Newborn screening for X-linked adrenoleukodystrophy (X-ALD): Validation of a combined liquid chromatography–tandem mass spectrometric (LC–MS/MS) method
Abstract
Newborn screening for X-linked adrenoleukodystrophy (X-ALD) has until now been limited in implementation because of the lack of an accepted standard methodology. We have previously reported a technique using LC-MS/MS analysis that could provide the basis for screening of newborns for X-ALD. The target analyte diagnostic for X-ALD and other peroxisomal disorders of peroxisomal beta-oxidation is 1-hexacosanoyl-2-lyso-sn-3-glycero-phosphorylcholine (26:0-lyso-PC). We report here the validation of the analytical method using an authentic standard of the target compound. The method possesses sensitivity of <1.0fmole injected on column with a correlation coefficient (R(2)) of 0.9987. A tetradeuterated analog of 26:0-lyso-PC served as the internal standard. The sensitivity of this clinical method was confirmed using 17 newborn samples of individuals with peroxisomal disorders retrieved from state newborn screening programs. These samples were run masked with over 1000 newborn samples. All affected individuals were identified with one exception. One sample which was retrieved as an affected did not have the biochemical or genetic abnormality of X-ALD and thus is considered an error in sample identity. These studies clearly show that the method is highly sensitive and accurate in identifying individuals with a defect in peroxisomal beta-oxidation such as X-ALD.
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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 [69]
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- Authors
- Hubbard, W. C., Moser, A. B., Liu, A. C., Jones, R. O., Steinberg, S. J., Lorey, F., Panny, S. R., Vogt Jr., R. F., Macaya, D., & Turgeon, C. T.
- Affiliations
- Johns Hopkins University (US)
- Kennedy Krieger Institute (US)
- California Department of Public Health (US)
- Maryland Department of Health (US)
- Mayo Clinic (US)
- Corresponding author
- Hubbard, Walter C.
- Venue
- Molecular Genetics and Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 97
- Issue
- 3
- Pages
- 212-220
- ISSN
- 1096-7192 (ISSN-L)
- OpenAlex
- W2154833816
- Cited by
- 177
- References
- 1
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 7 · 2023: 3 · 2022: 13 · 2021: 16 · 2020: 8 · 2019: 9 · 2018: 13 · 2017: 13 · 2016: 18 · 2015: 12 · 2014: 8 · 2013: 8 · 2012: 13
- FWCI
- 7.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Genetics and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- Association Européenne contre les Leucodystrophies
- National Institutes of Health (1s10rr016798-01)
- National Center for Research Resources (1 S10 RR16798)
- 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, newborn screening, peroxisomal disorders, peroxisomal beta-oxidation, LC-MS/MS method validation, diagnostic biomarkers, analytical sensitivity
- MeSH terms
- Adolescent, Adrenoleukodystrophy, Child, Child, Preschool, Chromatography, Liquid, Humans, Infant, Newborn, Lysophosphatidylcholines, Reference Standards, Neonatal Screening, Tandem Mass Spectrometry
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