C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man
Open accessAbstract
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.
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OL peroxisomes are largely responsible for VLCFA synthesis and degradation in the adult brain.
“OL peroxisomes are largely responsible for VLCFA synthesis [204] and degradation [166] in the adult brain.”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [204]
In Results and Discussion, under “Targeting ELOVL1 Expression to Oligodendrocytes” (page not specified), the paper concludes that oligodendrocytes are largely responsible for brain VLCFA synthesis and degradation. But this source is cited for the synthesis portion of the sentence, and it does not attribute that synthesis specifically to oligodendrocyte peroxisomes; its ELOVL1 results place the synthesis enzyme at the endoplasmic reticulum. (LLM, conf=0.87)
Experimental — accuracy not yet measuredBrain OLs account for the majority of VLCFA synthesis by using their ELOVL1.
“Brain OLs account for the majority of VLCFA synthesis [166,204] by using their ELOVL1 [205,206,207,208].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [204]
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Cites
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Self-citation
- Authors
- van de Beek, M.-C., Dijkstra, I. M. E., van Lenthe, H., Ofman, R., Goldhaber-Pasillas, D., Schauer, N., Schackmann, M., Engelen-Lee, J.-Y., Vaz, F. M., Kulik, W., Wanders, R. J. A., Engelen, M., & Kemp, S.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Kemp, Stephan
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-04-28
- Volume
- 11
- Issue
- 4
- Pages
- e0154597
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4849772
- OpenAlex
- W2342942063
- Cited by
- 48
- References
- 14
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 7 · 2016: 2
- FWCI
- 5.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (acceptedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- European Leukodystrophy Association (ELA:2006-031I4, ELA:2007-026I4, ELA:2011-024I1, ELA:2014-014I1)
- European Union Framework Programme 7 (LeukoTreat (241622))
- Marie Curie International Training Network (PerFuMe (316723))
- Netherlands Organization for Scientific Research (VIDI-grant 91786328)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- X-linked adrenoleukodystrophy, biomarkers, ABCD1, very long chain fatty acids, acylcarnitines, lysophosphatidylcholine, oligodendrocytes, newborn screening, hematopoietic stem cell transplantation, cerebral adrenoleukodystrophy, inborn errors of metabolism
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily D, Member 1, Fatty Acid Elongases, Acetyltransferases, Adrenoleukodystrophy, Animals, Brain, Carnitine, Fatty Acids, Humans, Lysophosphatidylcholines, Male, Mice, Inbred C57BL, Oligodendroglia, Spinal Cord, Biomarkers, Mice, Knockout, ATP-Binding Cassette Transporters, Early Diagnosis, Mice, Gene Knock-In Techniques
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