Two diseases presenting only as cardiac hypertrophy: differences between the late-onset Fabry disease cardiac variant and hypertrophic cardiomyopathy

Cardiac involvement is the leading cause of death in Fabry disease (FD), but the “cardiac variant” is often misdiagnosed as hypertrophic cardiomyopathy (HCM). This study systematically compared late-onset FD cardiac variant and HCM across clinical, electrocardiographic (ECG), echocardiographic and cardiac magnetic resonance (CMR) features to improve diagnostic accuracy. The clinical data, ECG, echocardiography, CMR (performed in 22 FD patients and 43 HCM patients), α-galactosidase A (α-Gal A) activity and globotriaosylsphingosine (Lyso-GL-3) levels of 30 proband patients with late-onset FD cardiac variant and 43 HCM patients, enrolled in Fujian, China from May 2022 to March 2024, were retrospectively analyzed. Among the FD patients, 96.7% carried the IVS4 + 919G > A mutation. ECG further revealed a significantly higher proportion of bundle branch block (BBB) (P = 0.003), prolonged P-wave duration (P = 0.043) and prolonged QRS duration (P = 0.002) in the FD patients. In addition, echocardiography showed greater left ventricular posterior wall thickness (LVPWT) (P < 0.001), higher relative wall thickness (RWT) (P < 0.001), lower left ventricular wall asymmetry (LVWa) ( P = 0.012) as well as a higher prevalence of concentric left ventricular hypertrophy (LVH) in FD patients compared with HCM ones (P = 0.005). Finally, CMR showed that late-onset FD cardiac variants had a higher proportion of late-gadolinium enhancement (LGE) in the basal inferolateral wall (P = 0.005), along with significantly lower native global T1 values (P < 0.001) and midventricular septal T1 values (P < 0.001) compared with both HCM patients and normal controls. Overall, 31.8% (7/22) of FD patients were classified as being in the late stage. In Fujian, China, late-onset FD cardiac variant was found to be predominantly characterized by the IVS4 + 919G > A mutation, with most patients presenting in the late stage. In clinical practice, the presence of unexplained concentric, symmetric LVH, together with P-QRS interval prolongation or BBB and/or reduced T1 values, should prompt screening for late-onset FD cardiac variant to avoid misdiagnosis as HCM.