Fabry disease: Definition, Incidence, Clinical presentations and Treatment-Focus on cardiac involvement

Abstract

Fabry disease (FD) is a relatively rare X-linked hereditary disease caused by mutations in the GLA gene that results in deficient α-galactosidase A (α-Gal A) enzyme activity. The disturbed catabolism of the neutral sphingolipids globotriaosylceramide (Gb3) leads to its progressive lysosomal accumulation throughout the body. Multiple organs can be affected. The atypical late-onset cardiac variant is associated with a high burden of cardiac morbidity and mortality. The aim of this work was to present an updated overview of the FD, with focus on cardiovascular manifestations and its management. Enzyme replacement therapy (ERT) is nowadays an established treatment of FD and is recommended as early as possible with or without chaperone therapy (migalastat) to prevent or delay the progression of renal, cardiac, and cerebrovascular complications. It improves quality of life and may further result in decrease in Left ventricular (LV) mass and to some extent LV function recovery. However, LV hypertrophy (LVH) does not always respond well to ERT despite successful Gb3 clearance. Furthermore, its impact on the hard clinical events is uncertain. Some possible reasons for this apparent discrepancy are discussed. ERT may be less effective in patients who have already developed fibrosis or irreversible organ damage. However, other confounding factors may be equally important.