Increased Glycogenin‐Exposed Residual Glycogen in Lysosomes Is the Early Pathological Finding in Asymptomatic Pompe Disease

INTRODUCTION/AIMS: mouse model, focusing on residual glycogen accumulation. METHODS: mice, were analyzed using histochemistry, immunohistochemistry, immunofluorescence, and Western blotting to assess residual glycogen accumulation and lysosome-associated pathways. RESULTS: mice, glycogenin, LAMP1, STBD1, and LC3 were all upregulated. Furthermore, immunofluorescence further showed glycogenin/LAMP1 double-positive muscle fibers in both the patient and mice. DISCUSSION: 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.