Identification of miRNAs Associated with Infantile-Onset Pompe Disease

Introduction: Infantile-onset Pompe disease, which presents with a broad spectrum of nonspecific findings in newborns and lacks a clearly defined clinical picture, is a significant factor that delays patients’ access to diagnosis and treatment. In this disease, insufficient diagnosis rates, low levels of clinical suspicion, and delays in diagnosis are the main problems that hinder early and accurate diagnosis. This study aims to address diagnostic and therapeutic challenges by elucidating the functional roles and associations of microRNAs in the pathogenesis of infantile-onset Pompe disease. As a result of comparative data analysis, an inventory of known and novel microRNA sequences predicted to target pathogenic pathways associated with infantile-onset Pompe disease was established. Methods: In this study, IOPD and control samples from GSE38680 data were normalized on the Affymetrix platform. Differential gene expression analysis was performed using the limma package, and common DEGs were identified. Subsequently, significant signaling pathways were identified using WebGestalt and Reactome/KEGG/GO databases, and FDR correction was applied. Finally, miRNA expression analysis and miRNA interactions associated with IOPD genes were examined using R packages such as DESeq2, miRNATap, and multiMiR. Results: In this study, 1967 differentially expressed genes (1108 upregulated, 859 downregulated) were identified in the GSE38680 data. GO and KEGG analyses revealed biological processes associated with IOPD, particularly muscle function and the lysosome pathway. The miRNA analysis identified 54 candidate miRNAs, of which only hsa-miR-4749-3p was found to bind directly to the 3′-UTR region of the GAA gene. Conclusion: Early diagnosis is critical to prevent or mitigate irreversible organ damage associated with the progression of IOPD, and circulating miRNAs may serve as additional biomarkers for diagnosis, disease severity, and treatment response. This study used high-throughput technology to identify potential miRNAs for IOPD.