中国成年脑腱黄瘤病临床和基因特征及一家系分析  

Clinical and genetics characteristics of adult-onset cerebrotendinous xanthomatosis:analysis of a Chinese pedigree

作　　者：赵博 王志伟 张亦默 俞英欣 姚生 赵津京 李航 梁骊 潘树义 钱海蓉 Zhao Bo;Wang Zhiwei;Zhang Yimo;Yu Yingxin;Yao Sheng;Zhao Jinjing;Li Hang;Liang Li;Pan Shuyi;Qian Hairong(Department of Hyperbaric Oxygen,Sixth Medical Center of Chinese PLA General Hospital,Beijing 100048,China;the Second School of Clinical Medicine,Southern Medical University,Guangzhou 510515,China;Senior Department of Neurology,Chinese PLA General Hospital,Beijing 100853,China;Department of Neurology,the 305th Hospital of the People′s Liberation Army,Beijing 100017,China;Navy Clinical College,the Fifth School of Medicine,Anhui Medical University,Hefei 230032,China)

机构地区：[1]解放军总医院第六医学中心高压氧科,北京100048 [2]南方医科大学第二临床医学院,广州510515 [3]解放军总医院神经内科医学部,北京100853 [4]解放军第三○五医院神经内科,北京100017 [5]安徽医科大学第五临床医学院海军临床学院,合肥230032

出　　处：《中华内科杂志》2023年第4期401-409,共9页Chinese Journal of Internal Medicine

基　　金：首都卫生发展科研专项(2020-2-5115)。

摘　　要：目的:分析并总结中国成年脑腱黄瘤病(CTX)患者的临床表现、影像学改变、病理特点以及基因变异等方面特征,提高临床医生对于CTX的认识,以利于早发现、早诊断、早治疗。方法:收集解放军总医院第六医学中心2020年8月就诊的1例CTX患者家系病史、神经系统查体、辅助检查、影像学及基因检查结果等临床资料,系统检索国内外主要数据库报道的经基因诊断的中国成年CTX病例,回顾性分析发病年龄、首发症状、常见症状体征、病理结果、头颅磁共振成像(MRI)影像学改变及基因突变特征。结果:患者女性,39岁,神经系统及其他系统广泛受累且发病较早,神经系统主要表现为认知功能障碍及共济失调,其他系统受累主要表现为幼年白内障、肌腱肿物。头颅MRI以脑萎缩、对称性锥体束为主的白质病变和小脑齿状核对称性病变为特征性表现。患者固醇-27-羟化酶(CYP27A1)基因存在c.1477-2A>C纯合突变,为全球首例。鹅脱氧胆酸治疗效果较好。该家系中无类似临床表现患者,但发现了c.1477-2A>C突变基因携带者。结合文献,发现中国成年CTX患者多报道于华东地区55.4%(31/56),男女性别比为1.8∶1,发病年龄为9(6,17)岁,病程23(10,29)年,确诊年龄20~49(35±7)岁,可以累及神经系统、肌腱、晶状体、肺、骨骼肌等多个器官组织,神经系统受累最为明显,以认知功能障碍84.6%(44/52)、共济失调86.3%(44/51)为其常见表现。本病具有起病早,多系统慢性进行性损害,病程长,诊断晚,预后差等特点。经基因诊断的中国成年CTX患者最常见的两种基因突变是c.1263+1G>A和c.379C>T,CYP27A1基因2号外显子是突变的热点区域。结论:中国成年CTX患者临床特征复杂,诊断周期长,基因突变位点较多,早期诊治可改善预后,需引起关注。Objective Clinical manifestations,imaging findings,pathologic features,and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis(CTX)were analyzed in order to achieve a greater understanding of CTX that can improve early detection,diagnosis,and treatment.Methods Clinical data including medical history,neurologic and auxiliary examinations,imaging findings,and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People′s Liberation Army General Hospital in August 2020.Additionally,a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset,first symptoms,common signs and symptoms,pathologic findings,imaging changes,and gene mutations were analyzed.Results The proband was a 39-year-old female with extensive,early-onset nervous system manifestations including cognitive dysfunction and ataxia.Systemic lesions included juvenile cataract and a tendon mass.Cranial magnetic resonance imaging revealed cerebral atrophy,symmetric white matter changes predominantly in the pyramidal tract,and lesions in the cerebellar dentate nucleus.A novel homozygous mutation in the sterol-27-hydroxylase(CYP27A1)gene(c.1477-2A>C)was identified.There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation.The patient showed a good response to deoxycholic acid treatment.Totally there were 56 cases of adult CTX patients in China,mostly in East China(31/56,55.4%),at a male-to-female ratio of 1.8 to 1.Multiple organs and tissues including nervous system,tendon,lens,lung,and skeletal muscle were affected in these cases.The most common neurologic manifestations were cognitive dysfunction(44/52,84.6%)and ataxia(44/51,86.3%).The cases were characterized by early onset,chronic progressive damage of multiple systems,long disease course,and delayed diagnosis,making the disease difficult to manage clinically and result

关 键 词：黄瘤病 脑腱性 CYP27A1基因 共济失调 认知障碍 鹅脱氧胆酸 

分 类 号：R742[医药卫生—神经病学与精神病学]