|
|
鸟氨酸氨甲酰基转移酶缺乏症治疗的研究进展
|
Abstract:
鸟氨酸转氨甲酰酶缺乏症(OTCD)是一种遗传性的尿素循环障碍，死亡率高。它是一种代谢疾病，主要表现为高氨血症，血瓜氨酸降低及尿乳清酸升高。可出现癫痫、意识障碍、认知障碍等临床症状。药物治疗和透析可以降低血氨水平。肝移植可以提高患者的长期生存率，但不能逆转之前已经发生的神经系统损伤。基因治疗是一种新的研究方向，目前仍未运用于临床。本文就OTCD治疗的研究进展作一简要概述。
Ornithine transcarbamylase deficiency (OTCD) is a kind of genetic urea cycle disorder with a high mortality. It’s a metabolic disease manifested as hyperammonemia, decreased blood citrulline and increased urine orotic acids. Symptoms such as epilepsy, disturbance of consciousness, and cogni-tive impairment appear in OTCD. Drugs and dialysis can lower the blood ammonia level. Liver transplantation can improve the long-term survival rate of patients, but it cannot reverse the nervous system damage that has occurred before. Gene therapy is a research direction that has not yet been used in clinical practice. This article briefly summarizes the research progress of OTCD treatment.
| [1] | ？berle, J., Burlina, A., Chakrapani, A., Dixon, M., Karall, D., Lindner, M., Mandel, H., Martinelli, D., Pintos-Morell, G., Santer, R., Skouma, A., Servais, A., Tal, G., Rubio, V., Huemer, M. and Dionisi-Vici, C. (2019) Suggested Guidelines for the Diagnosis and Management of Urea Cycle Disorders: First Revision. Journal of Inherited Metabolic Disease, 42, 1192-1230. https://doi.org/10.1002/jimd.12100 |
| [2] | Wilcken, B. (2004) Problems in the Management of Urea Cy-cle Disorders. Molecular Genetics and Metabolism, 81, 86-91. https://doi.org/10.1016/j.ymgme.2003.10.016 |
| [3] | Leonard, J.V. and Morris, A.A. (2002) Urea Cycle Disorders. Seminars in Neonatology, 7, 27-35.
https://doi.org/10.1053/siny.2001.0085 |
| [4] | Summar, M.L., Dobbelaere, D., Brusilow, S. and Lee, B. (2008) Di-agnosis, Symptoms, Frequency and Mortality of 260 Patients with Urea Cycle Disorders from a 21-Year, Multicentre Study of Acute Hyperammonaemic Episodes. Acta Paediatrica, 97, 1420-1425. https://doi.org/10.1111/j.1651-2227.2008.00952.x |
| [5] | Msall, M., Batshaw, M.L., Suss, R., Brusilow, S.W. and Mellits, E.D. (1984) Neurologic Outcome in Children with Inborn Errors of Urea Synthesis. Outcome of Urea-Cycle Enzymopathies. New England Journal of Medicine, 310, 1500-1505. https://doi.org/10.1056/NEJM198406073102304 |
| [6] | Choi, J.H., Lee, B.H., Kim, J.H., Kim, G.H., Kim, Y.M., Cho, J., Cheon, C.K., Ko, J.M., Lee, J.H. and Yoo, H.W. (2015) Clinical Outcomes and the Mutation Spectrum of the OTC Gene in Patients with Ornithine Transcarbamylase Deficiency. Journal of Human Genetics, 60, 501-507. https://doi.org/10.1038/jhg.2015.54 |
| [7] | Boneh, A. (2014) Dietary Protein in Urea Cycle defects: How Much? Which? How? Molecular Genetics and Metabolism, 113, 109-112. https://doi.org/10.1016/j.ymgme.2014.04.009 |
| [8] | 中国妇幼保健协会儿童疾病和保健分会遗传代谢学组. 鸟氨酸氨甲酰转移酶缺乏症诊治专家共识[J]. 浙江大学学报(医学版), 2020, 49(5): 539-547. |
| [9] | Kido, J., Nakamura, K., Mitsubuchi, H., Ohura, T., Takayanagi, M., Matsuo, M., Yoshino, M., Shigematsu, Y., Yorifuji, T., Kasahara, M., Horikawa, R. and Endo, F. (2012) Long-Term Outcome and Intervention of Urea Cycle Disorders in Japan. Journal of Inherited Metabolic Disease, 35, 777-785. https://doi.org/10.1007/s10545-011-9427-0 |
| [10] | Nakamura, K., Kido, J., Matsumoto, S., Mitsubuchi, H. and Endo, F. (2016) Clinical Manifestations and Growth of Patients with Urea Cycle Disorders in Japan. Journal of Human Genetics, 61, 613-616.
https://doi.org/10.1038/jhg.2016.17 |
| [11] | Imoto, K., Tanaka, M., Goya, T., Aoyagi, T., Takahashi, M., Kurokawa, M., Tashiro, S., Kato, M., Kohjima, M. and Ogawa, Y. (2022) Corticosteroid Suppresses Urea-Cycle-Related Gene Ex-pressions in Ornithine Transcarbamylase Deficiency. BMC Gastroenterology, 22, Article No. 144. https://doi.org/10.1186/s12876-022-02213-0 |
| [12] | Gascon-Bayarri, J., Campdelacreu, J., Estela, J. and Re？é, R. (2015) Severe Hyperammonemia in Late-Onset Ornithine Transcarbamylase Deficiency Triggered by Steroid Admin-istration. Case Reports in Neurological Medicine, 2015, Article ID: 453752. https://doi.org/10.1155/2015/453752 |
| [13] | Wadzinski, J., Franks, R., Roane, D. and Bayard, M. (2007) Valproate-Associated Hyperammonemic Encephalopathy. The Journal of the American Board of Family Medicine, 20, 499-502. https://doi.org/10.3122/jabfm.2007.05.070062 |
| [14] | Molema, F., Gleich, F., Burgard, P., van der Ploeg, A.T., Summar, M.L., Chapman, K.A., Bari？, I., Lund, A.M., K？lker, S., Williams, M. and Additional individual contrib-utors from E-IMD (2019) Evaluation of Dietary Treatment And Amino acid Supplementation in Organic Acidurias and Urea-Cycle Disorders: On the Basis of Information from a European Multicenter Registry. Journal of Inherited Metabol-ic Disease, 42, 1162-1175.
https://doi.org/10.1002/jimd.12066 |
| [15] | Fujisawa, D., Mitsubuchi, H., Matsumoto, S., Iwai, M., Nakamura, K., Hoshide, R., Harada, N., Yoshino, M. and Endo, F. (2015) Early Intervention for Late-Onset Ornithine Transcarbamyl-ase Deficiency. Pediatrics International, 57, e1-e3. https://doi.org/10.1111/ped.12457 |
| [16] | Redant, S., Empain, A., Mugisha, A., Kamgang, P., Attou, R., Honoré, P.M. and De Bels, D. (2021) Management of Late Onset Urea Cycle Disorders—A Remaining Challenge for the Intensivist? Annals of Intensive Care, 11, Article No. 2. https://doi.org/10.1186/s13613-020-00797-y |
| [17] | Kim, I.K., Niemi, A.K., Krueger, C., Bonham, C.A., Concepcion, W., Cowan, T.M., Enns, G.M. and Esquivel, C.O. (2013) Liver Transplantation for Urea Cycle Disorders in Pediatric Patients: A Single-Center Experience. Pediatric Transplantation, 17, 158-167. https://doi.org/10.1111/petr.12041 |
| [18] | Morioka, D., Kasahara, M., Takada, Y., Shirouzu, Y., Taira, K., Sakamoto, S., Uryuhara, K., Egawa, H., Shimada, H. and Tanaka, K. (2005) 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. Liver Trans-plantation, 11, 1332-1342.
https://doi.org/10.1002/lt.20587 |
| [19] | 孙丽莹, 朱志军, 魏林, 杨艳玲, 曲伟, 曾志贵, 刘颖, 何恩辉, 张梁, 李晓莹, 张建蕊, 闫非易, 谭玉乐, 王君. 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. |
| [20] | Kido, J., Matsumoto, S., Mitsubuchi, H., Endo, F. and Nakamura, K. (2018) Early Liver Trans-plantation in Neonatal-Onset and Moderate Urea Cycle Disorders May Lead to Normal Neurodevelopment. Metabolic Brain Disease, 33, 1517-1523. https://doi.org/10.1007/s11011-018-0259-6 |
| [21] | Wakiya, T., Sanada, Y., Urahashi, T., Ihara, Y., Yamada, N., Okada, N., Ushijima, K., Otomo, S., Sakamoto, K., Murayama, K., Takayanagi, M., Hakamada, K., Yasuda, Y. and Mizuta, K. (2012) Impact of Enzyme Activity Assay on Indication in Liver Transplanta-tion for Ornithine Transcarbamylase Deficiency. Molecular Genetics and Metabolism, 105, 404-407. https://doi.org/10.1016/j.ymgme.2011.12.019 |
| [22] | Zhu, Z., Sun, L., Wei, L., Qu, W., Zeng, Z., Liu, Y., Zhang, L., He, E. and Wang, D. (2015) Liver Transplantation for the Treatment of Hyperammonemia Due to Urea Cycle Disorder: Report of Four Cases. Chinese Journal of Pediatrics, 53, 136-139. (In Chinese) |
| [23] | Nagasaka, H., Yorifuji, T., Egawa, H., Kikuta, H., Tanaka, K. and Kobayashi, K. (2001) Successful Living-Donor Liver Transplantation from an Asympto-matic Carrier Mother in Ornithine Transcarbamylase Deficiency. The Journal of Pediatrics, 138, 432-434. https://doi.org/10.1067/mpd.2001.111318 |
| [24] | Rahayatri, T.H., Uchida, H., Sasaki, K., Shigeta, T., Hirata, Y., Kanazawa, H., Mali, V., Fukuda, A., Sakamoto, S. and Kasahara, M. (2017) Hyperammonemia in Ornithine Transcar-bamylase-Deficient Recipients Following Living Donor Liver Transplantation from Heterozygous Carrier Donors. Pedi-atric Transplantation, 21, e12848.
https://doi.org/10.1111/petr.12848 |
| [25] | Wakiya, T., Sanada, Y., Urahashi, T., Ihara, Y., Yamada, N., Okada, N., Egami, S., Sakamoto, K., Murayama, K., Hakamada, K., Yasuda, Y. and Mizuta, K. (2012) Living Donor Liver Trans-plantation from an Asymptomatic Mother Who Was a Carrier for Ornithine Transcarbamylase Deficiency. Pediatric Transplantation, 16, E196-E200.
https://doi.org/10.1111/j.1399-3046.2012.01716.x |
| [26] | Ziogas, I.A., Wu, W.K., Matsuoka, L.K., Pai, A.K., Haf-berg, E.T., Gillis, L.A., Morgan, T.M. and Alexopoulos, S.P. (2021) Liver Transplantation in Children with Urea Cycle Disorders: The Importance of Minimizing Waiting Time. Liver Transplantation, 27, 1799-1810. https://doi.org/10.1002/lt.26186 |
| [27] | Enosawa, S., Horikawa, R., Yamamoto, A., Sakamoto, S., Shigeta, T., Nosa-ka, S., Fujimoto, J., Nakazawa, A., Tanoue, A., Nakamura, K., Umezawa, A., Matsubara, Y., Matsui, A. and Kasahara, M. (2014) Hepatocyte Transplantation Using a Living Donor Reduced Graft in a Baby with Ornithine Transcarbamylase Deficiency: A Novel Source of Hepatocytes. Liver Transplantation, 20, 391-393. https://doi.org/10.1002/lt.23800 |
| [28] | Qu, W., Wei, L., Zhu, Z.J., Sun, L.Y., Liu, Y. and Zeng, Z.G. (2019) Con-siderations for Use of Domino Cross-Auxiliary Liver Transplantation in Metabolic Liver Diseases: A Review of Case Studies. Transplantation, 103, 1916-1920. https://doi.org/10.1097/TP.0000000000002602 |
| [29] | Ng, H.I., Sun, L.Y. and Zhu, Z.J. (2018) Application of Graft-Derived Cell-Free DNA in Ornithine Transcarbamylase Deficiency Patient af-ter Living Donor Liver Transplantation: Two Case Reports. Medicine, 97, Article No. e13843.
https://doi.org/10.1097/MD.0000000000013843 |
| [30] | Yu, L., Rayhill, S.C., Hsu, E.K. and Landis, C.S. (2015) Liver Transplantation for Urea Cycle Disorders: Analysis of the United Network for Organ Sharing Database. Trans-plantation Proceedings, 47, 2413-2418.
https://doi.org/10.1016/j.transproceed.2015.09.020 |
| [31] | Kasahara, M., Sakamoto, S., Horikawa, R., Koji, U., Mi-zuta, K., Shinkai, M., Takahito, Y., Taguchi, T., Inomata, Y., Uemoto, S., Tatsuo, K. and Kato, S. (2014) Living Donor Liver Transplantation for Pediatric Patients with Metabolic Disorders: The Japanese Multicenter Registry. Pediatric Transplantation, 18, 6-15. https://doi.org/10.1111/petr.12196 |
| [32] | Lu, D., Han, F., Qiu, W., Zhang, H., Ye, J., Liang, L., Wang, Y., Ji, W., Zhan, X., Gu, X. and Han, L. (2020) Clinical and Molecular Characteristics of 69 Chinese Patients with Ornithine Transcarbamylase Deficiency. Orphanet Journal of Rare Diseases, 15, Article No. 340. https://doi.org/10.1186/s13023-020-01606-2 |
| [33] | Kido, J., Matsumoto, S., H？berle, J., Inomata, Y., Kasahara, M., Sakamoto, S., Horikawa, R., Tanemura, A., Okajima, H., Suzuki, T. and Nakamura, K. (2021) Role of Liver Transplan-tation in Urea Cycle Disorders: Report from a Nationwide Study in Japan. Journal of Inherited Metabolic Disease, 44, 1311-1322. https://doi.org/10.1002/jimd.12415 |
| [34] | Somanathan, S., Calcedo, R. and Wilson, J.M. (2020) Adeno-virus-Antibody Complexes Contributed to Lethal Systemic Inflammation in a Gene Therapy Trial. Molecular Therapy, 28, 784-793.
https://doi.org/10.1016/j.ymthe.2020.01.006 |
| [35] | Deakin, C.T., Alexander, I.E. and Kerridge, I. (2009) Accepting Risk in Clinical Research: Is the Gene Therapy Field Becoming Too Risk-Averse? Molecular Therapy, 17, 1842-1848. https://doi.org/10.1038/mt.2009.223 |
| [36] | De Sabbata, G., Boisgerault, F., Guarnaccia, C., Iaconcig, A., Bortolussi, G., Collaud, F., Ronzitti, G., Sola, M.S., Vidal, P., Rouillon, J., Charles, S., Nicastro, E., D’Antiga, L., Ilyinskii, P., Mingozzi, F., Kishimoto, T.K. and Muro, A.F. (2020) Long-Term Correction of Ornithine Transcarbamylase Deficiency in Spf-Ash Mice with a Translationally Optimized AAV Vector. Molecular Therapy—Methods & Clinical Development, 20, 169-180.
https://doi.org/10.1016/j.omtm.2020.11.005 |
| [37] | Baruteau, J., Cunningham, S.C., Yilmaz, B.S., Perocheau, D.P., Eaglestone, S., Burke, D., Thrasher, A.J., Waddington, S.N., Lisowski, L., Alexander, I.E. and Gissen, P. (2021) Safety and Efficacy of an Engineered Hepatotropic AAV Gene Therapy for Ornithine Transcarbamylase Deficiency in Cyno-molgus Monkeys. Molecular Therapy—Methods & Clinical Development, 23, 135-146. https://doi.org/10.1016/j.omtm.2021.09.005 |
| [38] | Zabulica, M., Srinivasan, R.C., Akcakaya, P., Allegri, G., Bestas, B., Firth, M., Hammarstedt, C., Jakobsson, T., Jakobsson, T., Ellis, E., Jorns, C., Makris, G., Scherer, T., Rimann, N., van Zuydam, N.R., Gramignoli, R., Forsl？w, A., Engberg, S., Maresca, M., Rooyackers, O., Th？ny, B., H？berle, J., Rosen, B. and Strom, S.C. (2021) Correction of a Urea Cycle Defect after ex Vivo Gene Editing of Human Hepatocytes. Molecular Therapy, 29, 1903-1917.
https://doi.org/10.1016/j.ymthe.2021.01.024 |
| [39] | Prieve, M.G., Harvie, P., Monahan, S.D., Roy, D., Li, A.G., Blevins, T.L., Paschal, A.E., Waldheim, M., Bell, E.C., Galperin, A., Ella-Menye, J.R. and Houston, M.E. (2018) Tar-geted mRNA Therapy for Ornithine Transcarbamylase Deficiency. Molecular Therapy, 26, 801-813. https://doi.org/10.1016/j.ymthe.2017.12.024 |
| [40] | Timmer, C., Davids, M., Nieuwdorp, M., Levels, J.H.M., Langendonk, J.G., Breederveld, M., Ahmadi Mozafari, N. and Langeveld, M. (2021) Differences in Faecal Microbiome Composition between Adult Patients with UCD and PKU and Healthy Control Subjects. Molecular Genetics and Metab-olism Reports, 29, Article ID: 100794.
https://doi.org/10.1016/j.ymgmr.2021.100794 |
