{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:53:41Z","timestamp":1777953221527,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["No. 2021YFC2700904"],"award-info":[{"award-number":["No. 2021YFC2700904"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701238"],"award-info":[{"award-number":["81701238"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471428"],"award-info":[{"award-number":["82471428"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction\/Aims<\/jats:title>\n                    <jats:p>\n                      Although asymptomatic or pre\u2010symptomatic Pompe disease is increasingly recognized, early skeletal muscle pathology and the role of residual glycogen at this stage remain unclear. Here, we investigated early muscle pathological changes using human samples and an early\u2010stage\n                      <jats:italic>Gaa<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mouse model, focusing on residual glycogen accumulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Clinical, genetic, imaging, and muscle pathological analyses were performed in an asymptomatic Pompe disease patient carrying a novel\n                      <jats:italic>GAA<\/jats:italic>\n                      variant. Skeletal muscle samples from asymptomatic and symptomatic patients, as well as from early\u2010stage and late\u2010stage\n                      <jats:italic>Gaa<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, were analyzed using histochemistry, immunohistochemistry, immunofluorescence, and Western blotting to assess residual glycogen accumulation and lysosome\u2010associated pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a novel mutation, c.361C\u2009&gt;\u2009T, in an asymptomatic Pompe disease patient. Despite the lack of symptoms, residual glycogen accumulated in muscle lysosomes. Immunohistochemistry showed positive glycogenin expression, while LAMP1 and LC3 were negative, suggesting early glycogenin detection. Western blot revealed increased glycogenin and STBD1, with mild LAMP1 and LC3 upregulation. In 1\u2010month\u2010old\n                      <jats:italic>Gaa<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, glycogenin, LAMP1, STBD1, and LC3 were all upregulated. Furthermore, immunofluorescence further showed glycogenin\/LAMP1 double\u2010positive muscle fibers in both the patient and mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our study shows that key pathological changes in Pompe disease occur during the asymptomatic stage, with early lysosomal accumulation of residual glycogen. This suggests residual glycogen may serve as a biomarker of early disease activity and a potential target for early intervention, informing disease monitoring and the timing of enzyme replacement therapy (ERT). Further studies are needed to validate its clinical utility and explore strategies for early clearance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mus.70233","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T06:32:42Z","timestamp":1775111562000},"page":"1172-1181","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased Glycogenin\u2010Exposed Residual Glycogen in Lysosomes Is the Early Pathological Finding in Asymptomatic Pompe Disease"],"prefix":"10.1002","volume":"73","author":[{"given":"Yixin","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Diseases, Research Institute of Neuromuscular and Neurodegenerative Diseases Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanhan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Diseases, Research Institute of Neuromuscular and Neurodegenerative Diseases Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Diseases, Research Institute of Neuromuscular and Neurodegenerative Diseases Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Diseases, Research Institute of Neuromuscular and Neurodegenerative Diseases Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanzhu","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Diseases, Research Institute of Neuromuscular and Neurodegenerative Diseases Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Diseases, Research Institute of Neuromuscular and Neurodegenerative Diseases Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duoling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Diseases, Research Institute of Neuromuscular and Neurodegenerative Diseases Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512481"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.04.025"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010018\u20100655\u2010y"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000252798.25690.76"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2019.03.008"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408363.2025.2527288"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R117.802843"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2018.06.014"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.52"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2006.04.001"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.49860"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.6255"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u2010291x(85)91206\u20109"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.9.12.7672505"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111041"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201014993\u2010y"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq270"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010011\u20109388\u20103"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.166.1.at1102"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01753355"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2004.07.036"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010011\u20106193\u20108"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2023.07.008"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1969633"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.05.004"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.86821"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2200587"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016\u20100280E"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1590\/0004\u2010282X20150194"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13285"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2023.10.001"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23878"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.12.014"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2012_138"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.855510"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.03.004"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.24653"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27099"}],"container-title":["Muscle 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