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Plasmatic and Urinary Glycosaminoglycans Characterization in Mucopolysaccharidosis II Patient Treated with Enzyme-Replacement Therapy with Idursulfase

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Book cover JIMD Reports - Case and Research Reports, 2012/1

Part of the book series: JIMD Reports ((JIMD,volume 4))

Abstract

We report the structural characterization of plasmatic and urinary GAGs in a patient affected by MPS II (Hunter syndrome) before and during the first 10 months of enzyme-replacement therapy (ERT). Plasmatic GAGs before ERT were rich in pathological DS consisting of iduronic acid (IdoA) and composed of ~90% ΔDi4s and trace amounts of disulfated disaccharides. DS was also characterized as the main (~90%) urinary GAG mainly composed of ~90% ΔDi4s with minor percentages of monosulfated and disulfated disaccharides, in particular ΔDi2,4dis. After 300 days of ERT, plasmatic DS strongly decreased but ~14% of IdoA-rich ΔDi4s was still detected. Similarly, urinary galactosaminoglycans were mainly composed of 78% ΔDi4s, ~11% ΔDi6s and ~4% ΔDi0s with the persistence of ΔDi2,4dis (~4%). About 40% of IdoA-formed ΔDi4s were also calculated, thus confirming that pathological DS is still present in excreted urinary GAGs during ERT. By considering the % of IdoA, we observed rather similar kinetics of excretion in fluids from the beginning of the treatment. Immediately after the first enzyme infusion, a large amount of abnormal DS is removed from tissues reaching the blood compartment and eliminated via the urine, and this process lasts for about 2 weeks. After this, the percentage of IdoA-rich material present in biological fluids remains fairly constant over the following 9 months of treatment. To date, these are the first data regarding plasmatic and urinary kinetics directly measured on products released by the activity of the recombinant enzyme Idursulfase, iduronate-2-sulfatase, evaluated using specific and sensitive analytical procedures.

Competing interests: None declared.

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Abbreviations

ΔDi0s:

ΔUA-(1→3)-GalNAc

ΔDi2,4dis,ΔDi-dis B:

ΔUA-2s-(1→3)-GalNAc-4s

ΔDi2,6dis,ΔDi-dis D:

ΔUA-2s-(1→3)-GalNAc-6s

ΔDi4,6dis,ΔDi-dis E:

ΔUA-(1→3)-GalNAc-4,6dis

ΔDi4s:

ΔUA-(1→3)-GalNAc-4s

ΔDi6s:

ΔUA-(1→3)-GalNAc-6s

CETAB:

Cetyltrimethyl-ammonium bromide

CS:

Chondroitin sulfate

DMB:

1,9-Dimethylmethylene blue

DS:

Dermatan sulfate

ERT:

Enzyme-replacement therapy

GAG:

Glycosaminoglycan

GlcA:

Glucuronic acid

HS:

Heparan sulfate

IdoA:

Iduronic acid

MPS:

Mucopolysaccharidoses

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Author information

Authors and Affiliations

  1. Pediatric Division, Department of Clinical Sciences, Polytechnic University of the Marche, Ospedali Riuniti, Presidio Salesi, Ancona, Italy

    Giovanni V. Coppa, Lucia Zampini, Lucia Santoro, Tiziana Galeazzi & Orazio Gabrielli

  2. Department of Biology, University of Modena and Reggio Emilia, Via Campi 213/D, 41100, Modena, Italy

    Dania Buzzega, Francesca Maccari, Fabio Galeotti & Nicola Volpi

Authors
  1. Giovanni V. Coppa
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  2. Dania Buzzega
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  3. Lucia Zampini
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  4. Francesca Maccari
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  5. Lucia Santoro
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  6. Fabio Galeotti
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  7. Tiziana Galeazzi
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  8. Orazio Gabrielli
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  9. Nicola Volpi
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Corresponding author

Correspondence to Nicola Volpi .

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    Additional information

    Communicated by: Verena Peters

    Appendices

    Contributors

    N.V. developed the applied methodologies. D.B., L.Z., F.M., L.S., F.G. and T.G. performed the experimental procedures and analyses. N.V., G.V.C. and O.G. designed and developed the experimental design, performed data analysis and wrote the manuscript.

    All authors reviewed and approved the study.

    Conflict of Interest

    We declare that we have no conflict of interest.

    Grant Support

    Research partially supported by Fondazione Marco Mancini onlus, Fabriano, Ancona, Italy.

    The Concise Sentence Take-Home Message

    Before ERT and over 10 months of enzyme infusion, glycosaminoglycans in urine and plasma were analyzed in a patient with severe MPS II (Hunter syndrome) and new data and a better understanding of the metabolic fate of these macromolecules have been obtained.

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    © 2011 SSIEM and Springer-Verlag Berlin Heidelberg

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    Coppa, G.V. et al. (2011). Plasmatic and Urinary Glycosaminoglycans Characterization in Mucopolysaccharidosis II Patient Treated with Enzyme-Replacement Therapy with Idursulfase. In: JIMD Reports - Case and Research Reports, 2012/1. JIMD Reports, vol 4. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_75

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    • DOI: https://doi.org/10.1007/8904_2011_75

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    • Publisher Name: Springer, Berlin, Heidelberg

    • Print ISBN: 978-3-642-25751-3

    • Online ISBN: 978-3-642-25752-0

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