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

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.

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

Вопросы современной педиатрии ◽

10.15690/vsp.v20i6s.2369 ◽

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.

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Thrombocytopenia associated with galsulfase treatment

Human & Experimental Toxicology ◽

10.1177/0960327110379023 ◽

2010 ◽

Vol 30 (7) ◽

pp. 768-771 ◽

Cited By ~ 4

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.

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