Liver transplantation for urea cycle disorders in pediatric patients: A single-center experience Kim IK, Niemi A-K, Krueger C, Bonham CA, Concepcion W, Cowan TM, Enns GM, Esquivel CO. Liver transplantation for urea cycle disorders in pediatric patients: A single-center experience. Abstract: LT has emerged as a surgical treatment for UCDs. We hypothesize that LT can be safely and broadly utilized in the pediatric population to effectively prevent hyperammonemic crises and potentially improve neurocognitive outcomes. 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 July 2001 and May 2012. A total of 23 patients with UCD underwent LT at a mean age of 3.4 yr. Fifteen (65%) patients received a whole-liver graft, seven patients (30%) received a reduced- size graft, and one patient received a living donor graft. Mean five-yr patient survival was 100%, and allograft survival was 96%. Mean peak blood ammonia (NH 3 ) at presentation was 772 lmol/L (median 500, range 178–2969, normal <30–50). After transplantation, there were no episodes of hyperammonemia. Eleven patients were diagnosed with some degree of developmental delay before transplantation, which remained stable or improved after transplantation. Patients without developmental delay before transplantation maintained their cognitive abilities at long-term follow-up. LT was associated with the eradication of hyperammonemia, removal of dietary restrictions, and potentially improved neurocognitive development. Long-term follow-up is underway to evaluate whether LT at an early age (<1 yr) will attain improved neurodevelopmental outcomes. Irene K. Kim 1 , Anna-Kaisa Niemi 2 , Casey Krueger 3 , Clark A. Bonham 1 , Waldo Concepcion 1 , Tina M. Cowan 4 , Gregory M. Enns 2 and Carlos O. Esquivel 1 1 Division of Abdominal Transplantation, Department of Surgery, Stanford University, Stanford, CA, USA, 2 Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA, USA, 3 Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University, Stanford, CA, USA, 4 Department of Pathology, Stanford University, Stanford, CA, USA Key words: urea cycle disorders – pediatric liver transplantation Carlos O. Esquivel, MD, PhD, Division of Abdominal Transplantation, Stanford University School of Medicine, 300 Pasteur Dr, MC 5730, Stanford, CA 94305, USA Tel.: +1 650 498 5689 Fax: +1 650 498 5690 E-mail: esquivel@stanford.edu Accepted for publication 14 November 2012 UCDs encompass a set of metabolic disorders caused by enzymatic disruption of the urea cycle pathway that transforms nitrogen to urea for excretion from the body (Fig. 1). There are six UCDs: NAGS deficiency, CPS I deficiency, OTC deficiency, ASS deficiency (also known as classic citrullinemia), ASL deficiency, and arginase defi- ciency. The incidence of these disorders ranges from 1:8200 births in the United States to 1:30 000 live births (1–3). Of the six disorders, only OTC deficiency is an X-linked disorder, while the rest are inherited in an autosomal reces- sive pattern. Symptoms range from asymptom- atic adults to fatal neonatal hyperammonemia resulting in serious neurological injury, perma- nent neurological damage, and poor neurodevel- opmental outcome, especially in neonatal-onset cases (4, 5). Medical management has been aimed at early detection, protein restriction, administration of ammonia scavengers, and dial- ysis of ammonia during crises (6–8). In UCDs, the conversion of ammonia to urea is dependent on six enzymes located in liver. LT has emerged as a surgical treatment for UCDs in patients who have failed medical management and who are at risk of recurrent hyperammone- mia. LT restores the metabolic defect and results Abbreviations: ADHD, attention-deficit/hyperactivity dis- order; ASL, argininosuccinate lyase; ASS, argininosuccinate synthetase; CPS I, carbamyl phosphate synthetase I; LD, learning disability; LOS, length of stay; LRLT, living related liver transplant; LT, liver transplantation; NAGS, N-acetyl-glutamate synthetase; OLT, orthotopic liver trans- plant; OPTN, Organ Procurement and Transplant Net- work; OTC, ornithine transcarbamylase; PELD, pediatric end-stage liver disease; PTLD, post-transplant lymphoproli- ferative disorder; UCDs, urea cycle disorders. 158 Pediatr Transplantation 2013: 17: 158–167 © 2013 John Wiley & Sons A/S. Pediatric Transplantation DOI: 10.1111/petr.12041