Electrocardiographic Changes and Arrhythmia in Fabry Disease

Area of Science:

• Genetics and rare diseases
• Lysosomal storage disorders
• Biochemistry

Background:

• Fabry disease is an X-linked lysosomal storage disorder caused by deficient alpha-galactosidase A (a-Gal A) activity.
• This deficiency results in systemic accumulation of globotriaosylceramide (Gb3).
• While birth prevalence is cited as 1:40,000-170,000, actual patient numbers remain unclear.

Purpose of the Study:

• To summarize the current understanding of Fabry disease pathophysiology.
• To highlight the multisystemic nature of the disease and its severe complications.
• To discuss the proposed mechanisms underlying cardiac dysfunction in Fabry disease.

Main Methods:

• Literature review and synthesis of existing research on Fabry disease.
• Analysis of studies detailing Gb3 accumulation in various cell types.
• Review of recent findings on cardiac involvement and its molecular basis.

Main Results:

• Globotriaosylceramide (Gb3) accumulates in vascular endothelial cells, smooth muscle cells, cardiomyocytes, and cardiac conduction tissue.
• Disease progression leads to life-threatening complications including renal failure, cardiovascular dysfunction, neuropathy, and stroke.
• Cardiac dysfunction may involve increased nitric oxide production, oxidative damage, and electrical instability.

Conclusions:

• Fabry disease is a progressive, multisystem disorder with significant morbidity and reduced life expectancy.
• Gb3 accumulation is a hallmark, driving cellular and vascular dysfunction.
• Further research into cardiac mechanisms is crucial for understanding and managing Fabry disease.