A report on state-wide implementation of newborn screening for X-linked Adrenoleukodystrophy
Open accessAbstract
Minnesota became the fourth state to begin newborn screening (NBS) for X‐linked adrenoleukodystrophy (X‐ALD) in 2017. As there is limited retrospective data available on NBS for X‐ALD, we analyzed Minnesota's NBS results from the first year of screening. C26:0 lysophosphatidylcholine (C26:0‐LPC) screening results of 67,836 infants and confirmatory testing (ABCD1 gene and serum VLCFA analysis) for screen positives were obtained. Fourteen infants (nine males, five females) screened positive for X‐ALD and all were subsequently confirmed to have X‐ALD, with zero false positives. The birth prevalence of X‐ALD in screened infants was 1 in 4,845 and 1 in 3,878 males, more than five times previous reported incidences. Pedigrees of affected infants were analyzed, and 17 male (mean age of 17) and 24 female relatives were subsequently diagnosed with X‐ALD. Phenotypes of these family members included self‐reported mild neuropathy symptoms in two males and seven females, and childhood cerebral disease (ccALD) and adrenal insufficiency in one male. We observed fewer cases of ccALD and adrenal insufficiency than expected in male family members (5.9% of males for both) compared to previous observations. Together, these findings suggest that the spectrum of X‐ALD may be broader than previously described and that milder cases may previously have been underrepresented. Other challenges included a high frequency of variants of uncertain significance in ABCD1 and an inability to predict phenotypic severity. We posit that thoughtful planning to address these novel challenges and coordination by dedicated specialists will be imperative for successful implementation of population‐based screening for X‐ALD.
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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 [53]
The Introduction describes implementation of X-ALD newborn screening in U.S. states, and the Discussion reports that 14 infants screened positive in Minnesota and were subsequently confirmed. This supports identification at birth in the United States, but our copy does not address implementation in the Netherlands (searched: Netherlands). (LLM, conf=0.86)
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Mallack, E. J., Gao, K., Engelen, M., & Kemp, S. (2022) · Cells · doi:10.3390/cells11020283 · Cited by 60 · see citing works
Özgür-Günes, Y., Chedik, M., Le Stunff, C., Fovet, C.-M., & Bougnères, P. (2022) · Human Gene Therapy · doi:10.1089/hum.2021.293 · Cited by 10 · see citing works
- Authors
- Wiens, K., Berry, S. A., Choi, H., Gaviglio, A., Gupta, A., Hietala, A., Kenney‐Jung, D., Lund, T., Miller, W., Pierpont, E. I., Raymond, G., Winslow, H., Zierhut, H. A., & Orchard, P. J.
- Affiliations
- University of Minnesota (US)
- Minnesota Department of Health (US)
- Sangamo BioSciences (United States) (US)
- Pennsylvania State University (US)
- Corresponding author
- Orchard, Paul J.
- ORCID
- Venue
- American Journal of Medical Genetics Part A
- Publisher
- Wiley
- Published
- 2019-05-10
- Volume
- 179
- Issue
- 7
- Pages
- 1205-1213
- ISSN
- 1552-4825 (ISSN-L)
- 1552-4833
- PMC
- PMC6619352
- OpenAlex
- W2944092451
- Cited by
- 75
- References
- 5
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 7 · 2023: 9 · 2022: 21 · 2021: 11 · 2020: 10 · 2019: 3
- FWCI
- 7.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal of Medical Genetics Part A (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Minnesota Department of Health
- 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, ABCD1 gene, very long chain fatty acids, childhood cerebral adrenoleukodystrophy, adrenal insufficiency, birth prevalence, variants of uncertain significance, phenotypic spectrum, pedigree analysis, Minnesota
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily D, Member 1, Adolescent, Adrenal Insufficiency, Adrenoleukodystrophy, Adult, Aged, Child, Child, Preschool, Family, Fatty Acids, Female, Humans, Infant, Infant, Newborn, Lysophosphatidylcholines, Male, Middle Aged, Minnesota, Mutation, Pedigree, Phenotype, Severity of Illness Index, Gene Expression, Incidence, Neonatal Screening
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