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Cited by 27Metabolism and Genetic DisordersLysosomal Storage Disorders ResearchNeurological diseases and metabolism

Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring

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Bonaventura, Eleonora, Alberti, Luisella, Lucchi, Simona, Cappelletti, Laura, Fazzone, Salvatore, Cattaneo, Elisa, Bellini, Matteo, Izzo, Giana +16 more·2023·Frontiers in Neurology
DOI 10.3389/fneur.2022.1072256PMC PMC9869129
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Abstract

Introduction: X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder caused by variants in the ABCD1 gene. The main phenotypes observed in men with X-ALD are primary adrenal insufficiency, adrenomyeloneuropathy, and cerebral ALD (cALD). Cerebral ALD consists of a demyelinating progressive cerebral white matter (WM) disease associated with rapid clinical decline and is fatal if left untreated. Hematopoietic stem cell transplantation is the standard treatment for cALD as it stabilizes WM degeneration when performed early in the disease. For this reason, early diagnosis is crucial, and several countries have already implemented their newborn screening programs (NBS) with the assessment of C26:0-lysophosphatidylcholine (C26:0-LPC) values as screening for X-ALD. Methods: In June 2021, an Italian group in Lombardy launched a pilot study for the implementation of X-ALD in the Italian NBS program. A three-tiered approach was adopted, and it involved quantifying the values of C26:0-LPC and other metabolites in dried blood spots with FIA-MS/MS first, followed by the more specific ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique and, finally, the genetic confirmation via focused NGS. Discussion: Genetically confirmed patients are set to undergo a follow-up protocol and are periodically evaluated to promptly start a specific treatment if and when the first signs of brain damage appear, as suggested by international guidelines. A specific disease monitoring protocol has been created based on literature data and personal direct experience. Conclusion: The primary aim of this study was to develop a model able to improve the early diagnosis and subsequent follow-up and timely treatment of X-ALD. Ethics: The study was approved by the local ethics committee. The research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

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  • MRI can detect early demyelinating lesions in X-ALD generally localized in the splenium of the corpus callosum, which progress to involve adjacent parieto-occipital white matter.

    “During the follow-up of a patient’s brother with elevated VLCFAs or a child found positive at neonatal screening, MRI is able to detect early demyelinating lesions generally localized in the splenium of the corpus callosum (a region with a very high density of OLs), which progress to involve the adjacent parieto-occipital white matter [14,31,90,91,92].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [14]

    The Neuroradiological assessment section says MRI can detect early cALD lesions, most often in the genu or splenium of the corpus callosum. It does not describe progression into adjacent parieto-occipital white matter, and it notes that some early lesions may arrest rather than progress. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Authors
Bonaventura, E., Alberti, L., Lucchi, S., Cappelletti, L., Fazzone, S., Cattaneo, E., Bellini, M., Izzo, G., Parazzini, C., Bosetti, A., Di Profio, E., Fiore, G., Ferrario, M., Mameli, C., Sangiorgio, A., Masnada, S., Zuccotti, G. V., Veggiotti, P., Spaccini, L., Iascone, M., Verduci, E., Cereda, C., Tonduti, D., & XALD-NBS Study Group
Affiliations
  • Ospedale dei Bambini Vittore Buzzi (IT)
  • Ospedale Papa Giovanni XXIII (IT)
  • University of Milan (IT)
Corresponding author
  • Bonaventura, Eleonora
  • Tonduti, Davide
ORCID
Venue
Frontiers in Neurology
Publisher
Frontiers Media SA
Published
2023-01-09
Volume
13
Pages
1072256-1072256
ISSN
1664-2295 (ISSN-L)
DOI
10.3389/fneur.2022.1072256
PMC
PMC9869129
OpenAlex
W4313986083
Cited by
27
References
8
Citations by year
2026: 3 · 2025: 8 · 2024: 9 · 2023: 7
FWCI
5.25
Type
journal article
Language
en
Update notices
corrigendum (2024-03-06)
Open access
Licence
Locations
  • Frontiers in Neurology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Ministero della Salute (GR-2019-12368701)
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 › Neurology › Neurological diseases and metabolism
Keywords
X-linked adrenoleukodystrophy, newborn screening, ABCD1 gene, peroxisomal disorders, cerebral adrenoleukodystrophy, adrenomyeloneuropathy, Addison's disease, disease surveillance, hematopoietic stem cell transplantation, dried blood spots, UPLC-MS/MS, diagnostic algorithm, early diagnosis, Italy

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