C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man
X-linked adrenoleukodystrophy (ALD), a progressive neurodegenerative disease, is caused by mutations in ABCD1 and characterized by very-long-chain fatty acids (VLCFA) accumulation. Virtually all males develop progressive myelopathy (AMN). A subset of patients, however, develops a fatal cerebral demy...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849772/ |
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pubmed-4849772 |
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pubmed-48497722016-05-07 C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man van de Beek, Malu-Clair Dijkstra, Inge M. E. van Lenthe, Henk Ofman, Rob Goldhaber-Pasillas, Dalia Schauer, Nicolas Schackmann, Martin Engelen-Lee, Joo-Yeon Vaz, Frédéric M. Kulik, Wim Wanders, Ronald J. A. Engelen, Marc Kemp, Stephan Research Article X-linked adrenoleukodystrophy (ALD), a progressive neurodegenerative disease, is caused by mutations in ABCD1 and characterized by very-long-chain fatty acids (VLCFA) accumulation. Virtually all males develop progressive myelopathy (AMN). A subset of patients, however, develops a fatal cerebral demyelinating disease (cerebral ALD). Hematopoietic stem cell transplantation is curative for cerebral ALD provided the procedure is performed in an early stage of the disease. Unfortunately, this narrow therapeutic window is often missed. Therefore, an increasing number of newborn screening programs are including ALD. To identify new biomarkers for ALD, we developed an Abcd1 knockout mouse with enhanced VLCFA synthesis either ubiquitous or restricted to oligodendrocytes. Biochemical analysis revealed VLCFA accumulation in different lipid classes and acylcarnitines. Both C26:0-lysoPC and C26:0-carnitine were highly elevated in brain, spinal cord, but also in bloodspots. We extended the analysis to patients and confirmed that C26:0-carnitine is also elevated in bloodspots from ALD patients. We anticipate that validation of C26:0-carnitine for the diagnosis of ALD in newborn bloodspots may lead to a faster inclusion of ALD in newborn screening programs in countries that already screen for other inborn errors of metabolism. Public Library of Science 2016-04-28 /pmc/articles/PMC4849772/ /pubmed/27124591 http://dx.doi.org/10.1371/journal.pone.0154597 Text en © 2016 van de Beek et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
van de Beek, Malu-Clair Dijkstra, Inge M. E. van Lenthe, Henk Ofman, Rob Goldhaber-Pasillas, Dalia Schauer, Nicolas Schackmann, Martin Engelen-Lee, Joo-Yeon Vaz, Frédéric M. Kulik, Wim Wanders, Ronald J. A. Engelen, Marc Kemp, Stephan |
| spellingShingle |
van de Beek, Malu-Clair Dijkstra, Inge M. E. van Lenthe, Henk Ofman, Rob Goldhaber-Pasillas, Dalia Schauer, Nicolas Schackmann, Martin Engelen-Lee, Joo-Yeon Vaz, Frédéric M. Kulik, Wim Wanders, Ronald J. A. Engelen, Marc Kemp, Stephan C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man |
| author_facet |
van de Beek, Malu-Clair Dijkstra, Inge M. E. van Lenthe, Henk Ofman, Rob Goldhaber-Pasillas, Dalia Schauer, Nicolas Schackmann, Martin Engelen-Lee, Joo-Yeon Vaz, Frédéric M. Kulik, Wim Wanders, Ronald J. A. Engelen, Marc Kemp, Stephan |
| author_sort |
van de Beek, Malu-Clair |
| title |
C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man |
| title_short |
C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man |
| title_full |
C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man |
| title_fullStr |
C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man |
| title_full_unstemmed |
C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man |
| title_sort |
c26:0-carnitine is a new biomarker for x-linked adrenoleukodystrophy in mice and man |
| description |
X-linked adrenoleukodystrophy (ALD), a progressive neurodegenerative disease, is caused by mutations in ABCD1 and characterized by very-long-chain fatty acids (VLCFA) accumulation. Virtually all males develop progressive myelopathy (AMN). A subset of patients, however, develops a fatal cerebral demyelinating disease (cerebral ALD). Hematopoietic stem cell transplantation is curative for cerebral ALD provided the procedure is performed in an early stage of the disease. Unfortunately, this narrow therapeutic window is often missed. Therefore, an increasing number of newborn screening programs are including ALD. To identify new biomarkers for ALD, we developed an Abcd1 knockout mouse with enhanced VLCFA synthesis either ubiquitous or restricted to oligodendrocytes. Biochemical analysis revealed VLCFA accumulation in different lipid classes and acylcarnitines. Both C26:0-lysoPC and C26:0-carnitine were highly elevated in brain, spinal cord, but also in bloodspots. We extended the analysis to patients and confirmed that C26:0-carnitine is also elevated in bloodspots from ALD patients. We anticipate that validation of C26:0-carnitine for the diagnosis of ALD in newborn bloodspots may lead to a faster inclusion of ALD in newborn screening programs in countries that already screen for other inborn errors of metabolism. |
| publisher |
Public Library of Science |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849772/ |
| _version_ |
1613572908090654720 |