{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T14:35:59Z","timestamp":1782570959955,"version":"3.54.5"},"reference-count":17,"publisher":"American Academy of Pediatrics (AAP)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,10,1]]},"abstract":"<jats:p>Urea cycle defects (UCDs) typically present with hyperammonemia, the duration and peak levels of which are directly related to the neurologic outcome. Liver transplantation can cure the underlying defect for some conditions, but the preexisting neurologic status is a major factor in the final outcome. Multicenter data indicate that most of the children who receive transplants remain significantly neurologically impaired. We wanted to determine whether aggressive metabolic management of ammonia levels after early referral\/transfer to a metabolism center and early liver transplantation would result in better neurologic outcomes. We report on 5 children with UCDs, ie, 2 male patients with X-linked ornithine transcarbamylase deficiency and 2 male patients with carbamoyl phosphate synthase deficiency, all of whom had neonatal presentations and underwent orthotopic liver transplantation before 1 year of age, and 1 female patient with partial X-linked ornithine transcarbamylase deficiency that was intractable to medical therapy, who underwent transplantation at 35 months of age. Developmental testing with the Griffiths scale was performed on 3 occasions each, 12 months apart, up to 45 months after transplantation. Full-scale indices for 3 children who underwent early transplantation showed average developmental quotients of 67. All 5 children had metabolic cures. There were no deaths (30-month survival rate: 100%). One child is currently listed for repeat transplantation because of bile duct stenosis and cirrhosis. We conclude that early liver transplantation and aggressive metabolic management improve early neurologic outcomes for children with UCDs, but longer follow-up monitoring is needed.<\/jats:p>","DOI":"10.1542\/peds.2004-0198","type":"journal-article","created":{"date-parts":[[2004,10,13]],"date-time":"2004-10-13T18:57:26Z","timestamp":1097693846000},"page":"e523-e526","source":"Crossref","is-referenced-by-count":64,"title":["Developmental Outcomes With Early Orthotopic Liver Transplantation for Infants With Neonatal-Onset Urea Cycle Defects and a Female Patient With Late-Onset Ornithine Transcarbamylase Deficiency"],"prefix":"10.1542","volume":"114","author":[{"given":"Kim L.","family":"McBride","sequence":"first","affiliation":[{"name":"Molecular and Human Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Miller","sequence":"additional","affiliation":[{"name":"Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Carter","sequence":"additional","affiliation":[{"name":"Molecular and Human Genetics"},{"name":"Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saul","family":"Karpen","sequence":"additional","affiliation":[{"name":"Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Goss","sequence":"additional","affiliation":[{"name":"Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Lee","sequence":"additional","affiliation":[{"name":"Molecular and Human Genetics"},{"name":"Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2004,10,1]]},"reference":[{"key":"2021120906081404500_R1","unstructured":"Brusilow SW, Horwich AL. Urea cycle enzymes. In: Scriver CR, Beaudet AL, Valle D, Sly WS, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001:1909\u20131964"},{"key":"2021120906081404500_R2","doi-asserted-by":"crossref","unstructured":"Uchino T, Endo F, Matsuda I. Neurodevelopmental outcome of long-term therapy of urea cycle disorders in Japan. J Inherited Metab Dis.\u20081998;21(suppl 1):151\u2013159","DOI":"10.1023\/A:1005374027693"},{"key":"2021120906081404500_R3","doi-asserted-by":"crossref","unstructured":"Msall M, Monahan PS, Chapanis N, Batshaw ML. Cognitive development in children with inborn errors of urea synthesis. Acta Paediatr Jpn.\u20081988;30:435\u2013441","DOI":"10.1111\/j.1442-200X.1988.tb02534.x"},{"key":"2021120906081404500_R4","doi-asserted-by":"crossref","unstructured":"Msall M, Batshaw ML, Suss R, Brusilow SW, Mellits ED. Neurologic outcome in children with inborn errors of urea synthesis: outcome of urea-cycle enzymopathies. N Engl J Med.\u20081984;310:1500\u20131505","DOI":"10.1056\/NEJM198406073102304"},{"key":"2021120906081404500_R5","doi-asserted-by":"crossref","unstructured":"Maestri NE, Clissold D, Brusilow SW. Neonatal onset ornithine transcarbamylase deficiency: a retrospective analysis. J Pediatr.\u20081999;134:268\u2013272","DOI":"10.1016\/S0022-3476(99)70448-8"},{"key":"2021120906081404500_R6","doi-asserted-by":"crossref","unstructured":"Whitington PF, Alonso EM, Boyle JT, et al. Liver transplantation for the treatment of urea cycle disorders. J Inherited Metab Dis.\u20081998;21(suppl 1):112\u2013118","DOI":"10.1023\/A:1005317909946"},{"key":"2021120906081404500_R7","doi-asserted-by":"crossref","unstructured":"Lee B, Goss J. Long-term correction of urea cycle disorders. J Pediatr.\u20082001;138(suppl):S62\u2013S71","DOI":"10.1067\/mpd.2001.111838"},{"key":"2021120906081404500_R8","doi-asserted-by":"crossref","unstructured":"Scaglia F, Zheng Q, O\u2019Brien WE, et al. An integrated approach to the diagnosis and prospective management of partial ornithine transcarbamylase deficiency. Pediatrics.\u20082002;109:150\u2013152","DOI":"10.1542\/peds.109.1.150"},{"key":"2021120906081404500_R9","unstructured":"Griffiths R. The Ability of Babies. London, United Kingdom: University of London Press; 1954"},{"key":"2021120906081404500_R10","doi-asserted-by":"crossref","unstructured":"Luiz DM, Foxcroft CD, Stewart R. The construct validity of the Griffiths Scales of Mental Development. Child Care Health Dev.\u20082001;27:73\u201383","DOI":"10.1046\/j.1365-2214.2001.00158.x"},{"key":"2021120906081404500_R11","doi-asserted-by":"crossref","unstructured":"Todo S, Starzl TE, Tzakis A, et al. Orthotopic liver transplantation for urea cycle enzyme deficiency. Hepatology.\u20081992;15:419\u2013422","DOI":"10.1002\/hep.1840150311"},{"key":"2021120906081404500_R12","doi-asserted-by":"crossref","unstructured":"Saudubray JM, Touati G, Delonlay P, et al. Liver transplantation in urea cycle disorders. Eur J Pediatr.\u20081999;158(suppl 2):S55\u2013S59","DOI":"10.1007\/PL00014323"},{"key":"2021120906081404500_R13","unstructured":"Jan D, Poggi F, Jouvet P, et al. Definitive cure of hyperammonemia by liver transplantation in urea cycle defects: report of three cases. Transplant Proc.\u20081994;26:188"},{"key":"2021120906081404500_R14","doi-asserted-by":"crossref","unstructured":"Hasegawa T, Tzakis AG, Todo S, et al. Orthotopic liver transplantation for ornithine transcarbamylase deficiency with hyperammonemic encephalopathy. J Pediatr Surg.\u20081995;30:863\u2013865","DOI":"10.1016\/0022-3468(95)90766-1"},{"key":"2021120906081404500_R15","doi-asserted-by":"crossref","unstructured":"Otte JB. History of pediatric liver transplantation: where are we coming from? Where do we stand?Pediatr Transplant.\u20082002;6:378\u2013387","DOI":"10.1034\/j.1399-3046.2002.01082.x"},{"key":"2021120906081404500_R16","doi-asserted-by":"crossref","unstructured":"Holmes RD, Sokol RJ. Epstein-Barr virus and post-transplant lymphoproliferative disease. Pediatr Transplant.\u20082002;6:456\u2013464","DOI":"10.1034\/j.1399-3046.2002.02043.x"},{"key":"2021120906081404500_R17","doi-asserted-by":"crossref","unstructured":"Horslen SP, McCowan TC, Goertzen TC, et al. Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder. 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