Longevity & AgingFabry Disease Triggers Atrial Arrhythmia Before Heart Enlargement Begins
Fabry disease (FD), a rare genetic lysosomal storage disorder, causes dangerous heart rhythm problems earlier than previously recognized. Researchers analyzed ECGs from 115 FD patients and discovered P-wave shortening and increased atrial fibrillation (AF) risk even before cardiomyopathy develops. Using CRISPR-edited stem cells carrying the most common UK FD mutation (GLA p.N215S), they created the first atrial cardiomyocyte FD model, revealing abnormal electrical activity, calcium mishandling, and increased spontaneous firing. Computer simulations confirmed these cellular changes produce the ECG patterns seen in early FD and increase AF susceptibility. The findings suggest atrial remodeling is a primary, early driver of arrhythmia in FD, potentially preceding and independent of ventricular changes.
