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C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease
Farber disease (FD) is a rare autosomal recessive disease caused by mutations in the acid ceramidase gene (ASAH1). Low ceramidase activity results in the accumulation of fatty substances, mainly ceramides. Hallmark symptoms at clinical level are periarticular nodules, lipogranulomas, swollen and pai...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522391/ https://www.ncbi.nlm.nih.gov/pubmed/28733637 http://dx.doi.org/10.1038/s41598-017-06604-2 |
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author | Cozma, Claudia Iurașcu, Marius-Ionuț Eichler, Sabrina Hovakimyan, Marina Brandau, Oliver Zielke, Susanne Böttcher, Tobias Giese, Anne-Katrin Lukas, Jan Rolfs, Arndt |
author_facet | Cozma, Claudia Iurașcu, Marius-Ionuț Eichler, Sabrina Hovakimyan, Marina Brandau, Oliver Zielke, Susanne Böttcher, Tobias Giese, Anne-Katrin Lukas, Jan Rolfs, Arndt |
author_sort | Cozma, Claudia |
collection | PubMed |
description | Farber disease (FD) is a rare autosomal recessive disease caused by mutations in the acid ceramidase gene (ASAH1). Low ceramidase activity results in the accumulation of fatty substances, mainly ceramides. Hallmark symptoms at clinical level are periarticular nodules, lipogranulomas, swollen and painful joints and a hoarse voice. FD phenotypes are heterogeneous varying from mild to very severe cases, with the patients not surviving past their first year of life. The diagnostic aspects of FD are poorly developed due to the rarity of the disease. In the present study, the screening for ceramides and related molecules was performed in Farber affected patients (n = 10), carriers (n = 11) and control individuals (n = 192). This study has the highest number of enrolled Farber patients and carriers reported to present. Liquid chromatography multiple reaction mass spectrometry (LC/MRM-MS) studies revealed that the ceramide C26:0 and especially its isoform 1 is a highly sensitive and specific biomarker for FD (p < 0.0001). The new biomarker can be determined directly in the dried blood spot extracts with low sample consumption. This allows for easy sample preparation, high reproducibility and use in high throughput screenings. |
format | Online Article Text |
id | pubmed-5522391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55223912017-07-26 C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease Cozma, Claudia Iurașcu, Marius-Ionuț Eichler, Sabrina Hovakimyan, Marina Brandau, Oliver Zielke, Susanne Böttcher, Tobias Giese, Anne-Katrin Lukas, Jan Rolfs, Arndt Sci Rep Article Farber disease (FD) is a rare autosomal recessive disease caused by mutations in the acid ceramidase gene (ASAH1). Low ceramidase activity results in the accumulation of fatty substances, mainly ceramides. Hallmark symptoms at clinical level are periarticular nodules, lipogranulomas, swollen and painful joints and a hoarse voice. FD phenotypes are heterogeneous varying from mild to very severe cases, with the patients not surviving past their first year of life. The diagnostic aspects of FD are poorly developed due to the rarity of the disease. In the present study, the screening for ceramides and related molecules was performed in Farber affected patients (n = 10), carriers (n = 11) and control individuals (n = 192). This study has the highest number of enrolled Farber patients and carriers reported to present. Liquid chromatography multiple reaction mass spectrometry (LC/MRM-MS) studies revealed that the ceramide C26:0 and especially its isoform 1 is a highly sensitive and specific biomarker for FD (p < 0.0001). The new biomarker can be determined directly in the dried blood spot extracts with low sample consumption. This allows for easy sample preparation, high reproducibility and use in high throughput screenings. Nature Publishing Group UK 2017-07-21 /pmc/articles/PMC5522391/ /pubmed/28733637 http://dx.doi.org/10.1038/s41598-017-06604-2 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Cozma, Claudia Iurașcu, Marius-Ionuț Eichler, Sabrina Hovakimyan, Marina Brandau, Oliver Zielke, Susanne Böttcher, Tobias Giese, Anne-Katrin Lukas, Jan Rolfs, Arndt C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease |
title | C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease |
title_full | C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease |
title_fullStr | C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease |
title_full_unstemmed | C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease |
title_short | C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease |
title_sort | c26-ceramide as highly sensitive biomarker for the diagnosis of farber disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522391/ https://www.ncbi.nlm.nih.gov/pubmed/28733637 http://dx.doi.org/10.1038/s41598-017-06604-2 |
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