13例晚发型庞贝病临床特征分析  

Analysis of Clinical Features of 13 Cases with Late-Onset Pompe Disease

作　　者：纪芳[1] 何芳萍[1] 李亦 倪婕 余丽华 孟繁霞[1] 陈海岩 柯青[1,2,3] JI Fang;HE Fangping;LI Yi;NI Jie;YU Lihua;MENG Fanxia;CHEN Haiyan;KE Qing(Department of Neurology,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;Department of Neurology,the First Affiliated Hospital,Zhejiang University School of Medicine,Jiangxi Hospital,Nanchang 330006,China;Department of Neurology,the Second Affiliated Hospital of Nanchang University,Nanchang 330006,China)

机构地区：[1]浙江大学医学院附属第一医院神经内科,杭州310003 [2]浙江大学医学院附属第一医院江西医院神经内科,南昌330006 [3]南昌大学第二附属医院神经内科,南昌330006

出　　处：《罕见病研究》2024年第3期318-325,共8页Journal of Rare Diseases

基　　金：浙江省科技计划项目(2023C03003);江西省创新领军人才(jxsq2023102164)。

摘　　要：目的探讨晚发型庞贝病(LOPD)患者的临床特征和基因突变特点。方法选取2020年9月至2023年12月在浙江大学医学院附属第一医院确诊为LOPD的13例患者,对所有患者进行临床调查、GAA活性检测和GAA基因检测。结果13例患者中男7例,女6例;家系患者5例,散发患者8例;中位发病年龄17岁(8~52岁),中位就诊年龄24岁(10~52岁),中位确诊年龄31岁(14~58岁)。患者首发症状,10例患者表现为肢体无力,3例患者表现为呼吸困难。血清肌酸激酶平均水平552 U/L(55~1084 U/L),1例患者血清肌酸激酶水平正常。13例患者均有脊柱侧弯、不同程度限制性通气功能障碍。9例患者行神经电生理检查均提示肌源性损害,其中8例患者有临床下肌强直放电。GAA活性平均值0.3μmol/(L·h)[0.17~0.5μmol/(L·h)]。共检出GAA基因13个变异位点,最常见突变位点c.2238G>C(p.W746C)。发现c.543del(p.F181Lfs*40)、c.839_840insCC(p.R281Pfs*34)、c.1800_1823del(p.S601_R608del)、c.2296T>C(p.Y766H)、c.995C>A(p.S332*)共5个新变异位点。结论LOPD是一种容易延误诊断的罕见病。肢体近端无力、呼吸功能下降、肌酸激酶轻中度升高、脊柱侧弯、肌电图提示临床下肌强直放电是LOPD的高危“画像”。c.2238G>C(p.W746C)是其热点突变,新发现的5个GAA变异位点丰富了GAA基因突变谱系。Objective To investigate the clinical features and genetic characteristics of patients with late-onset Pompe disease(LOPD).Methods A total of 13 patients diagnosed with LOPD in the First Affiliated Hospital of Zhejiang University School of Medicine from September 2020 to December 2023 were selected,and all patients were subjected to clinical investigation,GAA activity detection and GAA gene testing.Results Among the 13 patients,7 were males and 6 were females;5 were family patients and 8 were sporadic patients;and the median age of onset was 17 years(8-52 years),the median age of presentation was 24 years(10-52 years),and the median age of diagnosis was 31 years(14-58 years).In terms of the first symptoms,10 patients presented with limb weakness and 3 patients presented with dyspnea.The average serum creatine kinase level was 552 U/L(55-1084 U/L),and the serum creatine kinase level was normal in one patient.All patients had scoliosis and different degrees of restrictive ventilatory dysfunction.Neuroelectrophysiological examinations of 9 patients showed myogenic damage,and 8 of them had muscle tonic discharge.The mean value of GAA activity was 0.3μmol/(L·h)[0.17-0.5μmol/(L·h)].A total of 13 mutations were detected in GAA gene,and the most common mutation was c.2238G>C(p.W746C).There were five new variant sites:c.543del(p.F181Lfs*40),c.839_840insCC(p.R281Pfs*34),c.1800_1823del(p.S601_R608del),c.2296T>C(p.Y766H)and c.995C>A(p.S332*).Conclusions LOPD is a rare disease that tends to delay diagnosis.Proximal limb weakness,decreased respiratory function,mild-to-moderate elevation of creatine kinase,scoliosis,and clinical inferior tonic discharge on electromyography are high-risk images of LOPD.c.2238G>C(p.W746C)is a hotspot mutation,and the discovery of five new mutations enriches the GAA gene mutations lineage.

关 键 词：晚发型庞贝病 酸性α-葡萄糖苷酶 酸性α-葡萄糖苷酶基因 突变 临床特征 

分 类 号：R74[医药卫生—神经病学与精神病学]