scholarly journals Early Diagnosis and Results of Enzyme Replacement Therapy in the Patient with Mucopolysaccharidosis Type VI: Clinical Case

2021 ◽  
Author(s):  
Dmitry V. Ivanov ◽  
Anna I. Ostrun ◽  
Vladimir M. Kenis ◽  
Tatiana V. Markova ◽  
Ekaterina Yu. Zakharova
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Clinical Case ◽  
Mucopolysaccharidosis Type ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mucopolysaccharidosis Type Vi ◽  
Mps Vi ◽  
Arylsulfatase B ◽  
Arsb Gene

Background. Mucopolysaccharidosis type VI (MPS VI, Maroteaux–Lamy syndrome) is rare autosomal-recessive multisystem disease, one of the group of lysosomal storage diseases. The MPS VI pathogenesis is determined by arylsulfatase B enzyme deficiency caused by mutations in the ARSB gene. There are only few published clinical examples of this disease that covers the results of early enzyme replacement therapy (ERT) onset.Clinical case description. The child was suspected to have lysosomal storage disease at the age of 1.5 months, it was based on microscopic analysis of blood smears: Alder abnormality was revealed (granulations and red-violet inclusions in neutrophils, monocytes, lymphocytes cytoplasm). The diagnosis was confirmed at the age of 3 months: increased glycosaminoglycans (GAGs) concentration in the urine, arylsulfatase B activity decrease in dried blood spots, and pathogenic variant c.943C>T (p. R315X) in the ARSB gene in homozygous state were revealed. ERT with galsulfase was started at the age of 7 months. There was decrease in excretion of GAGs in urine to normal level after 9 and 15 months of therapy. Normal growth and body proportions for the patient’s age were determined 3 years after continuous ERT. However, there was progression of multiple dysostosis and joint stiffness, as well as eyes lesion.Conclusion. Early ERT onset cannot completely stop MPS VI progression but it allows to reduce the severity of several symptoms and improves patient’s quality of life.

Thrombocytopenia associated with galsulfase treatment

2010 ◽  
Vol 30 (7) ◽  
pp. 768-771 ◽  
Author(s):  
Murat Doğan ◽  
Yasar Cesur ◽  
Erdal Peker ◽  
Ahmet F Oner ◽  
Sekibe Zehra Dogan
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Lysosomal Storage Disorder ◽  
Mucopolysaccharidosis Type ◽  
Lysosomal Storage ◽  
Cultured Fibroblasts ◽  
Enzyme Replacement ◽  
Mucopolysaccharidosis Type Vi ◽  
Mps Vi ◽  
Arylsulfatase B

Mucopolysaccharidosis type VI (MPS VI), or Maroteaux-Lamy syndrome, is a lysosomal storage disorder that results from a deficiency of the enzyme N-acetylgalactosamine-4-sulfatase or arylsulfatase B (ASB). It is a relatively rare disorder, with an estimated incidence of 1 in 248,000 to 1 in 300,000. The diagnosis is made on the basis of findings of elevated urine glycosaminoglycans and a deficiency of ASB activity in leukocytes or cultured fibroblasts. In treatment of MPS VI, enzyme replacement therapy (galsulfase; human recombinant ASB enzyme) became available. Infusions of galsulfase were generally well tolerated. But in some patients, infusion-associated reactions including rash, urticaria, headache, hypotension, nausea, and vomiting were documented and were managed successfully by interrupting or slowing the rate of infusion and/or by the administration of antihistamines, antipyretics, corticosteroids, or oxygen. Here, we report a case with MPS VI who developed thrombocytopenia after third dose of therapy. To the best of our knowledge, this is the first report about thrombocytopenia associated with galsulfase therapy in the literature. Additionally, with this report, we want to share our approach for this case.

scholarly journals Gasser cell: A biomarker of response to enzyme replacement therapy in patients with mucopolysaccharidosis type VI

2021 ◽  
Vol 10 (5) ◽  
pp. e24510514726
Author(s):  
Márcio Antonio Wanderley de Melo ◽  
Marcelo Soares Kertenetzky ◽  
Cristina Magalhães da Silveira ◽  
Maíra Magalhães Ribeiro ◽  
Gabriela da Silva Arcanjo ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Storage Disease ◽  
Mucopolysaccharidosis Type ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mucopolysaccharidosis Type Vi ◽  
Cell Counts ◽  
Before And After ◽  
Complete Cell

The mucopolysaccharidosis (MPS) type VI is a rare lysosomal storage disease presenting leukocyte inclusions (Alder-Reilly anomaly) and lymphocytes with metachromatic inclusion surrounded by clear spaces, Gasser cells. Currently, an enzyme replacement therapy (ERT) with galsulfase is used to treat MPS type VI. This study evaluated 14 patients with MPS type VI performed cell counts Gasser before and after six months from the beginning of ERT. It was observed an average of 12.7% cells per patient, and after six months was found complete cell Gasser disappearance, proving to be an effective biomarker of response to ERT.

scholarly journals Enzyme replacement therapy in mice lacking arylsulfatase B targets bone-remodeling cells, but not chondrocytes

2020 ◽  
Vol 29 (5) ◽  
pp. 803-816 ◽  
Author(s):  
Gretl Hendrickx ◽  
Tatyana Danyukova ◽  
Anke Baranowsky ◽  
Tim Rolvien ◽  
Alexandra Angermann ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Bone Remodeling ◽  
Cell Types ◽  
Skeletal Growth ◽  
Enzyme Replacement ◽  
Mps Vi ◽  
Arylsulfatase B ◽  
The Impact ◽  
Deficient Mice

Abstract Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting the skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal growth. In the present study, we treated them by weekly injection of recombinant human ARSB (rhARSB) to analyze the impact of enzyme replacement therapy (ERT) on skeletal growth and bone remodeling. We found that all bone-remodeling abnormalities of Arsb-deficient mice were prevented by ERT, whereas chondrocyte defects were not. Likewise, histologic analysis of the surgically removed femoral head from an ERT-treated MPS-VI patient revealed that only chondrocytes were pathologically affected. Remarkably, a side-by-side comparison with other cell types demonstrated that chondrocytes have substantially reduced capacity to endocytose rhARSB, together with low expression of the mannose receptor. We finally took advantage of Arsb-deficient mice to establish quantification of chondroitin sulfation for treatment monitoring. Our data demonstrate that bone-remodeling cell types are accessible to systemically delivered rhARSB, whereas the uptake into chondrocytes is inefficient.

Effect of enzyme replacement therapy on bone formation in a feline model of mucopolysaccharidosis type VI

Bone ◽  
1997 ◽  
Vol 21 (5) ◽  
pp. 425-431 ◽  
Author(s):  
S. Byers ◽  
J.D. Nuttall ◽  
A.C. Crawley ◽  
J.J. Hopwood ◽  
K. Smith ◽  
...  
Keyword(s):  
Bone Formation ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Mucopolysaccharidosis Type ◽  
Enzyme Replacement ◽  
Mucopolysaccharidosis Type Vi ◽  
Feline Model
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