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造血干细胞移植治疗Omenn综合征1例
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Abstract:
目的：探讨造血干细胞移植治疗Omenn综合征的移植经验，提高临床对Omenn综合征治疗的认识。方法：回顾性分析2020年武汉儿童医院收治的1例重症Omenn综合征患儿的临床资料。结果：男性患儿，1岁2月，主要表现为反复呼吸道感染伴脱屑性皮疹，肝大，严重的B淋巴细胞减少，经全外显子测序发现RAG1基因存在c.2209(exon2)C > T及c.2095(exon2)C > T复合杂合变异，确诊为Omenn综合征，行异基因造血干细胞移植，移植后 + 19 d出现急性移植物抗宿主病，最终移植后 + 47 d因循环衰竭死亡。结论：Omenn综合征是一种罕见的严重联合免疫缺陷病，通过基因检测确诊，该病病死率高，目前最主要的治疗方式为造血干细胞移植，早期诊断并在感染前进行移植有望减少移植相关并发症，是移植成功的关键。
Objective: To explore the experience of hematopoietic stem cell transplantation in the treatment of Omenn syndrome, and to improve the clinical understanding of OS treatment. Methods: The clinical data of a child with severe Omenn syndrome admitted to Wuhan Children’s Hospital in 2020 were retrospectively analyzed. Results: The male child, aged 1 year and 2 months, was mainly character-ized by repeated respiratory tract infection with desquamation rash, large liver and severe B lym-phocyte reduction. After the whole exon sequencing, it was found that RAG1 gene had c.2209(exon2)C > T and c.2095(exon2)C > T compound heterozygosity, and was diagnosed as Omenn syndrome. After allogeneic hematopoietic stem cell transplantation, acute graft-versus-host disease appeared +19 days after transplantation, and finally died of circulatory failure +47 days af-ter transplantation. Conclusion: Omenn syndrome is a rare severe combined immunodeficiency disease, which is diagnosed by genetic testing with high mortality. At present, the main treatment is hematopoietic stem cell transplantation. Early diagnosis and transplantation before infection are expected to reduce the complications related to transplantation, which is the key to successful transplantation.
| [1] | Omenn, G.S. (1965) Familial Reticuloendotheliosis with Eosinophilia. The New England Journal of Medicine, 273, 427-432. https://doi.org/10.1056/NEJM196508192730806 |
| [2] | Dorsey, M.J. and Puck, J.M. (2019) Newborn Screening for Severe Combined Immunodeficiency in the United States: Lessons Learned. Immunology and Allergy Clinics of North America, 39, 1-11.
https://doi.org/10.1016/j.iac.2018.08.002 |
| [3] | 高洪杰, 刘华卫. 1例Omenn综合征患儿的临床特点及基因突变[J]. 山东大学学报(医学版), 2019, 57(3): 120-124. |
| [4] | Cutts, L., Bakshi, A., Walsh, M., et al. (2021) Diagnosing Omenn Syndrome. Pediatric Dermatology, 38, 541-543.
https://doi.org/10.1111/pde.14401 |
| [5] | Tallar, M. and Routes, J. (2020) Omenn Syndrome Identified by Newborn Screening. Clinics in Perinatology, 47, 77-86. https://doi.org/10.1016/j.clp.2019.09.004 |
| [6] | Secord, E. and Hartog, N.L. (2022) Review of Treatment for Adenosine Deaminase Deficiency (ADA) Severe Combined Immunodeficiency (SCID). Therapeutics and Clinical Risk Management, 18, 939-944.
https://doi.org/10.2147/TCRM.S350762 |
| [7] | 袁建涛, 雷婷. Omenn综合征临床表型及分子诊断[J]. 临床儿科杂志, 2018, 36(2): 117-120. |
| [8] | Estebanez, A., Verdu-Amoros, J., Silva, E., et al. (2021) A Heterozygous Mutation in the RAG2 Gene with Cutaneous and Systemic Manifestations Partially Resembling Omenn Syndrome. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 19, 906-908. https://doi.org/10.1111/ddg.14383 |
| [9] | Valeri, L., Lugli, L., Iughetti, L., et al. (2022) Omenn Syndrome Due to RAG1 Mutation Presenting with Nonimmune Hydrops Fe-talis in Two Siblings. Pediatrics, 149, e2021052411. https://doi.org/10.1542/peds.2021-052411 |
| [10] | Benhsaien, I., Essadssi, S., Elkhattabi, L., et al. (2021) Omenn Syndrome Caused by a Novel Homozygous Mutation in Recombination Activating Gene 1. Immunobiology, 226, Article ID: 152090.
https://doi.org/10.1016/j.imbio.2021.152090 |
| [11] | Marrella, V., Maina, V. and Villa, A. (2011) Omenn Syndrome Does Not Live by V(D)J Recombination Alone. Current Opinion in Allergy and Clinical Immunology, 11, 525-531. https://doi.org/10.1097/ACI.0b013e32834c311a |
| [12] | Sharapova, S.O., Guryanova, I.E., Pashchenko, O.E., et al. (2016) Molecular Characteristics, Clinical and Immunologic Manifestations of 11 Children with Omenn Syndrome in East Slavs (Russia, Belarus, Ukraine). Journal of Clinical Immunology, 36, 46-55. https://doi.org/10.1007/s10875-015-0216-7 |
| [13] | Slatter, M.A. and Gennery, A.R. (2022) Advances in the Treat-ment of Severe Combined Immunodeficiency. Clinical Immunology, 242, Article ID: 109084. https://doi.org/10.1016/j.clim.2022.109084 |
| [14] | Fischer, A. (2022) Gene Therapy for Inborn Errors of Immunity: Past, Present and Future. Nature Reviews Immunology.
https://doi.org/10.1038/s41577-022-00800-6 |
| [15] | Currier, R. and Puck, J.M. (2021) SCID Newborn Screening: What We’ve Learned. Journal of Allergy and Clinical Immunology, 147, 417-426. https://doi.org/10.1016/j.jaci.2020.10.020 |
