A case of cardiac involvement in Fabry disease caused by the p.D313Y variant of the GLA-gene.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to progressive sphingolipid accumulation in various tissues, including the heart. Cardiac manifestations often include left ventricular hypertrophy (LVH), myocardial fibrosis, and conduction abnormalities. The p.D313Y variant of the GLA gene is considered a milder mutation and may present with milder or without classical FD symptoms. Case summary: We report a 54-year-old male presenting with persistent fatigue and dry cough following a mild viral infection. Initial work-up showed premature atrial and ventricular contractions, stress-induced ischaemia on myocardial perfusion imaging, and mildly reduced left ventricular ejection fraction (EF). Cardiac magnetic resonance imaging (CMR) revealed focal late gadolinium enhancement (LGE) in the basal inferolateral myocardium, with normal native T1 (nT1) values. Follow-up imaging demonstrated progressive myocardial changes, including further EF reduction and decreasing nT1 values. These findings raised suspicion for FD. Genetic testing confirmed the p.D313Y variant in the GLA gene, and enzymatic analysis showed mildly reduced α-galactosidase A activity. Discussion: This case highlights myocardial involvement in p.D313Y-associated Fabry disease (vFD) in the absence of LVH or classical symptoms. CMR, particularly native T1 mapping, proved useful in identifying early myocardial changes. The findings suggest that even patients with vFD and no LVH may develop significant cardiac pathology. This case emphasizes the importance of considering FD in patients with unexplained cardiac symptoms and unremarkable coronary findings. Further research is needed to assess the potential benefits of early intervention with enzyme replacement or chaperone therapy in vFD.