上海交通大学学报（医学版）

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2022 , Vol. 42 >Issue 7: 964 - 970

DOI: https://doi.org/10.3969/j.issn.1674-8115.2022.07.018

病例报告

EIF2B基因新突变致白质消融性白质脑病2例及文献复习

  • 刘桃桃 ,
  • 邬静莹 ,
  • 刘晓黎 ,
  • 张梅 ,
  • 曹立
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  • 1.上海交通大学医学院附属第六人民医院神经内科，上海 200233
    2.安徽理工大学第一附属医院神经内科，淮南 232007
    3.上海市奉贤区中心医院神经内科，上海 201400
刘桃桃（1991—），女，硕士生；电子信箱：liutt@rjlab.cn。
曹立，电子信箱：caoli2000@yeah.net。

收稿日期: 2022-02-28

  录用日期: 2022-06-08

  网络出版日期: 2022-07-25

基金资助

国家自然科学基金(81870889)

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Two cases of leukoencephalopathy with vanishing white matter caused by new mutation of EIF2B gene and literature review

  • Taotao LIU ,
  • Jingying WU ,
  • Xiaoli LIU ,
  • Mei ZHANG ,
  • Li CAO
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  • 1.Department of Neurology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
    2.Department of Neurology, The First Affiliated Hospital of Anhui University of Science and Technology, Huainan 232007, China
    3.Department of Neurology, Shanghai Fengxian District Central Hospital, Shanghai 201400, China
CAO Li, E-mail: caoli2000@yeah.net.

Received date: 2022-02-28

  Accepted date: 2022-06-08

  Online published: 2022-07-25

Supported by

National Natural Science Foundation of China(81870889)

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摘要

该文报道2例白质消融性白质脑病（leukoencephalopathy with vanishing white matter，VWM）。患者1，女，2岁3个月，临床以反复感染后运动能力倒退为主要表现，病情进展迅速，发病6个月时有癫痫发作，此后患者不能独立行走，吞咽困难；基因检测发现，该患者的EIF2B4基因存在7号外显子c.594C>G（p.I98M）和11号外显子c.1177T>A（p.Y393N）的复合杂合突变，其中前者来自父亲、后者来自母亲，且2个位点均是未曾报道的新错义突变。患者2，女，41岁，临床以进行性双下肢无力及记忆力减退为主要表现；基因检测发现，该患者的EIF2B3基因存在2号外显子c.130G>A（p.G44K）和8号外显子c.934C>G（p.R312G）的复合杂合突变，其中后者位点的突变已有报道，但此突变类型为首次报告，且该患者是中国报道的第2例成人型VWM。2例患者的头颅磁共振成像均表现为弥漫对称性脑白质病变；其中，患者1白质稀薄更突出，患者2主要表现为白质萎缩、脑室扩大。发病年龄是VWM严重程度的临床预测因子，起病越早则病情进展越迅速。应激是发病及神经恶化的诱因，目前VWM尚无有效的治疗方法。该文对上述2个病例进行报道，旨在提升临床医师对疾病的认识及早期诊断的能力，以期延缓疾病的进展、延长患者的生存期。

关键词： 白质消融性白质脑病; EIF2B基因; 癫痫; 感染

本文引用格式

刘桃桃 , 邬静莹 , 刘晓黎 , 张梅 , 曹立 . EIF2B基因新突变致白质消融性白质脑病2例及文献复习[J]. 上海交通大学学报（医学版）, 2022 , 42(7) : 964 -970 . DOI: 10.3969/j.issn.1674-8115.2022.07.018

Abstract

Two cases of leukoencephalopathy with vanishing white matter (VWM) were reported. Patient 1 was a two years and three months old girl whose main clinical manifestation was rapidly progressive motor disturbance following recurrent infections. She developed epilepsy after 6 months. After that, she was unable to walk independently and had difficulty in swallowing. Genetic testing revealed that there were compound heterozygous mutations in the EIF2B4 gene of the proband, including the c.594C>G (p.I98M) in exon 7 inherited from father and the c.1177T>A (p.Y393N) in exon 11 inherited from mother that both had not been reported previously. Cranial MRI showed diffuse symmetrical white matter lesions with prominent white matter thinning. Patient 2 was a 41-year-old female, the second adult VWM case reported in China, mainly manifesting as progressive weakness in both lower limbs and memory loss. Genetic testing revealed that there were compound heterozygous mutations in the EIF2B3 gene of the proband, including the c.130G>A (p.G44K) in exon 2 and the c.934C>G (p.R312G) in exon 8, in which the latter mutation type was reported for the first time. Cranial MRI showed white matter atrophy and ventriculomegaly. Age was a clinical predictor of the severity of VWM, and specifically earlier onset could be associated with more severe disability and higher mortality. Stress was a trigger for the disease and could contribute to neurological deterioration. At present, there is no effective therapy method for this disease. This article reports the two cases, aiming to improve clinicians' understanding of the disease and their ability of early diagnosis, so as to delay the progress of the disease and prolong the survival of the patients.

Key words： leukoencephalopathy with vanishing white matter (VWM); EIF2B gene; epilepsy; infection

参考文献

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