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There are two different clinical phenotypes, which are based on the age of onset,\n                    <jats:italic>GAA<\/jats:italic>\n                    variants, and residual enzyme activity. To better understand the regulation of age\u2010dependent pathways in Pompe disease, we performed a multi\u2010modal approach. We included mass spectrometry (MS) (liquid chromatography coupled to tandem mass spectrometry) and bulk\u2010RNA sequencing on skeletal muscle samples from patients with late onset Pompe disease (LOPD) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200921) and infantile\u2010onset Pompe disease (IOPD) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200911) naive to enzyme replacement therapy (ERT), IOPD patients with ERT (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095) and age\u2010matched controls. The findings were verified by immunofluorescence studies and ultrastructural analysis using samples with different disease progression. We identified deregulated muscle processes in LOPD and IOPD samples, with different levels of regulation evident at the transcriptome and protein levels. Transcriptomic profiling revealed upregulation of immune processes in both Pompe subtypes, while metabolic processes were downregulated mainly in LOPD. Downregulation of transcripts associated with muscle development and myogenesis was only observed in IOPD samples. MS analysis revealed a decrease in the expression of sarcomeric proteins mainly in LOPD, while chaperone\u2010assisted selective autophagy was altered in both Pompe subtypes. Proteins linked to vesicle trafficking and biosynthesis correlated with the degree of muscle pathology in LOPD, highlighting their role in the progression of the disease. IOPD patients treated with ERT showed normalised deregulated transcripts, though not fully back to baseline. Proteins increased with ERT were linked with mitochondrial and protein control pathways, and sarcomeric function, indicating ERT's positive effect on skeletal muscle function at the molecular level. Our findings reveal that combining a multi\u2010omic approach, including morphological observations, enables the detection of a greater number of deregulated muscle processes, indicating both similar and distinct muscle processes in IOPD and LOPD.\n                  <\/jats:p>","DOI":"10.1111\/bpa.70155","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:17:39Z","timestamp":1791415059000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identifying regulatory muscle processes in infantile and adult Pompe patients using a multi\u2010omic and morphological approach"],"prefix":"10.1111","author":[{"given":"Alexander","family":"Schaiter","sequence":"first","affiliation":[{"name":"Institute of Neuropathology Justus\u2010Liebig\u2010University Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keerthika","family":"Lohanadan","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Institute for Cell Biology University of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0089-4473","authenticated-orcid":false,"given":"Alexander","family":"Mensch","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medicine Halle  Halle (Saale) Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hentschel","sequence":"additional","affiliation":[{"name":"Leibnitz\u2010Institut f\u00fcr Analytische Wissenschaften\u2014ISAS\u2014e.V.  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