Detection of mucopolysaccharidosis III-A (Sanfilippo Syndrome-A) in dried blood spots (DBS) by tandem mass spectrometry

Fan Yi; Xinying Hong; Arun Babu Kumar; Chengli Zong; Geert Jan Boons; C. Ronald Scott; Frantisek Turecek; Bruce H. Robinson; Michael H. Gelb

doi:10.1016/j.ymgme.2018.05.005

Detection of mucopolysaccharidosis III-A (Sanfilippo Syndrome-A) in dried blood spots (DBS) by tandem mass spectrometry

Fan Yi
, Xinying Hong
, Arun Babu Kumar
, Chengli Zong
, Geert Jan Boons
, C. Ronald Scott
, Frantisek Turecek
, Bruce H. Robinson
, Michael H. Gelb^*

^*Corresponding author for this work

University of Washington
University of Georgia
extern

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

Abstract

Background: With ongoing efforts to develop improved treatments for Sanfilippo Syndrome Type A (MPS-IIIA), a disease caused by the inability to degrade heparan sulfate in lysosomes, we sought to develop an enzymatic activity assay for the relevant enzyme, sulfamidase, that uses dried blood spots (DBS). Methods: We designed and synthesized a new sulfamidase substrate that can be used to measure sulfamidase activity in DBS using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Sulfamidase activity was readily detected in DBS using the new substrate and LC-MS/MS. Sulfamidase activity showed acceptable linearity proportional to the amount of enzyme and reaction time. Sulfamidase activity in 238 random newborns was well elevated compared to the range of activities measured in DBS from 8 patients previously confirmed to have MPS-IIIA. Conclusions: This is the first report of an assay capable of detecting sulfamidase in DBS. The new assay could be useful in diagnosis and potentially for newborn screening of MPS-IIIA.

Original language	English
Pages (from-to)	59-63
Number of pages	5
Journal	Molecular Genetics and Metabolism
Volume	125
Issue number	1-2
DOIs	https://doi.org/10.1016/j.ymgme.2018.05.005
Publication status	Published - Sept 2018
Externally published	Yes

Funding

This work was funded by a grant from the National Institutes of Health to M. H. Gelb, F. Turecek, and C. Ronald Scott ( R01 DK067859 ). Appendix A

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Dried blood spot
Enzyme deficiency
Lysosomal storage disease
Mucopolysaccharidosis III type A
Sulfamidase
Tandem mass spectrometry

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10.1016/j.ymgme.2018.05.005

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@article{397bb2b5e1f14dc1bcfd02e1da728d88,

title = "Detection of mucopolysaccharidosis III-A (Sanfilippo Syndrome-A) in dried blood spots (DBS) by tandem mass spectrometry",

abstract = "Background: With ongoing efforts to develop improved treatments for Sanfilippo Syndrome Type A (MPS-IIIA), a disease caused by the inability to degrade heparan sulfate in lysosomes, we sought to develop an enzymatic activity assay for the relevant enzyme, sulfamidase, that uses dried blood spots (DBS). Methods: We designed and synthesized a new sulfamidase substrate that can be used to measure sulfamidase activity in DBS using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Sulfamidase activity was readily detected in DBS using the new substrate and LC-MS/MS. Sulfamidase activity showed acceptable linearity proportional to the amount of enzyme and reaction time. Sulfamidase activity in 238 random newborns was well elevated compared to the range of activities measured in DBS from 8 patients previously confirmed to have MPS-IIIA. Conclusions: This is the first report of an assay capable of detecting sulfamidase in DBS. The new assay could be useful in diagnosis and potentially for newborn screening of MPS-IIIA.",

keywords = "Dried blood spot, Enzyme deficiency, Lysosomal storage disease, Mucopolysaccharidosis III type A, Sulfamidase, Tandem mass spectrometry",

author = "Fan Yi and Xinying Hong and Kumar, \{Arun Babu\} and Chengli Zong and Boons, \{Geert Jan\} and Scott, \{C. Ronald\} and Frantisek Turecek and Robinson, \{Bruce H.\} and Gelb, \{Michael H.\}",

year = "2018",

month = sep,

doi = "10.1016/j.ymgme.2018.05.005",

language = "English",

volume = "125",

pages = "59--63",

journal = "Molecular Genetics and Metabolism",

issn = "1096-7192",

publisher = "Academic Press Inc.",

number = "1-2",

}

TY - JOUR

T1 - Detection of mucopolysaccharidosis III-A (Sanfilippo Syndrome-A) in dried blood spots (DBS) by tandem mass spectrometry

AU - Yi, Fan

AU - Hong, Xinying

AU - Kumar, Arun Babu

AU - Zong, Chengli

AU - Boons, Geert Jan

AU - Scott, C. Ronald

AU - Turecek, Frantisek

AU - Robinson, Bruce H.

AU - Gelb, Michael H.

PY - 2018/9

Y1 - 2018/9

N2 - Background: With ongoing efforts to develop improved treatments for Sanfilippo Syndrome Type A (MPS-IIIA), a disease caused by the inability to degrade heparan sulfate in lysosomes, we sought to develop an enzymatic activity assay for the relevant enzyme, sulfamidase, that uses dried blood spots (DBS). Methods: We designed and synthesized a new sulfamidase substrate that can be used to measure sulfamidase activity in DBS using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Sulfamidase activity was readily detected in DBS using the new substrate and LC-MS/MS. Sulfamidase activity showed acceptable linearity proportional to the amount of enzyme and reaction time. Sulfamidase activity in 238 random newborns was well elevated compared to the range of activities measured in DBS from 8 patients previously confirmed to have MPS-IIIA. Conclusions: This is the first report of an assay capable of detecting sulfamidase in DBS. The new assay could be useful in diagnosis and potentially for newborn screening of MPS-IIIA.

AB - Background: With ongoing efforts to develop improved treatments for Sanfilippo Syndrome Type A (MPS-IIIA), a disease caused by the inability to degrade heparan sulfate in lysosomes, we sought to develop an enzymatic activity assay for the relevant enzyme, sulfamidase, that uses dried blood spots (DBS). Methods: We designed and synthesized a new sulfamidase substrate that can be used to measure sulfamidase activity in DBS using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Sulfamidase activity was readily detected in DBS using the new substrate and LC-MS/MS. Sulfamidase activity showed acceptable linearity proportional to the amount of enzyme and reaction time. Sulfamidase activity in 238 random newborns was well elevated compared to the range of activities measured in DBS from 8 patients previously confirmed to have MPS-IIIA. Conclusions: This is the first report of an assay capable of detecting sulfamidase in DBS. The new assay could be useful in diagnosis and potentially for newborn screening of MPS-IIIA.

KW - Dried blood spot

KW - Enzyme deficiency

KW - Lysosomal storage disease

KW - Mucopolysaccharidosis III type A

KW - Sulfamidase

KW - Tandem mass spectrometry

UR - https://www.scopus.com/pages/publications/85049561935

U2 - 10.1016/j.ymgme.2018.05.005

DO - 10.1016/j.ymgme.2018.05.005

M3 - Article

AN - SCOPUS:85049561935

SN - 1096-7192

VL - 125

SP - 59

EP - 63

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

IS - 1-2

ER -

Detection of mucopolysaccharidosis III-A (Sanfilippo Syndrome-A) in dried blood spots (DBS) by tandem mass spectrometry

Abstract

Funding

UN SDGs

Keywords

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