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New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases

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 chrom...

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Autores principales: Spiewak, Justyna, Doykov, Ivan, Papandreou, Apostolos, Hällqvist, Jenny, Mills, Philippa, Clayton, Peter T., Gissen, Paul, Mills, Kevin, Heywood, Wendy E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299042/
https://www.ncbi.nlm.nih.gov/pubmed/37373322
http://dx.doi.org/10.3390/ijms241210177
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author Spiewak, Justyna
Doykov, Ivan
Papandreou, Apostolos
Hällqvist, Jenny
Mills, Philippa
Clayton, Peter T.
Gissen, Paul
Mills, Kevin
Heywood, Wendy E.
author_facet Spiewak, Justyna
Doykov, Ivan
Papandreou, Apostolos
Hällqvist, Jenny
Mills, Philippa
Clayton, Peter T.
Gissen, Paul
Mills, Kevin
Heywood, Wendy E.
author_sort Spiewak, Justyna
collection PubMed
description 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.
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spelling pubmed-102990422023-06-28 New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases Spiewak, Justyna Doykov, Ivan Papandreou, Apostolos Hällqvist, Jenny Mills, Philippa Clayton, Peter T. Gissen, Paul Mills, Kevin Heywood, Wendy E. Int J Mol Sci Article 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. MDPI 2023-06-15 /pmc/articles/PMC10299042/ /pubmed/37373322 http://dx.doi.org/10.3390/ijms241210177 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Spiewak, Justyna
Doykov, Ivan
Papandreou, Apostolos
Hällqvist, Jenny
Mills, Philippa
Clayton, Peter T.
Gissen, Paul
Mills, Kevin
Heywood, Wendy E.
New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases
title New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases
title_full New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases
title_fullStr New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases
title_full_unstemmed New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases
title_short New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases
title_sort new perspectives in dried blood spot biomarkers for lysosomal storage diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299042/
https://www.ncbi.nlm.nih.gov/pubmed/37373322
http://dx.doi.org/10.3390/ijms241210177
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