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J Zhejiang Univ (Med Sci)
Consensus on diagnosis and treatment of ornithine transcarbamylase deficiency
Division of Genetics and Metabolism, Child Diseases and Health Care Branch, Chinese Association for Maternal and Child Health
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Abstract  Ornithine transcarbamylase deficiency(OTCD)is a most common urea cycle disorder. It is a X-link inherited disorder caused by OTC gene mutation that in turn leads to reduction or loss of OTC enzyme activity. Its onset time is related to the lack of enzyme activity. Patients with neonatal onset usually have complete absence of OTC enzyme activity, which is mainly associated with male semi-zygotic mutations; and the disease progresses rapidly with high mortality rates. Patients with late onset vary greatly in onset age and clinical manifestations; the course of disease can be progressive or intermittent. The acute attack mainly manifests neuropsychiatric symptoms accompanied by digestive symptoms and liver function damage or even acute liver failure. Elevated blood ammonia is the main biochemical indicator of OTCD patients. This biochemical phenotype (increased glutamine and decreased citrulline in blood, increased orotic acid in urine) is classical for OTCD patients. Genetic testing of OTC gene is an important basis for OTCD diagnosis. The goal of treatment is to minimize the neurological damage caused by hyperammonemia while ensuring the nutritional needs for patient development. For patients with poor response to medication and diet, liver transplantation is recommended under the condition of stable metabolic state and absence of severe neurological damage. During long-term treatment, physical growth indicators, nutrition status, liver function and blood ammonia and amino acids should be regularly monitored. This consensus is conducive to standardize the diagnosis and treatment of OTCD, improve the prognosis, reduce the mortality and disability of patients.

Key wordsOrnithine carbamoyltransferase deficiency disease      Hyperammonemia      Diagnosis      Treatment     
Received: 19 December 2019      Published: 29 May 2020
CLC:  R41  
Cite this article:

Division of Genetics and Metabolism, Child Diseases and Health Care Branch, Chinese Association for Maternal and Child Health. Consensus on diagnosis and treatment of ornithine transcarbamylase deficiency. J Zhejiang Univ (Med Sci), 0, 0(0): 7-0.

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关键词: 鸟氨酸氨甲酰转移酶缺乏症,  高氨血症,  诊断,  治疗 
[1] 顾学范. 临床遗传代谢病[M]. 北京:人民卫生出版社, 2015.GU Xuefan. Clinical genetic and metabolic diseases[M]. Beijing:People's Medical Publishing House, 2015. (in Chinese)
[2] LICHTER-KONECKI U, CALDOVIC L, MORIZONO H, et al. Ornithine transcarbamylase deficiency[A]//ADAM M P, ARDINGER H H, PAGON R A, et al. Gene Reviews. Seattle (WA):University of Washington, 1993.
[3] WILCKEN B. Problems in the management of urea cycle disorders[J]. Mol Genet Metab, 2004, 81 Suppl 1:S86-91. DOI:10.1016/j.ymgme.2003.10.016.
[4] SUMMAR M L, KOELKER S, FREEDENBERG D, et al. The incidence of urea cycle disorders[J]. Mol Genet Metab, 2013,110(1-2):179-180. DOI:10.1016/j.ymgme.2013.07.008.
[5] DIONISI-VICI C, RIZZO C, BURLINA A B, et al. Inborn errors of metabolism in the Italian pediatric population:a national retrospective survey[J]. J Pediatr, 2002,140(3):321-327. DOI:10.1067/mpd.2002.122394.
[6] KIDO J, NAKAMURA K, MITSUBUCHI H, et al. Long-term outcome and intervention of urea cycle disorders in Japan[J]. J Inherit Metab Dis, 2012,35(5):777-785. DOI:10.1007/s10545-011-9427-0.
[7] 杨艳玲, 孙芳, 钱宁, 等. 尿素循环障碍的临床和实验室筛查研究[J]. 中华儿科杂志, 2005, 43(5):331-334. DOI:10.3760/j.issn:0578-1310.2005.05.003. YANG Yanling,SUN Fang,QIAN Ning,et al. Clinical and laboratory screening studies on urea cycle defects[J]. Chinese Journal of Pediatrics, 2005, 43(5):331-334. DOI:10.3760/j.issn:0578-1310.2005.05.003. (in Chinese)
[8] HÄBERLE J, BURLINA A, CHAKRAPANI A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders:First revision[J]. J Inherit Metab Dis, 2019,42(6):1192-1230. DOI:10.1002/jimd.12100.
[9] TUCHMAN M, LEE B, LICHTER-KONECKI U, et al. Cross-sectional multicenter study of patients with urea cycle disorders in the United States[J]. Mol Genet Metab, 2008,94(4):397-402. DOI:10.1016/j.ymgme.2008.05.004.
[10] SINGH R H. Nutritional management of patients with urea cycle disorders[J]. J Inherit Metab Dis, 2007,30(6):880-887. DOI:10.1007/s10545-007-0718-4.
[11] BONEH A. Dietary protein in urea cycle defects:How much? Which? How?[J]. Mol Genet Metab, 2014,113(1-2):109-112. DOI:10.1016/j.ymgme.2014.04.009.
[12] NAKAMURA K, KIDO J, MITSUBUCHI H, et al. Diagnosis and treatment of urea cycle disorder in Japan[J]. Pediatr Int, 2014,56(4):506-509. DOI:10.1111/ped.12439.
[13] HÄBERLE J, BODDAERT N, BURLINA A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders[J]. Orphanet J Rare Dis, 2012,7:32. DOI:10.1186/1750-1172-7-32.
[14] MORRIS S M JR. Regulation of enzymes of the urea cycle and arginine metabolism[J]. Annu Rev Nutr, 2002,22:87-105. DOI:10.1146/annurev.nutr.22.110801.140547.
[15] CALDOVIC L, ABDIKARIM I, NARAIN S, et al. Genotype-phenotype correlations in ornithine transcarbamylase deficiency:a mutation update[J]. J Genet Genomics, 2015,42(5):181-194. DOI:10.1016/j.jgg.2015.04.003.
[16] BRAISSANT O. Current concepts in the pathogenesis of urea cycle disorders[J]. Mol Genet Metab, 2010,100 Suppl 1:S3-3S12. DOI:10.1016/j.ymgme.2010.02.010.
[17] POSSET R, GARBADE S F, BOY N, et al. Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders-A successful strategy for clinical research of rare diseases[J]. J Inherit Metab Dis, 2019,42(1):93-106. DOI:10.1002/jimd.12031.
[18] BURGARD P, KÖLKER S, HAEGE G, et al. Neonatal mortality and outcome at the end of the first year of life in early onset urea cycle disorders——review and meta-analysis of observational studies published over more than 35 years[J]. J Inherit Metab Dis, 2016,39(2):219-229. DOI:10.1007/s10545-015-9901-1.
[19] GORDON N. Ornithine transcarbamylase deficiency:a urea cycle defect[J]. Eur J Paediatr Neurol, 2003,7(3):115-121. DOI:10.1016/s1090-3798(03)00040-0.
[20] NASSOGNE M C, HÉRON B, TOUATI G, et al. Urea cycle defects:management and outcome[J]. J Inherit Metab Dis, 2005,28(3):407-414. DOI:10.1007/s10545-005-0303-7.
[21] 王海军,李东晓,王琪,等.一家系3例鸟氨酸氨甲酰基转移酶缺乏症的临床特征及基因分析[J]. 中华实用儿科临床杂志,2018, 33(13):1028-1029. DOI:10.3760/cma.j.issn.2095-428X.2018.13.015. WANG Haijun, LI Dongxiao, WAN Qi et al. Clinical features of 3 patients from 1 family affected by ornithine aminotransferase deficiency and gene analysis[J]. Chinese Journal of Applied Clinical Pediatrics, 2018, 33(13):1028-1029. DOI:10.3760/cma.j.issn.2095-428X. 2018.13.015. (in Chinese)
[22] MARTÍN-HERNÁNDEZ E, ALDÁMIZ-ECHEVARRÍA L, CASTEJÓN-PONCE E, et al. Urea cycle disorders in Spain:an observational, cross-sectional and multicentric study of 104 cases[J]. Orphanet J Rare Dis, 2014,9:187. DOI:10.1186/s13023-014-0187-4.
[23] GALLAGHER R C, LAM C, WONG D, et al. Significant hepatic involvement in patients with ornithine transcarbamylase deficiency[J]. J Pediatr, 2014,164(4):720-725.e6. DOI:10.1016/j.jpeds.2013.12.024.
[24] LEONARD J V, MORRIS A A. Urea cycle disorders[J]. Semin Neonatol, 2002,7(1):27-35. DOI:10.1053/siny.2001.0085.
[25] BRASSIER A, GOBIN S, ARNOUX J B, et al. Long-term outcomes in Ornithine Transcarbamylase deficiency:a series of 90 patients[J]. Orphanet J Rare Dis, 2015,10:58. DOI:10.1186/s13023-015-0266-1.
[26] SHAO Y, JIANG M, LIN Y, et al. Clinical and mutation analysis of 24 Chinese patients with ornithine transcarbamylase deficiency[J]. Clin Genet, 2017,92(3):318-322. DOI:10.1111/cge.13004.
[27] CAVICCHI C, MALVAGIA S, LA MARCA G, et al. Hypocitrullinemia in expanded newborn screening by LC-MS/MS is not a reliable marker for ornithine transcarbamylase deficiency[J]. J Pharm Biomed Anal, 2009, 49(5):1292-1295. DOI:10.1016/j.jpba.2009.03.001.
[28] 周平, 宋元宗, 肖昕, 等. 鸟氨酸氨甲酰基转移酶缺陷病1例[J]. 实用儿科临床杂志, 2006, 21(8):459, 462. DOI:10.3969/j.issn.1003-515X.2006.08.029. ZHOU Ping, SONG Yuanzong, XIAO Xin, et al. A case of ornithine transcarbamylase deficiency[J]. Journal of Applied Clinical Pediatrics, 2006, 21(8):459, 462. DOI:10.3969/j.issn.1003-515X.2006.08.029. (in Chinese)
[29] 龚珠文, 韩连书, 叶军, 等. 多重连接探针扩增技术诊断鸟氨酸氨甲酰转移酶缺乏症五例[J]. 中华儿科杂志, 2016, 54(6):437-440. DOI:10.3760/cma.j.issn.0578-1310.2016.06.010. GONG Zhuwen, HAN Lianshu, YE Jun, et al. Applying multiple probe amplification in the diagnosis of 5 cases with ornithine transcarbamylase deficiency[J]. Chinese Journal of Pediatrics, 2016, 54(6):437-440. DOI:10.3760/cma.j.issn.0578-1310.2016.06.010. (in Chinese)
[30] SHCHELOCHKOV O A, LI F Y, GERAGHTY M T, et al. High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide array CGH[J]. Mol Genet Metab, 2009,96(3):97-105. DOI:10.1016/j.ymgme.2008.11.167.
[31] ENGEL K, NUOFFER J M, MÜHLHAUSEN C, et al. Analysis of mRNA transcripts improves the success rate of molecular genetic testing in OTC deficiency[J]. Mol Genet Metab, 2008,94(3):292-297. DOI:10.1016/j.ymgme.2008.03.009.
[32] TAKANASHI J, BARKOVICH A J, CHENG S F, et al. Brain MR imaging in neonatal hyperammonemic encephalopathy resulting from proximal urea cycle disorders[J]. AJNR Am J Neuroradiol, 2003,24(6):1184-1187.
[33] PACHECO-COLÓN I, FRICKE S, VANMETER J, et al. Advances in urea cycle neuroimaging:Proceedings from the 4th International Symposium on urea cycle disorders, Barcelona, Spain, September 2013[J]. Mol Genet Metab, 2014,113(1-2):118-126. DOI:10.1016/j.ymgme.2014.05.005.
[34] BACHMANN C. Outcome and survival of 88 patients with urea cycle disorders:a retrospective evaluation[J]. Eur J Pediatr, 2003,162(6):410-416. DOI:10.1007/s00431-003-1188-9.
[35] ADAM S, ALMEIDA M F, ASSOUN M, et al. Dietary management of urea cycle disorders:European practice[J]. Mol Genet Metab, 2013,110(4):439-445. DOI:10.1016/j.ymgme.2013.09.003.
[36] World Health Organization. Protein and amino acid requirement in human nutrition[EB/OL]. (2007).
[37] KIM I K, NIEMI A K, KRUEGER C, et al. Liver transplantation for urea cycle disorders in pediatric patients:a single-center experience[J]. Pediatr Transplant, 2013,17(2):158-167. DOI:10.1111/petr.12041.
[38] MORIOKA D, KASAHARA M, TAKADA Y, et al. Current role of liver transplantation for the treatment of urea cycle disorders:a review of the worldwide English literature and 13 cases at Kyoto University[J]. Liver Transpl, 2005, 11(11):1332-1342. DOI:10.1002/lt.20587.
[39] 孙丽莹,朱志军,魏林,等. 肝移植治疗儿童遗传代谢性疾病42例[J]. 中华器官移植杂志, 2017, 38(6):337-342. DOI:10.3760/cma.j.issn.0254-1785.2017.06.004. SUN Liying, ZHU Zhijun, WEI Lin, et al. Pediatric liver transplantation for metabolic liver diseases report of 42 children[J]. Chinese Journal of Organ Transplantation, 2017, 38(6):337-342. DOI:10.3760/cma.j.issn.0254-1785.2017.06.004. (in Chinese)
[40] BUSUTTIL A A, GOSS J A, SEU P, et al. The role of orthotopic liver transplantation in the treatment of ornithine transcarbamylase deficiency[J]. Liver Transpl Surg, 1998, 4(5):350-354. DOI:10.1002/lt.500040504.
[41] KRIVITZKY L, BABIKIAN T, LEE H S, et al. Intellectual, adaptive, and behavioral functioning in children with urea cycle disorders[J]. Pediatr Res, 2009,66(1):96-101. DOI:10.1203/PDR.0b013e3181a27a16.
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