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Cited by 106Metabolism and Genetic DisordersLysosomal Storage Disorders ResearchAdrenal Hormones and Disorders

Newborn Screening for X-Linked Adrenoleukodystrophy

Open access
Moser, Ann, Jones, Richard, Hubbard, Walter, Tortorelli, Silvia, Orsini, Joseph, Caggana, Michele, Vogel, Beth, Raymond, Gerald·2016·International Journal of Neonatal Screening
DOI 10.3390/ijns2040015PMC PMC6715319
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Abstract

Early diagnosis of males with X-linked adrenoleukodystrophy (X-ALD) is essential for preventing loss of life due to adrenal insufficiency and for timely therapy of the childhood cerebral form of X-ALD with hematopoietic cell transplantation. This article describes X-ALD, the current therapies, the history of the development of the newborn screening test, the approval by the Secretary of Health and Human Services for the addition of X-ALD newborn screening to the recommended uniform panel of disorders screened as newborns (RUSP) and the successful implementation of X-ALD newborn screening in the state of New York beginning on 30 December 2013. Follow-up guidelines that have been established in New York are outlined. Based on the success of newborn screening in New York, and early results in Connecticut, where X-ALD newborn screening started in December 2015, and in California, where X-ALD newborn screening began in September 2016, we are confident and hopeful that X-ALD newborn screening will expand to include all US states and to countries that have established neonatal screening programs. The Minster of Health in the Netherlands has approved the addition of X-ALD to the newborn screening program with a start date expected in 2017. The states, such as Massachusetts, Illinois, Minnesota, New Jersey, Florida and Washington, that have legislative approval will commence screening as soon as budgetary resources, testing and follow-up procedures are in place.

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Crossref · 10.3390/ijns2040015

Cites

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  • Based on neonatal screening in the USA since 2013, the annual incidence of X-ALD is approximately 1/10,000, much higher than previously thought.

    “Based on neonatal screening in the USA since 2013, the annual incidence was found to be ~1/10,000 [2,7], much higher than previously thought [15].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [2]

    The New York screening section says screening began on 30 December 2013, but the Discussion reports a birth incidence of one in 14,700—not approximately one in 10,000. It also describes that rate as close to the earlier estimate of one in 17,000. In the citing sentence, the separate claim that incidence was 'much higher than previously thought' is attached to [15], not to this source. (LLM, conf=0.88)

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  • Early-stage treatment of childhood cerebral ALD with hematopoietic stem cell transplantation and, more recently, gene therapy can arrest disease progression if performed in the window of opportunity when the MRI is abnormal but neurological symptoms are not yet apparent.

    “Early-stage treatment of childhood cerebral ALD with hematopoietic stem cell transplantation and, more recently, gene therapy can arrest disease progression if performed in the window of opportunity when the MRI is abnormal but neurological symptoms are not yet apparent [7,38,43,44,45,46,47,48,49,50].”

    From Structure and Function of the ABCD1 Variant Database: 20 Years, 940 Pathogenic Variants, and 3400 Cases of Adrenoleukodystrophy (2022) · cites this paper as [7]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • The implementation of newborn screening for ALD in the United States and the Netherlands has provided the opportunity to identify patients at birth.

    “The implementation of newborn screening for ALD in the United States and the Netherlands has provided the opportunity to identify patients at birth [7,51,52,53,54,55,56].”

    From Structure and Function of the ABCD1 Variant Database: 20 Years, 940 Pathogenic Variants, and 3400 Cases of Adrenoleukodystrophy (2022) · cites this paper as [7]

    The Discussion reports that X-ALD newborn screening had been implemented in New York, Connecticut, and California, enabling identification of affected newborns. The Abstract says the Netherlands had approved screening but expected it to start in 2017; it does not support the claim that screening was already implemented there. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • ALD has a birth prevalence of 1:15,000 in male and female patients.

    “ALD has a birth prevalence of 1:15,000 (male patients and female patients).10”

    From International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy (2022) · cites this paper as [10]

    The Introduction reports an estimated minimum birth incidence of about 1 in 17,000 for males and females combined in the United States. The Discussion reports approximately 1 in 14,700 positive newborn screens in New York, close to the claimed 1 in 15,000, but does not present that figure as the overall birth prevalence for males and females. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • cALD is likely less frequent than the previously reported 30-50% of X-ALD patients.

    “However, in light of the recent estimation of overall X-ALD incidence [2], it is likely that cALD is less frequent.”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [2]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

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Cites

Flagged first, then by citations

Research works printed but not linked: 16

  1. [1]Moser HW; Smith KD; Watkins PA; Powers J; Moser AB X-linked adrenoleukodystrophy In The Metabolic and Molecular Bases of Inherited Disease, 8th ed; Scriver CR, Beaudet AL, Sly WS, Valle D, Eds.; McGraw-Hill: New York, NY, USA, 2001; pp. 3257– 3301.
  2. [4]Mosser J; Douar AM; Sarde CO; Kioschis P; Feil R; Moser H; Poustka AM; Mandel JL; Aubourg P Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature 1993, 361, 726– 730. 8441467
  3. [9]Moser AB; Kreiter N; Bezman L; Lu S; Raymond GV; Naidu S; Moser HW Plasma very long chain fatty acids in 3000 peroxisome disease patients and 29,000 controls. Ann. Neurol 1999, 45, 100– 110. 9894883
  4. [10]Mahmood A; Raymond GV; Dubey P; Peters C; Moser HW Survival analysis of hematopoietic cell transplantation for childhood cerebral X-linked adrenoleukodystrophy: A comparison study. Lancet Neurol. 2007, 6, 687– 692. 17618834
  5. [11]Miller WP; Rothman SM; Nascene D; Kivisto T; DeFor TE; Ziegler RS; Eisengart J; Leiser K; Raymond GV; Lund TC; Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: The largest single-institution cohort report. Blood 2011, 118, 1971– 1978. 21586746
  6. [13]Raymond GV; Jones RO; Moser AB Newborn screening for adrenoleukodystrophy: Implications for therapy. Mol. Diagn. Ther 2007, 11, 296– 302. 18078355
  7. [14]Moser HW; Raymond GV; Lu SE; Muenz LR; Moser AB; Xu J; Jones RO; Loes DJ; Melhem ER; Dubey P; Follow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo’s oil. Arch. Neurol 2005, 62, 1073– 1080. 16009761
  8. [15]Moser HW; Moser AB; Hollandsworth K; Brereton NH; Raymond GV “ Lorenzo’s oil” therapy for X-linked adrenoleukodystrophy: Rationale and current assessment of efficacy. J. Mol. Neurosci 2007, 33, 105– 113. 17901554
  9. [16]Lerner BH Complicated lessons: Lorenzo Odone and medical miracles. Lancet 2009, 373, 888– 889. 19291841
  10. [18]Hubbard WC; Moser AB; Liu AC; Raymond GV; Jones RO; Lorey F; Panny S; Vogt RF Jr.; Macaya D; Turgeon CT; Newborn Screening for X-Linked Adrenoleukodystrophy (X-ALD): Validation of a Combined Liquid Chromatography-Tandem Mass Spectrometric (LC-MS/MS) Method. Mol. Genet. Metab 2009, 97, 212– 220. 19423374
  11. [19]Theda C; Gibbons K; DeFor TE; Donohue PK; Golden WC; Kline AD; Gulamali-Majid F; Panny SR; Hubbard WC; Jones RO; Newborn screening for X-linked adrenoleukodystrophy: Further evidence high throughput screening is feasible. Mol. Genet. Metab 2014, 111, 55– 57. 24268529 PMC3935823
  12. [20]Haynes CA; De Jesús VR Improved analysis of C26:0-lysophosphatidylcholine in dried-blood spots via negative ion mode HPLC-ESI-MS/MS for X-linked adrenoleukodystrophy newborn screening. Clin. Chim. Acta 2012, 413, 1217– 1221. 22503909
  13. [21]Turgeon CT; Moser AB; Mørkrid L; Magera MS; Gavrilov DK; Ogelsbee D; Raymond K; Rinaldo P; Matern D; Tortorelli S Streamlined determination of lysophosphatidylcholines in dried blood spots for newborn screening of X-linked adrenoleukodystrophy. Mol. Genet. Metab 2015, 114, 46– 50. 25481105
  14. [22]De Jesús VR; Mei JV; Cordovado SK; Cuthbert CD The Newborn Screening Quality Assurance Program at the Centers for Disease Control and Prevention: Thirty-Five Year Experience Assuring Newborn Screening Laboratory Quality. Int. J. Neonatal Screen. 2015, 1, 13– 26. 26309908 PMC4545740
  15. [23]Vogel BH; Bradley SE; Adams DJ; D’Aco K; Erbe RW; Fong C; Iglesias A; Kronn D; Levy P; Morissey M; Newborn screening for X-linked adrenoleukodystrophy in New York State: Diagnostic protocol, surveillance protocol and treatment guidelines. Mol. Genet. Metab 2015, 114, 599– 603. 25724074
  16. [24]Braverman NE; Raymond GV; Rizzo WB; Moser AB; Wilkinson ME; Stone EM; Steinberg SJ; Wangler MF; Rush ET; Hacia JG; Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol. Genet. Metab 2016, 117, 313– 321. 26750748 PMC5214431

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Authors
Moser, A., Jones, R., Hubbard, W., Tortorelli, S., Orsini, J., Caggana, M., Vogel, B., & Raymond, G.
Affiliations
  • Kennedy Krieger Institute (US)
  • Johns Hopkins University (US)
  • Mayo Clinic (US)
  • New York State Department of Health (US)
  • University of Minnesota Medical Center (US)
Corresponding author
Moser, Ann
ORCID
Venue
International Journal of Neonatal Screening
Publisher
MDPI AG
Published
2016-12-06
Volume
2
Issue
4
Pages
15
ISSN
2409-515X (ISSN-L)
DOI
10.3390/ijns2040015
PMC
PMC6715319
OpenAlex
W2560085362
Cited by
106
References
8
Citations by year
2026: 6 · 2025: 14 · 2024: 13 · 2023: 15 · 2022: 17 · 2021: 19 · 2020: 8 · 2019: 6 · 2018: 6 · 2017: 2
FWCI
4.61
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Neonatal Screening (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Myelin Project
  • Global Foundation for Peroxisomal Disorders
  • Association Européenne contre les Leucodystrophies
  • National Institutes of Health (1s10rr016798-01)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD057136, U54HD079123)
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, adrenal insufficiency, childhood cerebral adrenoleukodystrophy, hematopoietic stem cell transplantation, screening program implementation, follow-up recommendations, New York, Connecticut, California, Netherlands, state legislation

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