Clinical characteristics of late-onset cardiac variant Fabry disease associated with the IVS4 + 919G > A mutation in Fujian, China: a cross-sectional survey

Le résumé fourni par la source

Background and purpose: Late-onset cardiac variant Fabry disease (FD), a subtype of FD, primarily manifests as cardiac involvement and is a major cause of mortality among patients with FD. This study aimed to elucidate the genetic and clinical characteristics of patients with late-onset cardiac variant FD harboring the IVS4 + 919G > A mutation in Fujian, China, to enhance clinical awareness and facilitate early recognition of this condition. Methods: A total of 636 patients presenting with unexplained left ventricular hypertrophy (LVH) were screened using dried blood spot testing in the Department of Cardiology between June 2022 and May 2025. Screening included the identification of genetic mutations, measurement of α-galactosidase A (α-GalA) enzymatic activity and Lyso-GL-3 levels, and electrocardiographic (ECG) and echocardiographic evaluations. Results: Among the 636 screened patients, GLA gene mutations were identified in 93 cases (14.6%). Of these, 91 individuals (97.8%) carried the IVS4 + 919G > A variant, and 56 probands were confirmed to have late-onset cardiac variant FD. Male patients demonstrated significantly lower α-GalA activity and higher Lyso-GL-3 concentrations than female patients (both P < 0.001). The predominant ECG abnormalities were prolonged conduction times, including prolonged P-wave duration, QRS complex, and QT interval in 55.4% (31/56), 42.9% (24/56), and 39.3% (22/56) of patients, respectively; bundle branch block was observed in 58.9% (33/56). Echocardiographic assessment of the 56 probands revealed an increased left ventricular mass index (LVMI) of 168.5 g/m 2 (range: 125.7–213.3 g/m 2 ) and relative wall thickness (RWT) of 0.58 (range: 0.51–0.77). The left ventricular wall asymmetry (LVWa) was 1.30 (range: 1.07–1.56). Correlation analysis indicated a significant positive association between age and Lyso-GL-3 levels in male patients (r = 0.435, P = 0.004). In female patients, Lyso-GL-3 levels were positively correlated with both LVMI (r = 0.630, P = 0.018) and RWT (r = 0.670, P = 0.011). Conclusions: The IVS4 + 919G > A mutation is the predominant variant in patients with late-onset cardiac variant FD in Fujian, China. These patients typically exhibit concentric and relatively symmetric LVH, while ECG findings are characterized by prolonged conduction times, particularly bundle branch block.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.