Improved analysis of C26:0-lysophosphatidylcholine in dried-blood spots via negative ion mode HPLC-ESI-MS/MS for X-linked adrenoleukodystrophy newborn screening
Abstract
Background X-linked adrenoleukodystrophy (X-ALD) is the most common human peroxisomal disorder, and is caused by mutations in the peroxisomal transmembrane ALD protein (ALDP, ABCD1). The biochemical defect associated with X-ALD is an accumulation of very long-chain fatty acids (VLCFA, e.g. C24:0 and C26:0), which has been shown to result in the accumulation of C26:0-lysophosphatidylcholine (C26:0-LPC). Methods We describe the analysis of C26:0-LPC in dried-blood spots (DBS) using a rapid (30 min) and simple extraction procedure, isocratic HPLC resolution of LPC, and structure-specific analysis via negative ion mode tandem mass spectrometry. Results In putative normal DBS specimens from newborns (N=223) C26:0-LPC was 0.09±0.03 μmol/l whole blood, while in peroxisomal biogenesis disorder (including X-ALD) patients (N=28) C26:0-LPC was 1.13±0.67 μmol/l whole blood. Both multiple reaction monitoring and a neutral loss scan (225.1 Da) analysis of DBS were used to analyze LPC. Conclusions Compared to a previous report of C26:0-LPC analysis in DBS, the method described here is simpler, faster, and more structure-specific for LPC with C26:0 acyl chains.
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Determination of C26:0 lysophosphatidylcholine (C26:0-LPC) from dried blood spots has turned out to be most promising for high-throughput biochemical screening for X-ALD and other metabolic disorders.
“Determination of C26:0 lysophosphatidylcholine (C26:0-LPC) from dried blood spots has turned out to be most promising and slightly different methods based on tandem mass spectrometry (MS/MS) were reported by different laboratories.68–71”
From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [71]
Cites
Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy
Cartier, N., Hacein-Bey-Abina, S., Bartholomae, C. C., Veres, G., Schmidt, M., Kutschera, I., Vidaud, M., Abel, U., Dal-Cortivo, L., Caccavelli, L., et al. (2009) · Science · doi:10.1126/science.1171242 · Cited by 1,508 · see citing works
Kemp, S., Pujol, A., Waterham, H. R., van Geel, B. M., Boehm, C. D., Raymond, G. V., Cutting, G. R., Wanders, R. J. A., & Moser, H. W. (2001) · Human Mutation · doi:10.1002/humu.1227 · Cited by 332 · see citing works
Adrenoleukodystrophy: Incidence, new mutation rate, and results of extended family screening
Bezman, L., Moser, A. B., Raymond, G. V., Rinaldo, P., Watkins, P. A., Smith, K. D., Kass, N. E., & Moser, H. W. (2001) · Annals of Neurology · doi:10.1002/ana.101 · Cited by 324 · see citing works
Pujol, A. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.5.499 · Cited by 214 · see citing works
Differential substrate specificities of human ABCD1 and ABCD2 in peroxisomal fatty acid β-oxidation
van Roermund, C. W. T., Visser, W. F., IJlst, L., Waterham, H. R., & Wanders, R. J. A. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.11.010 · Cited by 128 · see citing works
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Berger, J., Wiesinger, C., & Eichler, F. (2015) · The Application of Clinical Genetics · doi:10.2147/tacg.s49590 · Cited by 140 · see citing works
- Authors
- Haynes, C. A., & De Jesús, V. R.
- Affiliations
- Centers for Disease Control and Prevention (US)
- Corresponding author
- Haynes, Christopher A.
- Venue
- Clinica Chimica Acta
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 413
- Issue
- 15-16
- Pages
- 1217-1221
- ISSN
- 0009-8981 (ISSN-L)
- OpenAlex
- W2043030037
- Cited by
- 46
- References
- 5
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 6 · 2014: 4 · 2013: 3 · 2012: 1
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinica Chimica Acta (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Oak Ridge Institute for Science and Education
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- X-linked adrenoleukodystrophy, dried blood spots, newborn screening, peroxisomal disorders, very long chain fatty acids, ABCD1, peroxisome biogenesis disorders, neutral loss scan, multiple reaction monitoring
- MeSH terms
- Adrenoleukodystrophy, Chromatography, High Pressure Liquid, Humans, Infant, Newborn, Lysophosphatidylcholines, Reference Values, Neonatal Screening, Peroxisomal Disorders, Spectrometry, Mass, Electrospray Ionization, Tandem Mass Spectrometry, Dried Blood Spot Testing
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