TY - JOUR
T1 - Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI)
T2 - A single dose of galsulfase further reduces urine glycosaminoglycans after hematopoietic stem cell transplantation
AU - Whitley, Chester B
AU - Utz, Jeanine R.Jarnes
PY - 2010/12
Y1 - 2010/12
N2 - Background: Maroteaux-Lamy syndrome, or mucopolysaccharidosis (MPS) type VI, is the autosomal recessive lysosomal disorder resulting from deficient N-acetylgalactosamine 4-sulfatase (ARSB) and the consequent accumulation of glycosaminoglycan (GAG). Patients fully engrafted after hematopoietic stem cell transplantation (HSCT) demonstrate several indicators of metabolic correction such as reduction in liver size, absence of hepatic ultrastructural pathology, and patients do not develop cervical cord compression. Engrafted patients demonstrate reduction in urine GAG achieving near-normal levels. Hypothesis: We presumed that HSCT engraftment from a normal individual would provide sufficient systemic enzyme to accomplish maximal metabolic correction, and that no additional benefit would accrue from additional therapy such as with intravenous recombinant human ARSB protein, galsulfase. Materials and methods: A 22-year-old male had received an allogeneic bone marrow transplant from an HLA-identical sibling donor, and remained fully engrafted after 20. years. In response to his request regarding the potential benefit of enzyme replacement therapy, we administered a single, standard dose of galsulfase while monitoring urine GAG daily, before and after the treatment. Results: Urine GAG declined from slightly high pre-treatment levels (7.63. mg GAG/mmol creatinine; range 7.0-8.5, N= 3) progressively declining below the age-specific normal range (< 6.5) over 10. days to the lowest level of 4.4, with a mean post-treatment level of 5.60 (N= 10). Conclusions: Somewhat surprisingly, the biomarker urine GAG was significantly reduced after a single treatment of intravenous galsulfase thus suggesting that supplemental enzyme replacement therapy might improve the clinical outcome for donor-engrafted patients with MPS VI.
AB - Background: Maroteaux-Lamy syndrome, or mucopolysaccharidosis (MPS) type VI, is the autosomal recessive lysosomal disorder resulting from deficient N-acetylgalactosamine 4-sulfatase (ARSB) and the consequent accumulation of glycosaminoglycan (GAG). Patients fully engrafted after hematopoietic stem cell transplantation (HSCT) demonstrate several indicators of metabolic correction such as reduction in liver size, absence of hepatic ultrastructural pathology, and patients do not develop cervical cord compression. Engrafted patients demonstrate reduction in urine GAG achieving near-normal levels. Hypothesis: We presumed that HSCT engraftment from a normal individual would provide sufficient systemic enzyme to accomplish maximal metabolic correction, and that no additional benefit would accrue from additional therapy such as with intravenous recombinant human ARSB protein, galsulfase. Materials and methods: A 22-year-old male had received an allogeneic bone marrow transplant from an HLA-identical sibling donor, and remained fully engrafted after 20. years. In response to his request regarding the potential benefit of enzyme replacement therapy, we administered a single, standard dose of galsulfase while monitoring urine GAG daily, before and after the treatment. Results: Urine GAG declined from slightly high pre-treatment levels (7.63. mg GAG/mmol creatinine; range 7.0-8.5, N= 3) progressively declining below the age-specific normal range (< 6.5) over 10. days to the lowest level of 4.4, with a mean post-treatment level of 5.60 (N= 10). Conclusions: Somewhat surprisingly, the biomarker urine GAG was significantly reduced after a single treatment of intravenous galsulfase thus suggesting that supplemental enzyme replacement therapy might improve the clinical outcome for donor-engrafted patients with MPS VI.
KW - BMT
KW - Bone marrow transplantation
KW - ERT
KW - Enzyme replacement therapy
KW - GAG
KW - Galsulfase
KW - Glycosaminoglycan
KW - MPS
KW - MTM
KW - Maroteaux-Lamy syndrome
KW - Medication therapy management
KW - Metabolic correction
KW - Mucopolysaccharidosis
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U2 - 10.1016/j.ymgme.2010.07.015
DO - 10.1016/j.ymgme.2010.07.015
M3 - Article
C2 - 20800524
AN - SCOPUS:78649323110
SN - 1096-7192
VL - 101
SP - 346
EP - 348
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 4
ER -