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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.