Multiplexed tandem mass spectrometry-based screening for five lysosomal storage disorders: A pilot study

This is the authors' abstract. We don't add key points for this paper.

Objectives:The need for early detection of lysosomal storage diseases (LSDs) for which therapeutic options are available makes them attractive candidate disorders to perform high-throughput population screening.This is a pilot study designed to simultaneously screen for Krabbe, Niemann-Pick types A/B, Fabry, Gaucher and Pompe diseases in putatively normal Indian subjects, using dried blood spots and a liquid chromatography-tandem mass spectrometry method.Methods: Blood spots from 12,559 putatively normal subjects were used to measure 5 lysosomal enzymes: galactocerebrosidase, acid sphingomyelinase, α-galactosidase, β-glucocerebrosidase, and α-glucosidase.From each blood spot, 3.2-mm punches were extracted and incubated using specific substrates and internal standards.After several liquid-and solid-phase extraction steps, the resulting solution was reconstituted and injected into a triple quadrupole, liquid chromatography-tandem mass spectrometer after recombining the reaction products into a single 96-well plate.Results: A standard calibration curve demonstrated good linearity for each enzyme.No positive case was detected among the 12,559 putatively normal subjects tested.Conclusion: Tandem mass spectrometry technology makes it possible to perform high-throughput screening to identify LSDs using blood spots.Further large-scale studies to determine the population prevalence and incidence of these disorders are warranted.