ISSN  2587-2362  |  E-ISSN  2618-642X
International Journal of Medical Biochemistry Multiplexed tandem mass spectrometry-based screening for five lysosomal storage disorders: A pilot study [Int J Med Biochem ]
Int J Med Biochem . 2020; 3(2): 73-81 | DOI: 10.14744/ijmb.2020.36449

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

Rita Christopher1, Manjunath Supriya1, Chandra Sadanandavalli Retnaswami2
1Department of Neurochemistry, National Institute of Mental Health And Neuro Sciences, Bengaluru, India
2Department of Neurology, National Institute of Mental Health And Neuro Sciences, Bengaluru, India

INTRODUCTION: 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.
RESULTS: A standard calibration curve demonstrated good linearity for each enzyme. No positive case was detected among the 12,559 putatively normal subjects tested.
DISCUSSION AND 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.

Keywords: Dried blood spots, lysosomal storage disorders, screening, tandem mass spectrometry

Rita Christopher, Manjunath Supriya, Chandra Sadanandavalli Retnaswami. Multiplexed tandem mass spectrometry-based screening for five lysosomal storage disorders: A pilot study. Int J Med Biochem . 2020; 3(2): 73-81

Corresponding Author: Rita Christopher, India
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