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Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania

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Priestley, Jessica R. C., Adang, Laura A., Drewes Williams, Sarah, Lichter-Konecki, Uta, Menello, Caitlin, Engelhardt, Nicole M., DiPerna, James C., DiBoscio, Brenda +4 more·2022·International Journal of Neonatal Screening
DOI 10.3390/ijns8020024PMC PMC9036281
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Abstract

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in ABCD1, which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the disease is particularly devastating. Early diagnosis and intervention improve outcomes. Because newborn screening facilitates identification of at-risk individuals during their asymptomatic period, X-ALD was added to the Pennsylvania newborn screening program in 2017. We analyzed outcomes from the first four years of X-ALD newborn screening, which employed a two-tier approach and reflexive ABCD1 sequencing. There were 51 positive screens with elevated C26:0-lysophosphatidylcholine on second-tier screening. ABCD1 sequencing identified 21 hemizygous males and 24 heterozygous females, and clinical follow up identified four patients with peroxisomal biogenesis disorders. There were two false-positive cases and one false-negative case. Three unscreened individuals, two of whom were symptomatic, were diagnosed following their young siblings’ newborn screening results. Combined with experiences from six other states, this suggests a U.S. incidence of roughly 1 in 10,500, higher than had been previously reported. Many of these infants lack a known family history of X-ALD. Together, these data highlight both the achievements and challenges of newborn screening for X-ALD.

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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 [7]

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Authors
Priestley, J. R. C., Adang, L. A., Drewes Williams, S., Lichter-Konecki, U., Menello, C., Engelhardt, N. M., DiPerna, J. C., DiBoscio, B., Ahrens-Nicklas, R. C., Edmondson, A. C., Reynoso Santos, F. J., & Ficicioglu, C.
Affiliations
  • Children's Hospital of Philadelphia (US)
  • Division of Genetic and Genomic Medicine, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA
  • PerkinElmer (United States) (US)
  • Section of Biochemical Genetics, Division of Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Corresponding author
Ficicioglu, Can
ORCID
Venue
International Journal of Neonatal Screening
Publisher
MDPI AG
Published
2022-03-23
Volume
8
Issue
2
Pages
24
ISSN
2409-515X (ISSN-L)
DOI
10.3390/ijns8020024
PMC
PMC9036281
OpenAlex
W4220711884
Cited by
35
References
7
Citations by year
2026: 7 · 2025: 8 · 2024: 7 · 2023: 9 · 2022: 4
FWCI
4.87
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Neonatal Screening (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Pennsylvania Department of Health
  • Children's Hospital of Philadelphia
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 › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords
X-linked adrenoleukodystrophy, newborn screening, ABCD1, peroxisomal disorders, peroxisome biogenesis disorders, screening outcomes, false positives and false negatives, disease incidence, Pennsylvania

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