A highly multiplexed biochemical assay for analytes in dried blood spots: application to newborn screening and diagnosis of lysosomal storage disorders and other inborn errors of metabolism

Genet Med. 2020 Jul;22(7):1262-1268. doi: 10.1038/s41436-020-0790-9. Epub 2020 Apr 20.

Abstract

Purpose: To develop a multiplexed assay for the newborn screening of lysosomal storage disorders and additional inborn errors in a flexible, comprehensive, and affordable manner to keep up with the expansion of the newborn screening panel.

Methods: Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was chosen as the detection platform for its superiority compared to traditional flow-injection MS/MS.

Results: A high-throughput, 18-plex UPLC-MS/MS assay was developed for screening purposes with a sample turnaround time of 2.7 minutes. The assay was consolidated such that only four dried blood spot punches were required, and it displayed good precision and reproducibility.

Conclusion: We report a highly multiplexed UPLC-MS/MS assay that is appropriate for the newborn screening of 15 lysosomal storage diseases and 3 additional inborn errors. It can be further expanded to include additional conditions for which presymptomatic diagnosis may facilitate optimum treatment outcome.

Keywords: UPLC-MS/MS; biomarker; enzymatic assay; multiplex; newborn screening.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromatography, Liquid
  • Dried Blood Spot Testing
  • Humans
  • Infant, Newborn
  • Lysosomal Storage Diseases* / diagnosis
  • Lysosomal Storage Diseases* / genetics
  • Lysosomes
  • Neonatal Screening*
  • Reproducibility of Results
  • Tandem Mass Spectrometry