How Do Physical Activity and Exercise Affect Fabry Disease? Exploring a New Opportunity

Area of Science:

• Genetics and rare diseases
• Metabolic disorders
• Cardiopulmonary health

Background:

• Fabry disease (FD) is an X-linked genetic disorder caused by mutations in the GLA gene, leading to alpha-galactosidase A deficiency.
• This deficiency results in the accumulation of glycosphingolipids, like globotriaosylceramide, in multiple organs.
• FD affects males more severely, with females exhibiting variable phenotypes due to X-chromosome inactivation.

Purpose of the Study:

• To review the pathophysiological mechanisms underlying exercise intolerance in Fabry disease.
• To explore the efficacy of current therapies (enzyme replacement and chaperone therapy) in mitigating exercise intolerance.
• To assess the role of physical activity and exercise training as complementary treatments for FD-related exercise intolerance.

Main Methods:

• Literature review focusing on the pathophysiology of exercise intolerance in FD.
• Analysis of studies investigating the impact of enzyme replacement therapy (ERT) and migalastat (chaperone therapy).
• Evaluation of research on exercise training interventions in FD patients.

Main Results:

• Exercise intolerance is a common and significant manifestation of FD, impacting patient quality of life.
• Altered muscle composition, compromised cardiopulmonary function, and peripheral neuropathy contribute to exercise intolerance in FD.
• Available therapies show potential in reducing exercise intolerance, with exercise training emerging as a beneficial adjunctive approach.

Conclusions:

• Exercise intolerance significantly affects the well-being of individuals with Fabry disease.
• Exercise training can be a crucial component of management for FD patients, complementing pharmacological treatments.