Mucopolysaccharidosis type I (MPSI) is an inherited metabolic disease with severe and attenuated disease subtypes. While both MPSI subtypes manifest pronounced morphological brain changes, little has been discovered about alterations of white matter (WM) microstructure. Here, we utilized rotating frame MRI contrasts along with DTI to detect WM alterations between in 11 severe and 9 attenuated MPSI patients at 3T. T1ρ and RAFF4 detected WM differences between MPS subtypes that were not depicted by DTI. Outcomes demonstrate an exceptional sensitivity of rotating frame methods to probe WM microstructure in MPSI.