Cardiac manifestations of Fabry disease

Area of Science:

• Genetics and rare diseases
• Cardiovascular medicine
• Lysosomal storage disorders

Background:

• Fabry disease (FD) is a lysosomal storage disorder resulting from alpha-galactosidase A deficiency, leading to globotriaosylceramide accumulation.
• Fabry cardiomyopathy is the leading cause of mortality in FD patients.
• Later-onset FD variants are increasingly recognized as a significant health burden.

Purpose of the Study:

• To summarize the current understanding of Fabry disease, focusing on its pathophysiology, diagnosis, and therapeutic strategies.
• To highlight the significance of Fabry cardiomyopathy and the prevalence of later-onset FD.
• To discuss the role of genetic testing and advanced cardiac imaging in FD management.

Main Methods:

• Review of current literature on Fabry disease.
• Analysis of diagnostic tools including genetic testing, echocardiography with strain imaging, and cardiac MRI (late-enhancement, T1 mapping).
• Evaluation of existing and emerging therapeutic approaches for FD.

Main Results:

• FD is more prevalent than previously estimated, with later-onset forms posing an unrecognized burden.
• Cardiac involvement, specifically Fabry cardiomyopathy, is the primary cause of mortality.
• Genetic testing and cardiac imaging are crucial for diagnosis and monitoring.

Conclusions:

• Early diagnosis and intervention are critical for managing Fabry disease and preventing fatal cardiac complications.
• Enzyme replacement therapy and pharmacological chaperone therapy are current treatments.
• Gene therapy and substrate reduction therapy show promise as future treatment options for FD.