We investigated whether local ADC changes precede the formation of white matter lesions (WML) in patients with Fabry disease. A dataset was collected, containing five-year follow-up MRI data of 46 patients with Fabry disease. Within WMLs, ADC values were significantly higher compared to healthy WM and kept increasing after first detection. Moreover, ADC values were significantly higher within regions that were detected at later time points as WML on FLAIR images. These findings indicate that diffusion weighted imaging could play an important role in predicting which patients are at risk of lesion formation and require preemptive treatment.