{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:30:03Z","timestamp":1791462603422,"version":"4.3.4"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T00:00:00Z","timestamp":1571875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Pompe disease is caused by pathogenic mutations in the alpha 1,4\u2010glucosidase (\n                      <jats:italic>GAA<\/jats:italic>\n                      ) gene and in patients with late onset Pome disease (LOPD), genotype\u2013phenotype correlations are unpredictable. Skeletal muscle pathology includes glycogen accumulation and altered autophagy of various degrees. A correlation of the muscle morphology with clinical features and the genetic background in\n                      <jats:italic>GAA<\/jats:italic>\n                      may contribute to the understanding of the phenotypic variability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Muscle biopsies taken before enzyme replacement therapy were analysed from 53 patients with LOPD. On resin sections, glycogen accumulation, fibrosis, autophagic vacuoles and the degree of muscle damage (morphology\u2010score) were analysed and the results were compared with clinical findings. Additional autophagy markers microtubule\u2010associated protein 1A\/1B\u2010light chain 3, p62 and Bcl2\u2010associated athanogene 3 were analysed on cryosections from 22 LOPD biopsies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The myopathology showed a high variability with, in most patients, a moderate glycogen accumulation and a low morphology\u2010score. High morphology\u2010scores were associated with increased fibrosis and autophagy highlighting the role of autophagy in severe stages of skeletal muscle damage. The morphology\u2010score did not correlate with the patient's age at biopsy, disease duration, nor with the residual GAA enzyme activity or creatine\u2010kinase levels. In 37 patients with LOPD, genetic analysis identified the most frequent mutation, c.\u201032\u201013T&gt;G, in 95%, most commonly in combination with c.525delT (19%). No significant correlation was found between the different\n                      <jats:italic>GAA<\/jats:italic>\n                      genotypes and muscle morphology type.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Muscle morphology in LOPD patients shows a high variability with, in most cases, moderate pathology. Increased pathology is associated with more fibrosis and autophagy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12580","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T08:54:51Z","timestamp":1569228891000},"page":"359-374","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["An integrative correlation of myopathology, phenotype and genotype in late onset Pompe disease"],"prefix":"10.1111","volume":"46","author":[{"given":"M.","family":"Kulessa","sequence":"first","affiliation":[{"name":"Institute of Neuropathology Justus Liebig University Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Weyer\u2010Menkhoff","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology Goethe University Frankfurt\/Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Viergutz","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology Justus Liebig University Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Kornblum","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Bonn Bonn Germany"},{"name":"Center for Rare Diseases University Hospital Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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