Systolic and diastolic dysfunction of the left ventricle are present in patients with cardiac involvement in Fabry disease. The aim of this study was to investigate the diagnostic value of the Tei index, a marker for combined diastolic and systolic function, in patients with Fabry disease.A total of 66 consecutive patients with genetically confirmed Fabry disease were included in this study. Standard echocardiography, including the Tei index, and magnetic resonance imaging were performed. Patients were followed for 2.9 ± 1.9 years; 56 patients received enzyme replacement therapy, and 10 patients had natural history follow-up. Patients were subdivided into three groups: (1) those without cardiac involvement, (2) those with left ventricular (LV) hypertrophy and without late enhancement on magnetic resonance imaging, and (3) those with late enhancement on magnetic resonance imaging.The Tei index was significantly higher in the groups 2 (0.56 ± 0.10) and 3 (0.60 ± 0.16) compared with patients without cardiac involvement (0.44 ± 0.10) (P 0.64 showed signs of cardiomyopathy. In contrast, ejection fractions were normal in all three patient groups and therefore not useful for the detection of cardiac involvement. A significant positive correlation was observed between LV wall thickness and the Tei index in the complete patient cohort. Moreover, receiver operating characteristic analysis revealed a large area under the curve for Tei index and hypertrophy, while the area under the curve for fibrosis was small. The Tei index remained unchanged in the natural history and enzyme replacement therapy groups during follow-up.In this cohort, the Tei index was of limited value to detect myocardial fibrosis and monitor enzyme replacement therapy. However, the progression of cardiomyopathy toward LV hypertrophy seems to be paralleled by global functional impairment, which can be assessed by the Tei index but not by ejection fraction. Thus, the Tei index seems to be a global parameter that can detect LV functional reduction in patients with Fabry disease.