脑腱黄瘤病18例临床及分子遗传学特点分析  

Clinical and molecular genetic analysis of 18 cases of cerebrotendinous xanthomatosis

作　　者：田聪 初志飞 张同霞[1] 赵冰 赵秀鹤[1] 赵翠萍 焉传祝[1] 赵玉英[1] Tian Cong;Chu Zhifei;Zhang Tongxia;Zhao Bing;Zhao Xiuhe;Zhao Cuiping;Yan Chuanzhu;Zhao Yuying(Department of Neurology,Qilu Hospital of Shandong University,Jinan 250012,China;Department of Neurology,Boxing People's Hospital,Binzhou 256500,China;Department of Neurology,Qilu Hospital of Shandong University(Qingdao),Qingdao 266035,China)

机构地区：[1]山东大学齐鲁医院神经内科,济南250012 [2]博兴县人民医院神经内科,滨州256500 [3]山东大学齐鲁医院(青岛)神经内科,青岛266035

出　　处：《中华神经科杂志》2024年第11期1217-1226,共10页Chinese Journal of Neurology

摘　　要：目的分析脑腱黄瘤病(CTX)患者的临床及分子遗传学特征,提高临床医生对该病的认识。方法回顾性分析2017年3月至2023年12月在山东大学齐鲁医院神经内科确诊的CTX患者的发病及确诊年龄、临床表现、神经影像学、神经电生理等临床及分子遗传学资料。结果最终共纳入18例CTX患者,其中男性12例,女性6例。起病年龄为10(6,29)岁,最小3岁,最大32岁;起病至确诊时间为19.00(8.75,24.25)年,最短为6个月,最长为35年。18例患者中有16例伴有痉挛性瘫痪的症状及体征,9例患者出现认知障碍和周围神经病,8例患者有小脑性共济失调,3例患者出现精神行为异常,3例有自主神经功能障碍,仅有2例患者有癫痫发作。在非神经系统症状中,9例患者有跟腱黄瘤,其中1例伴有髌腱黄瘤;8例患有青少年白内障,6例患者自幼出现慢性腹泻。对所有患者均行头颅MRI检查,其中15例患者存在小脑齿状核受累,10例存在皮质脊髓束受累,头颅MRI阴性者2例。对14例患者行神经传导及针极肌电图检查,其中9例表现为运动或运动感觉脱髓鞘为主的多发性周围神经病。18例患者共检出17种CYP27A1基因变异,以c.1420C>T和c.1263+1G>A最为常见。结论痉挛性瘫痪、小脑性共济失调、腱黄瘤及青少年白内障是CTX的典型临床表现,神经影像学改变以小脑齿状核和皮质脊髓束受累为主,部分患者缺乏上述典型特征。c.1420C>T和c.1263+1G>A是本队列的热点突变。ObjectiveTo analyze the clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis(CTX)to increase the awareness of the disease among clinicians.MethodsThe clinical data,including the age of onset and diagnosis,clinical manifestations,neuroimaging and neuroelectrophysiology and the genetic data of patients diagnosed with CTX in the Department of Neurology,Qilu Hospital of Shandong University from March 2017 to December 2023 were retrospectively collected and analyzed.ResultsA total of 18 patients were enrolled in this study,including 12 males and 6 females.The onset age was 10(6,29)years,with a minimum onset age of 3 years and a maximum onset age of 32 years;the period from onset to diagnosis was 19.00(8.75,24.25)years,with the shortest being 6 months and the longest being 35 years.Among the 18 patients,16 patients had symptoms and signs of spastic paralysis,9 patients had cognitive impairment and peripheral neuropathy,8 patients had cerebellar ataxia,3 patients had mental disorders,3 patients had autonomic nervous dysfunction,and only 2 patients had seizures.Among the non-neurological symptoms,9 patients had Achilles tendon xanthoma,of whom 1 patient was accompanied by patellar tendon xanthoma;8 patients had adolescent cataracts,6 patients had chronic diarrhea since childhood.All patients underwent brain MRI examination,among whom 15 patients had cerebellar dentate nucleus involvement,10 patients had corticospinal tract involvement and 2 patients had normal brain MRI.Fourteen patients underwent nerve conduction and electromyography examinations,among whom 9 patients presented with multiple peripheral neuropathy characterized by motor or motor sensory demyelination.A total of 17 CYP27A1 gene variants were detected in 18 patients.The c.1420C>T and c.1263+1G>A were the hot-spot mutations in this cohort.ConclusionsSpastic paralysis,cerebellar ataxia,tendon xanthoma and adolescent cataracts are typical manifestations of CTX.The cerebellar dentate nucleus and corticospinal tract are

关 键 词：黄瘤病 脑腱性 临床表现 CYP27A1基因 代谢疾病 胆固醇代谢 

分 类 号：R742[医药卫生—神经病学与精神病学]