Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan 9:13:1072256.
doi: 10.3389/fneur.2022.1072256. eCollection 2022.

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

Eleonora Bonaventura  1   2 , Luisella Alberti  2   3 , Simona Lucchi  3 , Laura Cappelletti  3 , Salvatore Fazzone  3 , Elisa Cattaneo  2   4 , Matteo Bellini  5 , Giana Izzo  2   6 , Cecilia Parazzini  2   6 , Alessandra Bosetti  2   7 , Elisabetta Di Profio  7 , Giulia Fiore  7 , Matilde Ferrario  2   7 , Chiara Mameli  2   7   8 , Arianna Sangiorgio  7 , Silvia Masnada  1   2 , Gian Vincenzo Zuccotti  7   8 , Pierangelo Veggiotti  1   2   8 , Luigina Spaccini  2   4 , Maria Iascone  5 , Elvira Verduci  2   7   9 , Cristina Cereda  2   3 , Davide Tonduti  1   2   8 ; XALD-NBS Study Group
Collaborators, Affiliations

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

Eleonora Bonaventura et al. Front Neurol. .

Erratum in

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.

Keywords: Aicardi-Goutières syndrome (AGS); C26:0-lysophosphatidylcholine; DBS; X-ALD; X-linked adrenoleukodystrophy (X-ALD); Zellweger Spectrum Disorders; hematopoietic stem cell transplantation (HCST); newborn screening (NBS).

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Diagnostic process of X-ALD newborn screening.
Figure 2
Figure 2
Timing of monitoring of pre-symptomatic ABCD1-mutated males subjects.
See this image and copyright information in PMC

References

    1. Moser AB, Jones RO, Hubbard WC, Tortorelli S, Orsini JJ, Caggana M, et al. . Newborn screening for X-linked adrenoleukodystrophy. Int J Neonatal Screen. (2016) 2:15. 10.3390/ijns2040015 - DOI - PMC - PubMed
    1. Kemp S, Wanders RJA. X-linked adrenoleukodystrophy: Very long-chain fatty acid metabolism, ABC half-transporters and the complicated route to treatment. Mol Genet Metab. (2007) 90:268–76. 10.1016/j.ymgme.2006.10.001 - DOI - PubMed
    1. Bezman L, Moser AB, Raymond GV, Rinaldo P, Watkins PA, Smith KD, et al. . Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screening. Ann Neurol. (2001) 49:512–7. 10.1002/ana.101 - DOI - PubMed
    1. Moser HW, Mahmood A, Raymond GV. X-linked adrenoleukodystrophy. Nat Clin Pract Neurol. (2007) 3:140–51. 10.1038/ncpneuro0421 - DOI - PubMed
    1. Turk BR, Theda C, Fatemi A, Moser AB. X-linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies. Int J Dev Neurosci. (2020) 80:52–72. 10.1002/jdn.10003 - DOI - PMC - PubMed