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 Affilia-ted 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 pa-tients 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 pa-tients had scoliosis and different degrees of restrictive ventilatory dysfunction.Neuroelectrophysiological exami-nations of 9 patients showed myogenic damage,and 8 of them had muscle tonic discharge.The mean value of GAA activity was 0.3 µmol/(L·h)[0.17-0.5 μmol/(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
Key words
late-onset Pompe disease/acid alpha-glucosidase/acid alpha-glucosidase gene/mutation/clinical features
维普
万方数据