Comparison of C26:0-carnitine and C26:0-lysophosphatidylcholine as diagnostic markers in dried blood spots from newborns and patients with adrenoleukodystrophy
Abstract
X-linked adrenoleukodystrophy (ALD) is the most common leukodystrophy with a birth incidence of 1:14,700 live births. The disease is caused by mutations in ABCD1 and characterized by very long-chain fatty acids (VLCFA) accumulation. In childhood, male patients are at high-risk to develop adrenal insufficiency and/or cerebral demyelination. Timely diagnosis is essential. Untreated adrenal insufficiency can be life-threatening and hematopoietic stem cell transplantation is curative for cerebral ALD provided the procedure is performed in an early stage of the disease. For this reason, ALD is being added to an increasing number of newborn screening programs. ALD newborn screening involves the quantification of C26:0-lysoPC in dried blood spots which requires a dedicated method. C26:0-carnitine, that was recently identified as a potential new biomarker for ALD, has the advantage that it can be added as one more analyte to the routine analysis of amino acids and acylcarnitines already in use. The first objective of this study was a comparison of the sensitivity of C26:0-carnitine and C26:0-lysoPC in dried blood spots from control and ALD newborns both in a case-control study and in newborns included in the New York State screening program. While C26:0-lysoPC was elevated in all ALD newborns, C26:0-carnitine was elevated only in 83%. Therefore, C26:0-carnitine is not a suitable biomarker to use in ALD newborn screen. In women with ALD, plasma VLCFA analysis results in a false negative result in approximately 15-20% of cases. The second objective of this study was to compare plasma VLCFA analysis with C26:0-carnitine and C26:0-lysoPC in dried blood spots of women with ALD. Our results show that C26:0-lysoPC was elevated in dried blood spots from all women with ALD, including from those with normal plasma C26:0 levels. This shows that C26:0-lysoPC is a better and more accurate biomarker for ALD than plasma VLCFA levels. We recommend that C26:0-lysoPC be added to the routine biochemical array of diagnostic tests for peroxisomal disorders.
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In women, the sensitivity of VLCFA analysis is 85%, whereas C26:0-lysoPC has a sensitivity of greater than 99%.
“In women, the sensitivity of VLCFAs analysis is 85%, whereas C26:0-lysoPC has a sensitivity of >99%.18,19,22”
From International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy (2022) · cites this paper as [19]
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International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy
Engelen, M., van Ballegoij, W. J. C., Mallack, E. J., Van Haren, K. P., Köhler, W., Salsano, E., van Trotsenburg, A. S. P., Mochel, F., Sevin, C., Regelmann, M. O., et al. (2022) · Neurology · doi:10.1212/wnl.0000000000201374 · Cited by 156 · see citing works
Self-citation
- Authors
- Huffnagel, I. C., van de Beek, M.-C., Showers, A. L., Orsini, J. J., Klouwer, F. C. C., Dijkstra, I. M. E., Schielen, P. C., van Lenthe, H., Wanders, R. J. A., Vaz, F. M., Morrissey, M. A., Engelen, M., & Kemp, S.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- New York State Department of Health (US)
- National Institute for Public Health and the Environment (NL)
- Corresponding author
- Kemp, Stephan
- ORCID
- Venue
- Molecular Genetics and Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 122
- Issue
- 4
- Pages
- 209-215
- ISSN
- 1096-7192 (ISSN-L)
- OpenAlex
- W2765456519
- Cited by
- 71
- References
- 42
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 10 · 2023: 6 · 2022: 5 · 2021: 14 · 2020: 14 · 2019: 9 · 2018: 2
- FWCI
- 4.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Genetics and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Rivm Repository (Netherlands National Institute for Public Health and the Environment) (submittedVersion)
- Funders
- European Leukodystrophy Association (2015-015I1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
- Keywords
- X-linked adrenoleukodystrophy, dried blood spots, newborn screening, biomarkers, very long chain fatty acids, ABCD1 mutations, diagnostic sensitivity, adrenal insufficiency, brain demyelination
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily D, Member 1, Adrenoleukodystrophy, Adult, Carnitine, Fatty Acids, Female, Humans, Infant, Newborn, Lysophosphatidylcholines, Male, Netherlands, New York, Sensitivity and Specificity, Cohort Studies, Biomarkers, Neonatal Screening, Case-Control Studies, Dried Blood Spot Testing
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