Fabry Disease: Current Perspectives on Diagnosis and Management Strategies

Fabry disease is a rare, X-linked lysosomal storage disorder caused by deficient α-galactosidase A activity, leading to progressive accumulation of globotriaosylceramide in multiple tissues. Its estimated incidence ranges from 1 in 40,000 to 1 in 117,000 live births. Fabry disease manifests primarily as 2 phenotypes: classic (type 1), presenting in childhood with neuropathic pain, fatigue, thermal intolerance, and early multiorgan involvement; and late onset (type 2), typically manifesting in adulthood with predominant cardiac or renal complications. Timely diagnosis requires clinical suspicion combined with enzymatic assays and genetic testing; however, atypical presentations and variability in female patients often delay recognition, underscoring the necessity for heightened clinical vigilance. Current therapeutic approaches primarily focus on enzyme replacement therapy and pharmacologic chaperones, aimed at enhancing quality of life and delaying organ dysfunction. Optimal management necessitates an individualized, multidisciplinary strategy encompassing nephrology, cardiology, genetics, clinical pharmacy, and pain management. Emerging treatments, including next-generation enzyme replacement therapies, substrate reduction therapy, gene therapy, and mRNA-based therapeutics, offer promising avenues for more effective and durable outcomes. Ongoing clinical trials and comprehensive long-term outcome studies are crucial for refining these innovative therapeutic strategies and further advancing patient care.