Leukocyte and Dried Blood Spot Arylsulfatase A Assay by Tandem Mass Spectrometry
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
Abstract
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.