Objective We aim to delineate the progression of cerebellar atrophy (the primary neuroimaging finding) in children with phosphomannomutase-deficiency (PMM2-CDG) by analyzing longitudinal MRI studies and performing cerebellar volumetric analysis and a 2D cerebellar measurement. Methods Statistical analysis was used to compare MRI measurements midsagittal vermis relative diameter (MVRD) and volume of children with PMM2-CDG and sex- and age-matched controls, and to determine the rate of progression of cerebellar atrophy at different ages. Results Fifty MRI studies of 33 PMM2-CDG patients were used for 2D evaluation, and 19 MRI studies were available for volumetric analysis. Results from a linear regression model showed that patients have a significantly lower MVRD and cerebellar volume compared to controls ( p  < 0.001 and p  < 0.001 respectively). There was a significant negative correlation between age and MVRD for patients ( p  = 0.014). The rate of cerebellar atrophy measured by the loss of MVRD and cerebellar volume per year was higher at early ages ( r  = −0.578, p  = 0.012 and r  = −0.323, p  = 0.48 respectively), particularly in patients under 11 years ( p  = 0.004). There was a significant positive correlation between MVRD and cerebellar volume in PMM2-CDG patients ( r  = 0.669, p  = 0.001). Conclusions Our study quantifies a progression of cerebellar atrophy in PMM2-CDG patients, particularly during the first decade of life, and suggests a simple and reliable measure, the MVRD, to monitor cerebellar atrophy. Quantitative measurement of MVRD and cerebellar volume are essential for correlation with phenotype and outcome, natural follow-up, and monitoring in view of potential therapies in children with PMM2-CDG.