Fabry disease in adults: systematic review of epidemiology, pathophysiology, diagnosis and treatment – 2025 update

Abstract

Fabry disease is an X-linked hereditary disorder caused by deficiency of the enzyme alpha-galactosidase A, leading to progressive accumulation of glycosphingolipids, especially globotriaosylceramide (Gb3), in multiple tissues. This systematic review aimed to synthesize recent evidence on epidemiology, pathophysiology, clinical manifestations, diagnosis and treatment of Fabry disease in adults, focusing on studies published between 2018 and 2025. Searches were conducted in PubMed/MEDLINE, Embase, Scopus and Cochrane Library, selecting observational studies, clinical trials, meta-analyses and international guidelines, while excluding case reports and very small series. From 2,962 initial articles, 148 were included for qualitative analysis. Findings show that prevalence is higher than previously estimated, largely due to expanded identification of late-onset variants through modern screening tools. Cardiac and renal variants predominate in adults and are frequently underdiagnosed. Advances such as cardiac magnetic resonance with T1 mapping, speckle-tracking echocardiography and biomarkers like lyso-Gb3 have improved diagnostic accuracy. Available treatments—including enzyme replacement and pharmacological chaperones—demonstrate enhanced benefit when started early, and innovative therapies such as gene therapy are promising. In conclusion, substantial progress has been made in understanding Fabry disease, enabling earlier diagnosis and more effective management, although challenges remain in personalized therapeutic approaches.