Background and Purpose: We used diffusion MRI to investigate the structural brain connectivity networks in juvenile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disease of the childhood. Although changes in conventional MRI are typically not visually apparent under the age of ten, we previously found significant microstructural abnormalities by using diffusion MRI. Therefore, we hypothesized that the structural connectivity networks would also be affected in the disease. Materials and Methods: We acquired diffusion MRI data from 14 children with juvenile neuronal ceroid lipofuscinosis (mean age 9.6±3.4 years; 10 boys) and 14 control subjects (mean age 11.2±2.3 years; 7 boys). A follow-up MRI was performed for 12 of the patients (mean age 11.4±3.2, 8 boys). We used graph theoretical analysis to investigate the global and local properties of the structural brain connectivity networks reconstructed with constrained spherical deconvolution based whole-brain probabilistic tractography. Results: We found significantly increased characteristic path length (P=0.003) and decreased degree (P=0.003) suggesting decreased network integration and centrality in children with juvenile neuronal ceroid lipofuscinosis. The findings were similar for the follow-up MRI, and there were no significant differences between the two acquisitions of the patients. In addition, we found that the disease severity correlated negatively (P<0.05/7) with integration, segregation, centrality, and small-worldness of the networks. Moreover, we found significantly (P<0.05/164) decreased local efficiency in the left supramarginal gyrus and temporal plane and decreased strength in the right lingual gyrus. Conclusion: We found significant global and local network alterations in juvenile neuronal ceroid lipofuscinosis correlating with the disease severity, and in areas related to the symptomatology.