐up, six of these patients had no further metabolic decompensations, and one patient had an episode of asymptomatic hyperammonemia 1 .…”