To investigate the clinical features and genetic characteristics of patients with late-onset Pompe disease(LOPD).

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.

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 0.3 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*).

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.