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

Background: Fabry disease (FD) is a multisystem, monogenic, X-linked storage disorder caused by mutations in the GLA gene, resulting in reduced alfa-galactosidase A enzyme activity. This effect leads to the accumulation of glycosphingolipids, particularly globotriaosylceramide, in various tissues, including the heart, kidney, vasculature, smooth muscle, and peripheral nervous system. Hemizygous males are usually more severely affected than females, in whom random inactivation of an X chromosome may lead to variable phenotype.

Summary: Among the manifestations of FD, exercise intolerance is commonly diagnosed but often underestimated, even though it significantly limits quality of life, especially in young patients. This review primarily discusses the various pathophysiological mechanisms involved in exercise intolerance in FD patients, such as altered muscle composition, compromised cardiopulmonary framework, and peripheral neuropathy. Secondarily, it explores the potential effect of available therapy, including enzyme replacement therapy and chaperone therapy (migalastat), in reducing exercise intolerance while considering the potential impact of physical activity and exercise training as adjunctive treatments.

Conclusion: Exercise intolerance has a major impact on the well-being of people with FD. Exercise training can play an important role in addition to drug therapy.