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New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases

Authors :
Heywood, Justyna Spiewak
Ivan Doykov
Apostolos Papandreou
Jenny Hällqvist
Philippa Mills
Peter T. Clayton
Paul Gissen
Kevin Mills
Wendy E.
Source :
International Journal of Molecular Sciences; Volume 24; Issue 12; Pages: 10177
Publication Year :
2023
Publisher :
Multidisciplinary Digital Publishing Institute, 2023.

Abstract

Dried blood spots (DBSs) biomarkers are convenient for monitoring for specific lysosomal storage diseases (LSDs), but they could have relevance for other LSDs. To determine the specificity and utility of glycosphingolipidoses biomarkers against other LSDs, we applied a multiplexed lipid liquid chromatography tandem mass spectrometry assay to a DBS cohort of healthy controls (n = 10) and Gaucher (n = 4), Fabry (n = 10), Pompe (n = 2), mucopolysaccharidosis types I–VI (n = 52), and Niemann–Pick disease type C (NPC) (n = 5) patients. We observed no complete disease specificity for any of the markers tested. However, comparison among the different LSDs highlighted new applications and perspectives of the existing biomarkers. We observed elevations in glucosylceramide isoforms in the NPC and Gaucher patients relative to the controls. In NPC, there was a greater proportion of C24 isoforms, giving a specificity of 96–97% for NPC, higher than 92% for the NPC biomarker N-palmitoyl-O-phosphocholineserine ratio to lyso-sphingomyelin. We also observed significantly elevated levels of lyso-dihexosylceramide in Gaucher and Fabry disease as well as elevated lyso-globotriaosylceramide (Lyso-Gb3) in Gaucher disease and the neuronopathic forms of Mucopolysaccharidoses. In conclusion, DBS glucosylceramide isoform profiling has increased the specificity for the detection of NPC, thereby improving diagnostic accuracy. Low levels of lyso-lipids can be observed in other LSDs, which may have implications in their disease pathogenesis.

Details

Language :
English
ISSN :
14220067
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences; Volume 24; Issue 12; Pages: 10177
Accession number :
edsair.multidiscipl..83df7b1e7fdc10f67b191b0104f8406b
Full Text :
https://doi.org/10.3390/ijms241210177