Detection of GM1-gangliosidosis in newborn dried blood spots by enzyme activity and biomarker assays using tandem mass spectrometry

J Inherit Metab Dis. 2021 Jan;44(1):264-271. doi: 10.1002/jimd.12269. Epub 2020 Aug 26.

Abstract

GM1-gangliosidosis is a rare autosomal recessive lysosomal storage disease caused by deficiency of β-galactosidase (GLB1). Newborn screening (NBS) may be warranted in the near future given the initiation of a number of gene therapy clinical trials. Here, we report a tandem mass spectrometry (MS/MS) enzymatic assay of GLB1 using dried blood spots (DBS), and the demonstration that GLB1 activities in newborn DBS from seven GM1-gangliosidosis patients are well below those measured in random newborn DBS. MS/MS analysis of two glycan biomarkers, dp5 and A2G2, shows high elevation in newborn DBS from GM1-gangliosidosis compared to the levels in the nonaffected reference range.

Keywords: GM1-gangliosidosis; beta-Galactosidase; biomarkers; dried blood spots; newborn screening; tandem mass spectrometry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Case-Control Studies
  • Dried Blood Spot Testing / methods
  • Gangliosidosis, GM1 / blood
  • Gangliosidosis, GM1 / diagnosis*
  • Humans
  • Infant, Newborn
  • Neonatal Screening / methods
  • Tandem Mass Spectrometry
  • beta-Galactosidase / physiology*

Substances

  • Biomarkers
  • GLB1 protein, human
  • beta-Galactosidase