The Cardiovascular Phenotype in Fabry Disease: New Findings in the Research Field

Fabry disease (FD) is a lysosomal storage disorder, depending on defects in alpha-galactosidase A (GAL) activity. At the clinical level, FD shows a high phenotype variability. Among them, cardiovascular dysfunction is often recurrent or, in some cases, is the sole symptom (cardiac variant) representing the leading cause of death in Fabry patients. The existing therapies, besides specific symptomatic treatments, are mainly based on the restoration of GAL activity. Indeed, mutations of the galactosidase alpha gene (GLA) cause a reduction or lack of GAL activity leading to globotriaosylceramide (Gb3) accumulation in several organs. However, several other mechanisms are involved in FD's development and progression that could become useful targets for therapeutics. This review discusses FD's cardiovascular phenotype and the last findings on molecular mechanisms that accelerate cardiac cell damage.

Automated summary

Fabry disease is a lysosomal storage disorder caused by defects in alpha-galactosidase A activity, leading to a high variability in clinical presentation. Cardiovascular dysfunction is a common symptom and a leading cause of death in patients, with therapy focused on restoring GAL activity. Other mechanisms are also involved in the disease's development, potentially serving as useful therapeutic targets.