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Cited by 30Metabolism and Genetic DisordersLysosomal Storage Disorders ResearchGenomics and Rare Diseases

Newborn Screening for X-Linked Adrenoleukodystrophy in Georgia: Experiences from a Pilot Study Screening of 51,081 Newborns

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Hall, Patricia L., Li, Hong, Hagar, Arthur F., Jerris, S. Caleb, Wittenauer, Angela, Wilcox, William·2020·International Journal of Neonatal Screening
DOI 10.3390/ijns6040081PMC PMC7711439
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Abstract

We screened 51,081 newborns for X-linked adrenoleukodystrophy (ALD) using a two-tiered strategy quantifying very long chain lysophosphatadylcholines (LPC). Our testing strategy used flow injection tandem mass spectrometry for the first-tier analysis of LPCs, and second-tier quantification of C26:0 LPC using liquid chromatography tandem mass spectrometry. There were 364 specimens considered abnormal using our first-tier algorithm that relied on the four LPC measurements and post-analytical tools. Second-tier test results were reported as normal or abnormal based on a cutoff for the single analyte, C26:0 LPC. Eleven cases were reported as abnormal based on second-tier test results. One male with ALD was identified, and two females with peroxisomal biogenesis disorders were also identified. A single female case remains unresolved, due to a loss to follow up after a negative molecular test result for ABCD1 gene sequencing. The positive predictive value for confirmed, clinically relevant disorders during this pilot study was 27.3%. Challenges identified during the study period were based around coverage for confirmatory testing, particularly if family members needed molecular testing, which is an ongoing issue with newborn screening in Georgia. We also encountered issues with the follow up for a patient who remained asymptomatic. Due to the different timelines involved with clinical findings in ALD, follow-up coordination may be more difficult, particularly if the child identified by newborn screening (NBS) is the only member of the family affected, or able to be tested.

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  • 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 [55]

    The Introduction (page not provided) says New York and other U.S. states implemented newborn screening for ALD, and the Discussion (page not provided) reports that the Georgia pilot identified an infant with ALD presymptomatically. These passages support identification through screening in the United States, but our copy does not address implementation in the Netherlands. (LLM, conf=0.87)

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Research works printed but not linked: 14

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Cited by

Sorted by citations

Authors
Hall, P. L., Li, H., Hagar, A. F., Jerris, S. C., Wittenauer, A., & Wilcox, W.
Affiliations
  • Emory University (US)
  • Georgia Department of Public Health (US)
  • EGL Genetics, Tucker, GA 30084, USA
Corresponding author
Hall, Patricia L.
ORCID
Venue
International Journal of Neonatal Screening
Publisher
MDPI AG
Published
2020-10-23
Volume
6
Issue
4
Pages
81
ISSN
2409-515X (ISSN-L)
DOI
10.3390/ijns6040081
PMC
PMC7711439
OpenAlex
W3093730151
Cited by
30
References
2
Citations by year
2026: 3 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 10 · 2021: 4
FWCI
3.15
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, cc-by-sa)
Funders
Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract #HHSN275201500001I; Task order # HHSN27500002.)
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 › Genetics › Genomics and Rare Diseases
Keywords
X-linked adrenoleukodystrophy, newborn screening, peroxisome biogenesis disorders, ABCD1 gene, positive predictive value, Georgia

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