Newborn screening for X-linked adrenoleukodystrophy: Further evidence high throughput screening is feasible
Open accessAbstract
X-linked adrenoleukodystrophy (ALD) is characterized by adrenal insufficiency and neurologic involvement with onset at variable ages. Plasma very long chain fatty acids are elevated in ALD; even in asymptomatic patients. We demonstrated previously that liquid chromatography tandem mass spectrometry measuring C26:0 lysophosphatidylcholine reliably identifies affected males. We prospectively applied this method to 4689 newborn blood spot samples; no false positives were observed. We show that high throughput neonatal screening for ALD is methodologically feasible.
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The feasibility of C26:0-LPC determination has been proven by two large pilot studies based on either liquid chromatography MS/MS or flow injection analysis MS/MS.
“The feasibility of C26:0-LPC determination has been proven by two large pilot studies based on either liquid chromatography MS/MS72 or flow injection analysis MS/MS.73”
From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [72]
Citation 73 is attached specifically to the flow-injection MS/MS pilot study. The cited paper’s Methods (§2.2) instead describe chromatography using a UPLC column before MS/MS, and its Results (§3) report analysis of 4,689 newborn samples by that LC-MS/MS method. It supports the feasibility of screening, but not the flow-injection method attributed to it. (LLM, conf=0.88)
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Experimental — accuracy not yet measuredDetermination of C26:0-LPC will also identify the majority of female X-ALD carriers as well as patients affected by different peroxisomal biogenesis disorders or single enzyme deficiencies of the peroxisomal beta-oxidation pathway.
“In addition to the detection of male X-ALD patients, determination of C26:0-LPC will also identify the majority of female X-ALD carriers as well as patients affected by different peroxisomal biogenesis disorders or single enzyme deficiencies of the peroxisomal beta-oxidation pathway.72,74”
From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [72]
The Discussion (page unavailable) says screening may identify female heterozygotes and that positive results can reflect peroxisomal biogenesis disorders. It expects only a portion of female heterozygotes to be identified, however, not necessarily a majority. The Introduction mentions single-enzyme defects but does not establish that this test identifies patients with them. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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References 20 · Cited by 56
Research works printed but not linked: 14
- [3]Polgreen LE Chahla S Miller W Rothman S Tolar J Kivisto T Early diagnosis of cerebral X-linked adrenoleukodystrophy in boys with Addison's disease improves survival and neurological outcomes Eur J Pediatr 170 8 2011 1049 1054 21279382 PMC3101278
- [4]Stephenson DJ Bezman L Raymond GV Acute presentation of childhood adrenoleukodystrophy Neuropediatrics 31 6 2000 293 297 11508547
- [5]Ravid S Diamond AS Eviatar L Coma as an acute presentation of adrenoleukodystrophy Pediatr Neurol 22 3 2000 237 239 10734258
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- [7]Morell BK Teichler J Budak K Vollenweider J Pavlicek V X-linked adrenoleukodystrophy presenting as Addison's disease BMJ Case Rep 2010 2010. pii: bcr1120092419 10.1136/bcr.11.2009.2419.:bcr1120092419 PMC3047513 22753300 · DOI
- [8]Moser AB Kreiter N Bezman L Lu S Raymond GV Naidu S Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls Ann Neurol 45 1 1999 100 110 9894883
- [9]Miller WP Rothman SM Nascene D Kivisto T DeFor TE Ziegler RS Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report Blood 118 7 2011 1971 1978 21586746
- [10]Cartier N Aubourg P Hematopoietic stem cell transplantation and hematopoietic stem cell gene therapy in X-linked adrenoleukodystrophy Brain Pathol 20 4 2010 857 862 20626747 PMC8094635
- [11]Maccotta L Sherr EH Hematopoietic stem cell transplantation for the treatment of childhood cerebral X-linked adrenoleukodystrophy Nat Clin Pract Neurol 4 3 2008 130 131 18212787
- [12]Peters C Charnas LR Tan Y Ziegler RS Shapiro EG DeFor T Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999 Blood 104 3 2004 881 888 15073029
- [13]Mahmood A Raymond GV Dubey P Peters C Moser HW Survival analysis of haematopoietic cell transplantation for childhood cerebral X-linked adrenoleukodystrophy: a comparison study Lancet Neurol 6 8 2007 687 692 17618834
- [15]Wang Y Busin R Reeves C Bezman L Raymond G Toomer CJ X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism Mol Genet Metab 104 1-2 2011 160 166 21700483
- [18]Hubbard WC Moser AB Liu AC Jones RO Steinberg SJ Lorey F Newborn screening for X-linked adrenoleukodystrophy (X-ALD): validation of a combined liquid chromatography-tandem mass spectrometric (LC-MS/MS) method Mol Genet Metab 97 3 2009 212 220 19423374
- [19]Moser HW Therapy of X-linked adrenoleukodystrophy NeuroRx 3 2 2006 246 253 16554262 PMC3593437
- Authors
- Theda, C., Gibbons, K., DeFor, T. E., Donohue, P. K., Golden, W. C., Kline, A. D., Gulamali-Majid, F., Panny, S. R., Hubbard, W. C., Jones, R. O., Liu, A. K., Moser, A. B., & Raymond, G. V.
- Affiliations
- Royal Women's Hospital (AU)
- Kennedy Krieger Institute (US)
- University of Minnesota (US)
- Johns Hopkins University (US)
- Greater Baltimore Medical Center (US)
- Maryland Department of Health (US)
- Corresponding author
- Theda, Christiane
- ORCID
- Venue
- Molecular Genetics and Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 111
- Issue
- 1
- Pages
- 55-57
- ISSN
- 1096-7192 (ISSN-L)
- PMC
- PMC3935823
- OpenAlex
- W2027379705
- Cited by
- 56
- References
- 20
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 7 · 2021: 1 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 6 · 2016: 9 · 2015: 8 · 2014: 4
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Genetics and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Association Européenne contre les Leucodystrophies
- National Institutes of Health (UL1TR000114, 1s10rr016798-01, UL1TR001079)
- National Cancer Institute (P30CA077598)
- National Center for Research Resources (1 S10 RR16798)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD057136)
- 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 › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- X-linked adrenoleukodystrophy, newborn screening, high-throughput screening, very long chain fatty acids, lysophosphatidylcholine, plasma biomarkers, liquid chromatography-tandem mass spectrometry, adrenal insufficiency, screening feasibility
- MeSH terms
- Adrenoleukodystrophy, Chromatography, Liquid, Female, Humans, Infant, Newborn, Lysophosphatidylcholines, Male, Prospective Studies, Neonatal Screening, Tandem Mass Spectrometry
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