Background <p>Cardiac involvement of the disease is a leading cause of death and disability in Fabry disease characterized by pathological accumulation of globotriaosylceramide (Gb3) and lyso-globotriaosylceramide (lyso-Gb3) in multiple organs. In this study, we sought to investigate the electrocardiographic (ECG) changes in different clinical stages and evaluate the value of these parameters in assessing cardiac involvement.</p> Methods <p>62 patients with Fabry disease and 45 healthy controls were recruited in this study. ECG assessment, echocardiographic assessment and cardiac magnetic resonance (CMR) were recorded at rest in the same day. We divided Fabry disease patients into 4 groups according to echocardiographic assessment and CMR: Pre-detectable group, Non-hypertrophic group, Hypertrophic and pre-fibrotic group as well as Hypertrophic and fibrotic group.</p> Results <p>Our results showed that Tp-e/QT was significantly decreased and Sokolow-Lyon index was markedly increased following the development of disease. QRS width and Tp-e/QT was associated with the severity of cardiac involvement in Fabry disease.</p> Conclusions <p>Our results demonstrated that QRS width and Tp-e/QT were associated with the severity of cardiac involvement in patients with Fabry disease and contributed to define the optimal intervention timepoint and assess the severity of cardiac involvement and response to disease-specific therapies.</p>