Pathophysiological mechanisms of organ injury in Fabry disease: Update via multi-omics

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in GLA gene, which result in deficient α-galactosidase A activity, leading to intralysosomal accumulation of metabolic substrates and multi-organ injury. Due to the heterogeneity of clinical phenotypes and limitations of current diagnostic modalities, the diagnosis of FD remains challenging. Enzyme replacement therapy is the cornerstone of FD treatment. However, this therapy cannot fully reverse pre-existing organ damage, and patients will still face an unfavorable prognosis. The mechanisms of organ injury in FD cannot fully explain reduced enzyme activity alone and therefore warrant further elucidation. In recent years, omics, including transcriptomics, proteomics, and metabolomics, have demonstrated great potential for elucidating FD pathophysiology, identifying novel biomarkers, and uncovering therapeutic targets. This review presents the pathophysiological mechanisms of FD in its principal target organs and summarizes recent advances in omics applied to its primary target organs, chiefly the kidney and heart. Omics-based investigations hold promise for advancing precision medicine in FD, offering new avenues for early diagnosis and personalized therapy.