Abstract Classic infantile Pompe disease is caused by abnormal lysosomal glycogen accumulation in multiple tissues, including the brain due to a deficit in acid α-glucosidase (GAA). Although treatment with recombinant human GAA (rhGAA) has dramatically improved survival, rhGAA does not reach the brain, and surviving classic infantile Pompe patients develop progressive cognitive deficits and white matter (WM) lesions. We investigated the feasibility of measuring non-invasively glycogen buildup and other metabolic alterations in the brain of classic infantile Pompe patients. Four classic infantile patients (8-16yo) and 4 age-matched healthy controls (HC) were scanned on a 7T MRI scanner. We used T2-weighted MRI to assess the presence of WM lesions as well as 1H magnetic resonance spectroscopy (MRS) and MRS imaging (MRSI) to obtain the neurochemical profile and its spatial distribution, respectively. All patients had widespread WM lesions on T2-weighted images. MRS data from a single volume-of-interest positioned in the periventricular WM showed a clear shift in the neurochemical profile, particularly, a significant increase in glycogen (result of GAA deficiency) and decrease in NAA (marker of neuronal damage) in patients. MRSI results were in line and showed a widespread accumulation of glycogen and a significant lower level of NAA in patients. Our results illustrate the unique potential of 1H MRS(I) to provide a non-invasive readout of the disease pathology in the brain. Further study will assess its potential to monitor disease progression and the correlation with cognitive decline.