Open AccessLeukocyte and Dried Blood Spot Arylsulfatase A Assay by Tandem Mass Spectrometry
Author(s) -
Xinying Hong,
Arun Kumar,
Jessica Daiker,
Fan Yi,
Martin Sadı́lek,
Fabiola De Mattia,
Francesca Fumagalli,
Valeria Calbi,
Roberta Damiano,
Maria Della Bona,
Giancarlo la Marca,
Adeline Vanderver,
Amy Waldman,
Laura Adang,
Omar Sherbini,
Sarah Woidill,
Teryn Suhr,
Joanne Kurtzberg,
Maria L. Beltran-Quintero,
Maria L. Escolar,
Alessandro Aiuti,
Alan Finglas,
Amber Olsen,
Michael H. Gelb
Publication year - 2020
Publication title -
analytical chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.117
H-Index - 332
eISSN - 1520-6882
pISSN - 0003-2700
DOI - 10.1021/acs.analchem.9b05274
Subject(s) - arylsulfatase a , metachromatic leukodystrophy , chemistry , dried blood spot , tandem mass spectrometry , chromatography , mass spectrometry , false positive paradox , dried blood , liquid chromatography–mass spectrometry , arylsulfatase , enzyme , biochemistry , machine learning , computer science
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays were developed to measure arylsulfatase A (ARSA) activity in leukocytes and dried blood spots (DBS) using deuterated natural sulfatide substrate. These new assays were highly specific and sensitive. Patients with metachromatic leukodystrophy (MLD) and multiple sulfatase deficiency (MSD) displayed a clear deficit in the enzymatic activity and could be completely distinguished from normal controls. The leukocyte assay reported here will be important for diagnosing MLD and MSD patients and for monitoring the efficacy of therapeutic treatments. ARSA activity was measured in DBS for the first time without an antibody. This new ARSA DBS assay can serve as a second-tier test following the sulfatide measurement in DBS for newborn screening of MLD. This leads to an elimination of most of the false positives identified by the sulfatide assay.