The Heart in Fabry Disease: Mechanisms Beyond Storage and Forthcoming Therapies

Area of Science:

• Cardiology
• Genetics
• Biochemistry

Background:

• Cardiovascular involvement is a primary cause of mortality and morbidity in Fabry disease (FD).
• Left ventricular hypertrophy is a hallmark of cardiac involvement in FD, though glycolipid storage affects all cardiac cells.
• Lysosomal globotriasylceramide accumulation initiates cardiac damage, with secondary pathways exacerbating progression.

Purpose of the Study:

• To elucidate the complex pathophysiology of cardiac damage in Fabry disease.
• To identify novel therapeutic targets beyond direct lysosomal storage.
• To inform the development of additional cardiovascular therapies for FD patients.

Main Methods:

• Review of existing literature on Fabry disease cardiac pathophysiology.
• Analysis of cellular and tissue damage mechanisms in FD.
• Evaluation of current and emerging therapeutic strategies.

Main Results:

• Early cardiac damage in FD is driven by globotriasylceramide accumulation.
• Advanced stages involve secondary pathways including impaired energy production, inflammation, and cell death.
• These secondary mechanisms limit the efficacy of current FD-specific treatments.

Conclusions:

• Comprehensive understanding of FD cardiac pathophysiology is crucial.
• Therapeutic strategies should address both glycolipid storage and secondary damage pathways.
• Development of novel treatments targeting these complex mechanisms is warranted.