Abstrakt
Fabry disease (FD) is an X-linked lysosomal storage disorder due to reduced or undetectable α-galactosidase A (AGAL-A) enzyme activity caused by pathogenic variants in the AGAL-A gene (GLA). Tissue and organ changes are caused by widespread progressive accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3).
The classical form of FD is multisystemic with cutaneous (angiokeratomas), neurological (peripheral neuropathy, premature stroke), renal (proteinuria and renal insufficiency), and cardiac involvement. Later onset variants may be limited to the heart.
The objective of this review is to summarize the current knowledge on cardiac manifestations of FD and effects of targeted therapy. Cardiac involvement is characterized by progressive hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death (SCD).
Targeted therapy is based on enzyme replacement therapy (ERT). Recently, small molecular chaperone, migalastat, became available for patients carrying amenable pathogenic GLA variants.
The management of cardiac complications requires a complex approach. Several measures differ from standard clinical guidelines.
Betablockers should be used with caution due to bradycardia risk, amiodarone avoided if possible, and anticoagulation used from the first appearance of atrial fibrillation. In Fabry cardiomyopathy SCD calculators are inappropriate.
The awareness of FD manifestations is essential for early identification of patients and timely treatment initiation.