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Endocrine, Metabolic & Immune Disorders - Drug Targets


ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Case Report

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

Author(s): Albina Tummolo*, Giacomina Brunetti, Laura Piacente, Antonio Marzollo, Alessandra Biffi, Alberto Burlina and Maria Felicia Faienza

Volume 22, Issue 14, 2022

Published on: 05 August, 2022

Page: [1425 - 1432] Pages: 8

DOI: 10.2174/1871530322666220520121839

Price: $65


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 degrees 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 is still considered unsatisfactory.

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 HSCTs. 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 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 reducing osteoclast activity and increasing osteoblast activity, and these changes were according to the child's bone phenotype, IDUA activity, and Glycosaminoglycan (GAG) trends. These results represent one of the few pieces of human evidence in this context.

Keywords: HSCT, ERT, mps-1h, osteoclastogenesis, rankl, glycosaminoglycan.

Graphical Abstract
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