Bone Remodeling in a Mps-1h Girl after Hematopoietic Stem Cell Transplantation along with Enzymatic Replacement Therapy

Background: Mucopolysaccharidosis-1H (Hurler syndrome, MPS-1H) is the most severe form of a lysosomal storage disorder (LSD) caused by variants in IDUA, encoding alpha-L-iduronidase (IDUA). MPS-1H is also associated with various degree of skeletal defects due to the accumulation of partially degraded glycosaminoglycans (GAGs) in the lysosomes of connective tissue cells. The efficacy of hematopoietic stem cell transplantation (HSCT) and enzymatic replacement therapy (ERT) on MPS-1H skeletal manifestations are still considered not satisfactory. Case presentation: We report the case of a young girl, who manifested significant changes in bone remodeling markers and osteoclastogenesis potential after HSCT combined with ERT. She received ERT and underwent two HSCT. The skeletal alterations at the time of diagnosis, showed a trend toward improvement of both mobility and radiological features after HSCT. We observed the highest levels of Receptor activator of nuclear factor kappa-Β ligand (RANKL) and RANK/osteoprotegerin (OPG) ratio at diagnosis and during ERT, consistently with a spontaneous osteoclastogenesis. Conversely, after the successful HSCT with ongoing ERT, the highest levels of osteocalcin were observed and all markers of bone formation and resorption improved. Conclusion: The combination therapy of ERT and HSCT was effective in reduction of osteoclast activity and increasing osteoblast activity, and these changes were in keeping with the child's bone phenotype, IDUA activity and glycosaminoglycan (GAG) trends. These results represent one of the few human evidences in this context.