中国成人型Krabbe病的临床表型与分子遗传学特征  

Clinical phenotype and molecular genetic characteristics of adult Krabbe disease in China

作　　者：汪国语 翟建昭 钟慧钰 刘堂瑜亨 焦琳 贺勇[1] 应斌武[1] 王旻晋[1] WANG Guoyu;ZHAI Jianzhao;ZHONG Huiyu;LIU Tangyuheng;JIAO Lin;HE Yong;YING Binwu;WANG Minjin(Department of Clinical Laboratory,West China Hospital,Sichuan University,Chengdu 610041,Sichuan,China)

机构地区：[1]四川大学华西医院实验医学科,四川成都610041

出　　处：《检验医学》2025年第2期121-130,共10页Laboratory Medicine

基　　金：四川省科技计划项目(2024YFFK0144)。

摘　　要：目的对中国成人型Krabbe病(KD)的临床表型和分子遗传学特征进行文献回顾,以提高临床诊断能力。方法选取2020年1月—2024年11月四川大学华西医院成年遗传性脑白质病(GLES)疑似患者89例,对所有患者行全外显子组基因检测,对筛选出的5例成人型KD患者的临床资料进行回顾性分析。检索既往报道的中国成人型KD相关文献,对成人型KD的临床表型和分子遗传学特征进行总结和分析。结果5例KD患者中有1例临床表现为精神障碍、智力下降,以精神障碍为临床首发症状。在5例KD患者中发现2个未被报道的突变c.1164_1165del和c.581G>T,其中c.1164_1165del评级为可能致病,携带c.581G>T突变的患者以精神障碍为首发症状。共检索到15篇文献,涉及27例成人型KD患者。32例成人型KD患者主要临床表现为行走困难和步态障碍(80.0%)、周围神经损伤(60.0%)、痉挛性瘫痪(40.0%);神经系统检查常见下肢肌力降低、肌张力增高、反射亢进和病理征阳性;肌电图主要表现为运动神经和感觉神经传导异常;影像学检查大多表现为T2高信号,常见于脑白质和皮质脊髓束区域。遗传学分析发现29种GALC变异,最常见的变异是c.1901T>C,其次为c.136G>T。结论中国成人型KD以c.1901T>C突变最为常见,临床症状常表现为行走困难和步态障碍、周围神经损伤。不同变异位点和基因型的KD患者临床表现多样,具有脑白质病变影像学改变的癫痫发作、精神障碍、智力下降的病因不明患者应考虑KD,通过基因检测可明确诊断。Objective To review the literatures on the clinical phenotype and molecular genetic characteristics of adult Krabbe disease(KD)in China,so as to improve the ability of clinical diagnosis.Methods From January 2020 to November 2024,89 patients with suspected genetic leukoencephalopathy(GLES)in West China Hospital of Sichuan University were screened for whole-exome sequencing,5 patients with adult KD were enrolled,and their clinical data were analyzed retrospectively.By retrieving literatures,the clinical phenotype and molecular genetic characteristics of adult KD in China were summarized and analyzed.Results One of the 5 cases presented with mental disorder and mental decline.Mental disorder was the first clinical symptom.Two unreported mutations,c.1164_1165del and c.581G>T,were identified in the 5 cases,and c.1164_1165del may be likely pathogenic,while mental disorder was the first clinical symptom in patients with c.581G>T.A total of 15 literatures were searched for 27 adult KD patients.A total of 32 Chinese patients with adult KD were reviewed.The main clinical symptoms were walking difficulty and gait disturbance(80.0%),peripheral nerve damage(60.0%)and spastic paralysis(40.0%).The common findings of nervous system examination were decreased muscle strength,hypertonia,hyperreflexia and positive pathological signs of lower limbs.Electromyography showed abnormal conduction of motor and sensory nerves.Most of the imaging examinations showed T2 hyperintensity,which was common in the white matter and corticospinal tract area.Genetic analysis revealed 29 GALC mutations,the most common one was c.1901T>C,the second one was c.136G>T.Conclusions The c.1901T>C is the most common mutation of adult KD in Chinese.The clinical symptoms are often characterized by walking difficulty and gait disturbance and peripheral nerve damage.The clinical symptoms of KD patients with different mutation sites and genotypes are diverse.KD should be considered in patients with seizure,mental disorder,mental decline and unknown etiology who ha

关 键 词：半乳糖脑苷脂酶 Krabbe病 临床表型 分子遗传学特征 

分 类 号：R446.5[医药卫生—诊断学]