In this study, MS analysis of N-linked glycans revealed that NEU1 deficiency in HgsnatP304L and Hgsnat-Geo mice, as well as in patients with MPS I, II, and III, was associated with an overall increase in the sialylation of brain glycoproteins, which could potentially modify hippocampal synaptic transmission and plasticity. This evidence concerns the gene NEU1 and Scheie syndrome.