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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10299042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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