Detection of <scp>GM1‐gangliosidosis</scp> in newborn dried blood spots by enzyme activity and biomarker assays using tandem mass spectrometry
Peiling Su, Hamid Khaledi, Christine Waggoner, Michael H. Gelb
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.
Topics & Concepts
GangliosidosisNewborn screeningDried bloodTandem mass spectrometryLysosomal storage diseaseBiomarkerGlycanReference rangeEnzymeMass spectrometryChemistryMedicineChromatographyBiochemistryInternal medicineGlycoproteinLysosomal Storage Disorders ResearchErythrocyte Function and PathophysiologyCellular transport and secretion