Characterization of disease-specific chondroitin sulfate nonreducing end accumulation in mucopolysaccharidosis IVA

Roger Lawrence; Heather Prill; Preejith P. Vachali; Evan G. Adintori; Greg de Hart; Raymond Y. Wang; Barbara K. Burton; Marzia Pasquali; Brett E. Crawford

doi:10.1093/GLYCOB/CWZ109

Characterization of disease-specific chondroitin sulfate nonreducing end accumulation in mucopolysaccharidosis IVA

Roger Lawrence, Heather Prill, Preejith P. Vachali, Evan G. Adintori, Greg de Hart, Raymond Y. Wang, Barbara K. Burton, Marzia Pasquali, Brett E. Crawford

Pediatrics

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Morquio syndrome type A, also known as MPS IVA, is a rare autosomal recessive disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase, a lysosomal hydrolase critical in the degradation of keratan sulfate (KS) and chondroitin sulfate (CS). The CS that accumulates in MPS IVA patients has a disease-specific nonreducing end (NRE) terminating with N-acetyl-Dgalactosamine 6-sulfate, which can be specifically quantified after enzymatic depolymerization of CS polysaccharide chains. The abundance of N-acetyl-D-galactosamine 6-sulfate over other possible NRE structures is diagnostic for MPS IVA. Here, we describe an assay for the liberation and measurement of N-acetyl-D-galactosamine 6-sulfate and explore its application to MPS IVA patient samples in pilot studies examining disease detection, effects of age and treatment with enzyme-replacement therapy. This assay complements the existing urinary KS assay by quantifying CS-derived substrates, which represent a distinct biochemical aspect of MPS IVA. A more complete understanding of the disease could help to more definitively detect disease across age ranges and more completely measure the pharmacodynamic efficacy of therapies. Larger studies will be needed to clarify the potential value of this CS-derived substrate to manage disease in MPS IVA patients.

Original language	English (US)
Pages (from-to)	433-445
Number of pages	13
Journal	Glycobiology
Volume	30
Issue number	7
DOIs	https://doi.org/10.1093/GLYCOB/CWZ109
State	Published - 2021

Funding

R.L., G.d.H. and B.E.C. are employees of and have interest in BioMarin Pharmaceutical Inc. H.P. and E.G.A. are former employees. R.Y.W. and B.K.B. have collaborated with BioMarin Pharmaceutical Inc. during and outside of the conduct of this study. B.K.B. has received consulting fees and honoraria from BioMarin Pharmaceutical Inc. and has conducted clinical trials funded by BioMarin. P.P.V. and M.P. collaborated with BioMarin Pharmaceutical Inc. in study design, data generation and interpretation, and provided contractual services for clinical assay validation during the conduct of the study.

Keywords

Biomarker
Chondroitin sulfate
Mucopolysaccharidosis IVA
N-acetylgalactosamine-6-sulfatase

ASJC Scopus subject areas

Biochemistry

Access to Document

10.1093/GLYCOB/CWZ109

Cite this

@article{72a8122e65f249c2bfad5d0cf443e637,

title = "Characterization of disease-specific chondroitin sulfate nonreducing end accumulation in mucopolysaccharidosis IVA",

abstract = "Morquio syndrome type A, also known as MPS IVA, is a rare autosomal recessive disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase, a lysosomal hydrolase critical in the degradation of keratan sulfate (KS) and chondroitin sulfate (CS). The CS that accumulates in MPS IVA patients has a disease-specific nonreducing end (NRE) terminating with N-acetyl-Dgalactosamine 6-sulfate, which can be specifically quantified after enzymatic depolymerization of CS polysaccharide chains. The abundance of N-acetyl-D-galactosamine 6-sulfate over other possible NRE structures is diagnostic for MPS IVA. Here, we describe an assay for the liberation and measurement of N-acetyl-D-galactosamine 6-sulfate and explore its application to MPS IVA patient samples in pilot studies examining disease detection, effects of age and treatment with enzyme-replacement therapy. This assay complements the existing urinary KS assay by quantifying CS-derived substrates, which represent a distinct biochemical aspect of MPS IVA. A more complete understanding of the disease could help to more definitively detect disease across age ranges and more completely measure the pharmacodynamic efficacy of therapies. Larger studies will be needed to clarify the potential value of this CS-derived substrate to manage disease in MPS IVA patients.",

keywords = "Biomarker, Chondroitin sulfate, Mucopolysaccharidosis IVA, N-acetylgalactosamine-6-sulfatase",

author = "Roger Lawrence and Heather Prill and Vachali, {Preejith P.} and Adintori, {Evan G.} and {de Hart}, Greg and Wang, {Raymond Y.} and Burton, {Barbara K.} and Marzia Pasquali and Crawford, {Brett E.}",

note = "Funding Information: R.L., G.d.H. and B.E.C. are employees of and have interest in BioMarin Pharmaceutical Inc. H.P. and E.G.A. are former employees. R.Y.W. and B.K.B. have collaborated with BioMarin Pharmaceutical Inc. during and outside of the conduct of this study. B.K.B. has received consulting fees and honoraria from BioMarin Pharmaceutical Inc. and has conducted clinical trials funded by BioMarin. P.P.V. and M.P. collaborated with BioMarin Pharmaceutical Inc. in study design, data generation and interpretation, and provided contractual services for clinical assay validation during the conduct of the study. Publisher Copyright: {\textcopyright} The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]",

year = "2021",

doi = "10.1093/GLYCOB/CWZ109",

language = "English (US)",

volume = "30",

pages = "433--445",

journal = "Glycobiology",

issn = "0959-6658",

publisher = "Oxford University Press",

number = "7",

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TY - JOUR

T1 - Characterization of disease-specific chondroitin sulfate nonreducing end accumulation in mucopolysaccharidosis IVA

AU - Lawrence, Roger

AU - Prill, Heather

AU - Vachali, Preejith P.

AU - Adintori, Evan G.

AU - de Hart, Greg

AU - Wang, Raymond Y.

AU - Burton, Barbara K.

AU - Pasquali, Marzia

AU - Crawford, Brett E.

N1 - Funding Information: R.L., G.d.H. and B.E.C. are employees of and have interest in BioMarin Pharmaceutical Inc. H.P. and E.G.A. are former employees. R.Y.W. and B.K.B. have collaborated with BioMarin Pharmaceutical Inc. during and outside of the conduct of this study. B.K.B. has received consulting fees and honoraria from BioMarin Pharmaceutical Inc. and has conducted clinical trials funded by BioMarin. P.P.V. and M.P. collaborated with BioMarin Pharmaceutical Inc. in study design, data generation and interpretation, and provided contractual services for clinical assay validation during the conduct of the study. Publisher Copyright: © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]

PY - 2021

Y1 - 2021

N2 - Morquio syndrome type A, also known as MPS IVA, is a rare autosomal recessive disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase, a lysosomal hydrolase critical in the degradation of keratan sulfate (KS) and chondroitin sulfate (CS). The CS that accumulates in MPS IVA patients has a disease-specific nonreducing end (NRE) terminating with N-acetyl-Dgalactosamine 6-sulfate, which can be specifically quantified after enzymatic depolymerization of CS polysaccharide chains. The abundance of N-acetyl-D-galactosamine 6-sulfate over other possible NRE structures is diagnostic for MPS IVA. Here, we describe an assay for the liberation and measurement of N-acetyl-D-galactosamine 6-sulfate and explore its application to MPS IVA patient samples in pilot studies examining disease detection, effects of age and treatment with enzyme-replacement therapy. This assay complements the existing urinary KS assay by quantifying CS-derived substrates, which represent a distinct biochemical aspect of MPS IVA. A more complete understanding of the disease could help to more definitively detect disease across age ranges and more completely measure the pharmacodynamic efficacy of therapies. Larger studies will be needed to clarify the potential value of this CS-derived substrate to manage disease in MPS IVA patients.

AB - Morquio syndrome type A, also known as MPS IVA, is a rare autosomal recessive disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase, a lysosomal hydrolase critical in the degradation of keratan sulfate (KS) and chondroitin sulfate (CS). The CS that accumulates in MPS IVA patients has a disease-specific nonreducing end (NRE) terminating with N-acetyl-Dgalactosamine 6-sulfate, which can be specifically quantified after enzymatic depolymerization of CS polysaccharide chains. The abundance of N-acetyl-D-galactosamine 6-sulfate over other possible NRE structures is diagnostic for MPS IVA. Here, we describe an assay for the liberation and measurement of N-acetyl-D-galactosamine 6-sulfate and explore its application to MPS IVA patient samples in pilot studies examining disease detection, effects of age and treatment with enzyme-replacement therapy. This assay complements the existing urinary KS assay by quantifying CS-derived substrates, which represent a distinct biochemical aspect of MPS IVA. A more complete understanding of the disease could help to more definitively detect disease across age ranges and more completely measure the pharmacodynamic efficacy of therapies. Larger studies will be needed to clarify the potential value of this CS-derived substrate to manage disease in MPS IVA patients.

KW - Biomarker

KW - Chondroitin sulfate

KW - Mucopolysaccharidosis IVA

KW - N-acetylgalactosamine-6-sulfatase

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DO - 10.1093/GLYCOB/CWZ109

M3 - Article

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AN - SCOPUS:85086792829

SN - 0959-6658

VL - 30

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EP - 445

JO - Glycobiology

JF - Glycobiology

IS - 7

ER -

Characterization of disease-specific chondroitin sulfate nonreducing end accumulation in mucopolysaccharidosis IVA

Abstract

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Keywords

ASJC Scopus subject areas

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