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中华妇幼临床医学杂志(电子版) ›› 2019, Vol. 15 ›› Issue (04) : 403 -409. doi: 10.3877/cma.j.issn.1673-5250.2019.04.008

所属专题: 文献

论著

范可尼贫血诊治分析并文献复习
张婷1, 王华1,(), 唐军1, 母得志1   
  1. 1. 四川大学华西第二医院新生儿科、出生缺陷与相关妇儿疾病教育部重点实验室,成都 610041
  • 收稿日期:2019-01-07 修回日期:2019-05-05 出版日期:2019-08-01
  • 通信作者: 王华

Diagnosis and treatment of Fanconi anemia and literature review

Ting Zhang1, Hua Wang1,(), Jun Tang1, Dezhi Mu1   

  1. 1. Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2019-01-07 Revised:2019-05-05 Published:2019-08-01
  • Corresponding author: Hua Wang
  • About author:
    Corresponding author: Wang Hua, Email:
  • Supported by:
    National Program on Key Basic Reserch Project of China (973 Program)(2013CB967404); Sichuan Science and Technology Program(2014SZ0149, 2016TD0002); Science and Technology Program for Wellbeing of Chengdu Science and Technology Bureau(2015-HM01-00447-SF)
引用本文:

张婷, 王华, 唐军, 母得志. 范可尼贫血诊治分析并文献复习[J]. 中华妇幼临床医学杂志(电子版), 2019, 15(04): 403-409.

Ting Zhang, Hua Wang, Jun Tang, Dezhi Mu. Diagnosis and treatment of Fanconi anemia and literature review[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2019, 15(04): 403-409.

目的

探讨范可尼贫血(FA)患儿的诊治经过、临床特征及预后,并进行相关文献复习。

方法

选择2018年2月13日,四川大学华西第二医院收治的1例FA患儿为研究对象,日龄为生后11 d。采用回顾性分析方法,收集本例患儿的临床病例资料,并对其临床表现和诊治过程进行分析。此外,以"范可尼贫血""免疫紊乱""嵌合体""基因治疗""Fanconi anemia""immune disorder""mosaicism""gene therapy"为关键词,检索中国生物医学文献数据库、中国知网、维普、万方数据库、PubMed和Ovid Medline数据库,文献检索时间设定为上述数据库建库至2019年2月,总结与本例FA患儿相关的发病机制、免疫紊乱、反向嵌合体等,旨在对FA进行分析总结。本研究符合2013年修订的《世界医学协会赫尔辛基宣言》要求。

结果

①对本例FA患儿的研究结果如下。患儿,女性,生后11 d。最初明显表现为血小板计数降低,由166×109/L(2018年2月3日)降至6×109/L(2018年2月6日),继而出现血红蛋白(Hb)值降低,反复治疗效果不佳,停止一切治疗手段姑息观察后,症状却逐渐缓解直至正常,后经基因检查诊断为FA。②FA相关文献检索结果显示,共计检索到4篇FA相关英文文献,涉及8例FA患儿,所有患儿均为体细胞嵌合体,结合本例患儿诊治经验总结和文献分析,对FA发病机制、免疫紊乱和反向嵌合体等方面进行文献复习:FA发病与DNA修复障碍及选择性自噬功能受损有关,而因基因修复障碍导致的染色体不稳定,是FA患儿免疫紊乱异质性和可能自愈的原因。

结论

FA患儿可伴发免疫紊乱,患儿的染色体不稳定性虽可增加肿瘤发生风险,但是也增加了发生反向嵌合体的机会,给FA患儿提供自愈可能性。

Objective

To study the relationship between Fanconi anemia (FA), immune disorder, and the chance of FA child′s self-healing.

Methods

One FA child admitted to West China Second University Hospital, Sichuan University on February 13, 2018 was selected as research subject, and the age was 11 d after birth. The retrospective analysis method was used to collect the clinical data of this child and analyze clinical manifestations, diagnosis and treatment process. In addition, from the establishment of database (Sinomed, CNKI, VIP, Wanfang, PubMed and Ovid Medline) to February 2019, literatures were retrieved with key words including " Fanconi anemia" " immune disorder" " mosaicism" " gene therapy" to find the reported cases of patients with FA similar to this case. The pathogenesis, immune disorder and reverse mosaicism of FA were analyzed and summarized. This study was in line with the World Medical Association Declaration of Helsinki revised in 2013.

Results

①The results of this FA child were as follows. The initial obvious manifestations of this child were a decrease in platelet count from 166×109/L (February 3, 2018) to 6×109/L (February 6, 2018), followed by a decrease in hemoglobin (Hb) level, with poor effect of repeated treatment. After stopping all treatment methods for palliative observation, the symptoms gradually eased until normal. After genetic examination, the patient was diagnosed as FA. ②The search results of FA-related literatures showed that a total of 4 FA-related English literatures were searched, involving 8 cases of FA children, all of whom were somatic chimeras. Based on the diagnosis and treatment experience of the children and literature analysis, literature review was conducted on FA pathogenesis, immune disorder and reverse chimeras. FA pathogenesis was related to DNA repair disorder and selective autophagy dysfunction, while chromosome instability caused by gene repair disorder was the cause of heterogeneity and possible self-healing of FA children.

Conclusions

Children with FA can be accompanied by immune disorder. Although chromosome instability of children can increase the risk of tumor, it also increases the chance of reverse chimerism and provides self-healing possibility for children with FA.

图1 1例范可尼贫血女性患儿(生后47 d) FANCG基因外显子12一代测序结果(患儿FANCG基因exon12:c.1587G>C位点为G/C杂合型,父亲为未突变,母亲为G/C杂合型)
图2 1例范可尼贫血女性患儿(生后47 d) FANCF基因外显子1一代测序结果(患儿exon1:c.772G>A位点为G/A杂合型,父亲为G/A杂合型,母亲为未突变)
图3 1例范可尼贫血女性患儿(生后47 d) FANCA基因外显子21一代测序结果(患儿为A/T杂合型,父亲为未突变,母亲为A/T杂合型)
图4 1例范可尼贫血女性患儿(生后47 d) FANCA基因外显子7一代测序结果(患儿为A/G杂合型,父亲为未突变,母亲为A/G杂合型)
图5 1例范可尼贫血女性患儿(生后47 d) BRIP1基因外显子10一代测序结果(患儿为A/G杂合型,父亲为A/G杂合型,母亲为未突变)
图6 1例范可尼贫血女性患儿生后7个月时门诊随访照片图(患儿生长发育良好)
表1 FA相关文献复习检索的4篇文献报道的8例FA患儿的临床资料
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