Comparison of the Diagnostic Performance of C26:0-Lysophosphatidylcholine and Very Long-Chain Fatty Acids Analysis for Peroxisomal Disorders
Open accessAbstract
Peroxisomes are subcellular organelles that are involved in various important physiological processes such as the oxidation of fatty acids and the biosynthesis of bile acids and plasmalogens. The gold standard in the diagnostic work-up for patients with peroxisomal disorders is the analysis of very long-chain fatty acid (VLCFA) levels in plasma. Alternatively, C26:0-lysophosphatidylcholine (C26:0-LPC) can be measured in dried blood spots (DBS) using liquid chromatography tandem mass spectrometry (LC-MS/MS); a fast and easy method but not yet widely used. Currently, little is known about the correlation of C26:0-LPC in DBS and C26:0-LPC in plasma, and how C26:0-LPC analysis compares to VLCFA analysis in diagnostic performance. We investigated the correlation between C26:0-LPC levels measured in DBS and plasma prepared from the same blood sample. For this analysis we included 43 controls and 38 adrenoleukodystrophy (ALD) (21 males and 17 females) and 33 Zellweger spectrum disorder (ZSD) patients. In combined control and patient samples there was a strong positive correlation between DBS and plasma C26:0-LPC (Spearman’s rank correlation coefficient of r (114) = 0.962, p < 0.001). These data show that both plasma and DBS are suitable to determine blood C26:0-LPC levels and that there is a strong correlation between C26:0-LPC levels in both matrices. Following this, we investigated how VLCFA and C26:0-LPC analysis compare in diagnostic performance for 67 controls, 26 ALD males, 19 ALD females, and 35 ZSD patients. For C26:0-LPC, all ALD and ZSD samples had C26:0-LPC levels above the upper limit of the reference range. For C26:0, one out of 67 controls had C26:0 levels above the upper reference range. For 1 out of 26 (1/26) ALD males, 1/19 ALD females and 3/35 ZSD patients, the C26:0 concentration was within the reference range. The C26:0/C22:0 ratio was within the reference range for 0/26 ALD males, 1/19 ALD females and 2/35 ZSD patients. Overall, these data demonstrate that C26:0-LPC analysis has a superior diagnostic performance compared to VLCFA analysis (C26:0 and C26:0/C22:0 ratio) in all patient groups. Based on our results we recommend implementation of C26:0-LPC analysis in DBS and/or plasma in the diagnostic work-up 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 [18]
The Discussion (page not available) reports that plasma VLCFA analysis gives false negatives in approximately 15–20% of women with ALD, consistent with roughly 80–85% sensitivity. The Results report elevated C26:0-LPC in all 19 women with ALD studied, but that small cohort does not establish a general sensitivity greater than 99% in women. (LLM, conf=0.84)
Experimental — accuracy not yet measuredFor biochemical testing, plasma C26:0-lysophosphatidylcholine has superior diagnostic performance.
“For biochemical testing, plasma C26:0-lysophosphatidylcholine (C26:0-lysoPC) has superior diagnostic performance.18”
From International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy (2022) · cites this paper as [18]
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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-citationTreatment of cerebral adrenoleukodystrophy: allogeneic transplantation and lentiviral gene therapy
Gupta, A. O., Raymond, G., Pierpont, E. I., Kemp, S., McIvor, R. S., Rayannavar, A., Miller, B., Lund, T. C., & Orchard, P. J. (2022) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2022.2124857 · Cited by 67 · see citing works
“a sensitivity of >99% in diagnosing women with ALD, including those with normal plasma VLCFA levels [9].”
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- Authors
- Jaspers, Y. R. J., Ferdinandusse, S., Dijkstra, I. M. E., Barendsen, R. W., van Lenthe, H., Kulik, W., Engelen, M., Goorden, S. M. I., Vaz, F. M., & Kemp, S.
- Affiliations
- Amsterdam University Medical Centers (NL)
- Emma Kinderziekenhuis (NL)
- Corresponding author
- Kemp, Stephan
- ORCID
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2020-07-29
- Volume
- 8
- Pages
- 690-690
- ISSN
- 2296-634X (ISSN-L)
- PMC
- PMC7438929
- OpenAlex
- W3043111269
- Cited by
- 69
- References
- 6
- Citations by year
- 2026: 15 · 2025: 11 · 2024: 13 · 2023: 12 · 2022: 9 · 2021: 9
- FWCI
- 4.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Funders
- ZonMw (543002004)
- 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
- very long chain fatty acids, peroxisomal disorders, adrenoleukodystrophy, Zellweger spectrum disorder, dried blood spots, plasma biomarkers, diagnostic performance, peroxisome biogenesis disorders, diagnostic accuracy, LC-MS/MS quantification
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