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

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.

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