{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:31:14Z","timestamp":1792805474513,"version":"4.5.0"},"reference-count":29,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UCL Biological Mass Spectrometry Centre","award":["NIHR203317"],"award-info":[{"award-number":["NIHR203317"]}],"id":[{"id":"https:\/\/ror.org\/00x1cgf82","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Great Ormond Street Biomedical Research Centre","award":["NIHR203317"],"award-info":[{"award-number":["NIHR203317"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013VI (n = 52), and Niemann\u2013Pick 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\u201397% 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.<\/jats:p>","DOI":"10.3390\/ijms241210177","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T01:31:31Z","timestamp":1686879091000},"page":"10177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases"],"prefix":"10.3390","volume":"24","author":[{"given":"Justyna","family":"Spiewak","sequence":"first","affiliation":[{"name":"Inborn Errors of Metabolism Section, Genetics & Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, University College London, London WC1 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Doykov","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism Section, Genetics & Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, University College London, London WC1 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolos","family":"Papandreou","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism Section, Genetics & Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, University College London, London WC1 1EH, UK"},{"name":"Molecular Neurosciences, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, University College London, London WC1 1EH, UK"},{"name":"Department of Neurology, Great Ormond Street Hospital for Children, London WC1N 3JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"H\u00e4llqvist","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism Section, Genetics & Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, University College London, London WC1 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa","family":"Mills","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism Section, Genetics & Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, University College London, London WC1 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7592-4302","authenticated-orcid":false,"given":"Peter T.","family":"Clayton","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism Section, Genetics & Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, University College London, London WC1 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9712-6122","authenticated-orcid":false,"given":"Paul","family":"Gissen","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism Section, Genetics & Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, University College London, London WC1 1EH, UK"},{"name":"Department of Metabolic Medicine, Great Ormond Street Hospital for Children, London WC1N 3JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0763-8288","authenticated-orcid":false,"given":"Kevin","family":"Mills","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism Section, Genetics & Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, University College London, London WC1 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy E.","family":"Heywood","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism Section, Genetics & Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, University College London, London WC1 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1111\/dmcn.15334","article-title":"Niemann-Pick type C disease as proof-of-concept for intelligent biomarker panel selection in neurometabolic disorders","volume":"64","author":"Papandreou","year":"2022","journal-title":"Dev. 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