BACKGROUND: Niemann-Pick disease type C (NP-C) is a rare genetic lysosomal lipid storage disorder characterized by progressive neurological impairment. Early diagnosis is critical for initiating treatment with miglustat, which can decelerate disease progression. In this study, we evaluated a cohort of 22 NP-C patients who underwent MRI, [ RESULTS: Group-level MRI analysis identified significant cerebellar and thalamic atrophy (d = 1.56, p <
0.0001 and d = 1.09, p <
0.001, respectively), with less pronounced involvement of the frontal lobe and hippocampus, which aligned with existing neuropathological understanding and guidelines. Conversely, [ CONCLUSIONS: Our findings delineate a discernible hypometabolism pattern specific to NP-C that distinguishes it from other neurodegenerative conditions, thus suggesting that [ TRIAL REGISTRATION: XUNTA 2015/140. Registered 21 April 2015.