Metabolic and proteomic profiles provide insights on mechanism of late onset Pompe disease.

Late onset Pompe disease (LOPD) is caused by a deficiency of the enzyme acid α-glucosidase, resulting in glycogen accumulation in lysosomes. The mechanism of LOPD has been less explored. In this study, we used an integrative analysis of the proteomics and metabolomics of LOPD muscle samples to reveal the potential mechanisms. Proteomic analysis identified 635 upregulated proteins and 89 downregulated proteins in the LOPD group. Similarly, metabolomic analysis revealed 15 upregulated and 143 downregulated metabolites; notably, L-arginine levels were significantly decreased in the LOPD group. Lysosome-related GO terms were significantly upregulated, while GO terms related to neurofilament, cytoskeleton, axon ensheathment, and myelin sheath were significantly downregulated. KEGG pathway analysis demonstrated that the lysosome, autophagy, and mTOR pathways were distinctly upregulated. Correlation analysis indicated that CALML3 showed a potential correlation with LOPD severity. Our study highlighted the potential crosstalk among these LOPD-related pathways. Supplementation with L-arginine could represent a promising therapeutic approach for LOPD, and CALML3 could serve as a potential biomarker for LOPD severity. These findings provide valuable insights into the pathogenesis of LOPD and suggest avenues for future therapeutic development.