Detection of Mucopolysaccharidosis III-A (Sanfilippo Syndrome-A) in Dried Blood Spots (DBS) by Tandem Mass Spectrometry

Overview

Journal Mol Genet Metab

Specialty Endocrinology

Date 2018 Jul 15

PMID 30006231

Citations 9

Authors

Fan Yi

Xinying Hong

Arun Babu Kumar

Chengli Zong

Geert-Jan Boons

C Ronald Scott

Frantisek Turecek

Bruce H Robinson

Michael H Gelb

Affiliations

Soon will be listed here.

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.

Citing Articles

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Endogenous, non-reducing end glycosaminoglycan biomarkers are superior to internal disaccharide glycosaminoglycan biomarkers for newborn screening of mucopolysaccharidoses and GM1 gangliosidosis.

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Liquid Chromatography-Tandem Mass Spectrometry in Newborn Screening Laboratories.

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Tandem Mass Spectrometry Enzyme Assays for Multiplex Detection of 10-Mucopolysaccharidoses in Dried Blood Spots and Fibroblasts.

Khaledi H, Gelb M Anal Chem. 2020; 92(17):11721-11727.

PMID: 32786498 PMC: 8026088. DOI: 10.1021/acs.analchem.0c01750.

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