Hypophosphatasia is a rare heritable disorder of bone mineralization, with a spectrum of severity based on age of initial presentation. We describe the case of a 14-year-old boy with gene-confirmed inherited hypophosphatasia and growth hormone deficiency, who presented with short stature, unremarkable radiographs, and only minor physeal and metaphyseal changes on magnetic resonance (MR) imaging. Diffusion tensor imaging (DTI) before growth hormone initiation revealed abundant, non-parallel tracts in the physes and metaphyses with loss of the typical columnar organization. After 8months of growth hormone treatment, DTI scans revealed realigned, nearly parallel, longer physeal tracts; duplication of tract volume; and decreased and more typical fractional anisotropy values. DTI can thus visualize physeal tract changes over time, could be a more sensitive diagnostic technique in milder physeal abnormality cases, and may be a potential marker of growth hormone treatment response.