摘要
目的探讨RANBP2基因突变致家族性急性坏死性脑病(ANE1)的临床特征、诊治及预后。方法选择2018年1月及2019年3月,于北京儿童医院(患儿1)及四川省妇幼保健院(患儿2)确诊的2例RANBP2基因突变所致ANE1患儿为研究对象。回顾性分析其临床病例资料,包括临床表现、实验室检查结果、头颅MRI特征、治疗及随访结果等。同时,检索国内外数据库中RANBP2基因突变所致ANE1患者相关文献进行复习。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。结果①临床病例资料:患儿1系发热后头痛、嗜睡、精神反应差、表情淡漠、直线行走不稳、近期记忆力下降;患儿2系甲型流感病毒感染后,出现发热、头痛、呕吐、进行性意识障碍伴面瘫。2例患儿头颅MRI检查均提示丘脑、岛叶、脑桥、外囊等多部位对称性损害,部分囊性改变。基因检测结果显示,2例患儿均为RANBP2基因第12外显子c.1754 C>T(p.Thr585Met)杂合错义突变;经丙种球蛋白、糖皮质激素调节免疫功能治疗,以及“线粒体鸡尾酒疗法”修复线粒体功能等治疗后,患儿颅内病灶均好转,精神及运动能力均恢复。②文献复习:总结文献报道的74例及本组2例RANBP2基因突变所致ANE1患者临床特征如下。其发病年龄为5个月至40岁,首发年龄中位数为3.5岁,男女患者比例为35∶41。其主要临床表现中,发热为82.5%(47/57),癫痫发作为81.1%(43/53),局灶性神经功能障碍(FND)为28.6%(8/28),脑病为93.4%(71/76);脑脊液蛋白升高(EP)为90.3%(56/62),脑脊液细胞数增多(Pl)为28.6%(8/28)。患儿头颅MRI/CT检查提示的病变部位,主要位于丘脑(83.1%,49/59),脑干(72.9%,43/59),颞叶(71.2%,42/59),小脑(26.3%,5/19),脊髓(13.8%,4/29),基底节(8.5%,5/59)。结论RANBP2基因突变所致ANE1,具有典型临床症状和特征性头颅MRI表现,临床对发热性疾病伴丘脑等部位对称性损害患者,应注意本病可能。对疑似该病的患者,应尽早进行RANBP2基因检测,将有助于明确本病诊断、进行合理治疗并改善患者预后。
Objective To investigate clinical characteristics,diagnosis,treatment and prognosis of familial acute necrotizing encephalopathy(ANE1)caused by RANBP2 gene mutation.Methods A total of 2 children with ANE1 caused by RANBP2 gene mutation who were confirmed in Beijing Children′s Hospital in January 2018(case 1)and in Sichuan Provincial Hospital for Women and Children in March 2019(case 2),were chosen as research subjects.We retrospectively analyzed their clinical case data,including clinical manifestations,laboratory examination results,head MRI features,treatment and follow-up data.Meanwhile,literature related to ANE1 caused by RANBP2 gene mutation were searched in mainstream databases for literature review.And the procedure followed in the whole study were in accordance with World Medical Association Declaration of Helsinki revised in 2013.Results①Clinical case data:clinical manifestation of case 1 was presented with headache after fever,drowsiness,poor mental response,indifferent expression,unstable walking in a straight line,and recent memory decline;and of case 2 with fever,headache,vomiting,progressive disturbance of consciousness and facial paralysis after infection of influenza A virus.Their head MRI examinations revealed symmetrical damage to multiple parts of thalamus,insula,pons and external capsule,with some cystic changes.Their gene detection results showed that heterozygosity mutation of RANBP2 gene on exon 12:c.1754 C>T(p.Thr585Met),a missense mutation.After treatment with gamma globulin,glucocorticoids to regulate immunity,and"mitochondrial cocktail therapy"to repair mitochondrial function,their intracranial lesions improved,and mental and athletic abilities were restored.②Clinical features of ANE1 caused by RANBP2 gene mutation of 74 cases by literature review and 2 cases in this study were summarized.Their clinical features were as follows:their age of onset ranged from 5 months to 40 years old,median age of first onset was 3.5 years old,the ratio of male to female patients was 35∶41.Among main clinical manifestations,ratio of fever was 82.5%(47/57),epilepsy was 81.1%(41/53),focal neurological deficit(FND)was 28.6%(8/28),encephalopathy was 93.4%(71/76),elevated CSF protein(EP)was 90.3%(56/62),pleocytosis in CSF(Pl)was 28.6%(8/28).Head MRI/CT showed that main lesions of patients were located in thalami(83.1%,49/59),brainstem(72.9%,43/59),temporal lobe(71.2%,42/59),cerebellum(26.3%,5/19),spinal cord(13.8%,4/29),basal ganglia(8.5%,5/59).Conclusions ANE1 caused by RANBP2 gene mutation has typical clinical features and characteristic head MRI findings.Febrile disease with symmetrical lesions in thalamus and other brain parts should be a vigilant signal to ANE1 patients.For patients suspected of ANE1,early detection of RANBP2 gene will be helpful to clarify diagnosis,rational treatment and improve their prognosis.
作者
罗泽民
李久伟
刘星宇
蒋琼
朱书瑶
谢丹凤
Luo Zemin;Li Jiuwei;Liu Xingyu;Jiang Qiong;Zhu Shuyao;Xie Danfeng(Department of Pediatric Neurology,Sichuan Provincial Hospital for Women and Children,Chengdu 610045,Sichuan Province,China;Department of Neurology,Beijing Children′s Hospital Affiliated to Capital Medical University,Beijing 100045,China)
出处
《中华妇幼临床医学杂志（电子版）》
CAS
2020年第4期398-408,共11页
Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)
基金
四川省卫健委科研课题(19PJ256)。
关键词
急性发热性脑病
家族性
Ran结合蛋白2
磁共振成像
遗传学
突变
误义
丘脑
儿童
Acute febrile encephalopathy
Familial
Ran-binding protein 2
Magnetic resonance imaging
Genetics
Mutation,missense
Thalamus
Child
