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

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 dem...

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Autores principales: Bonaventura, Eleonora, Alberti, Luisella, Lucchi, Simona, Cappelletti, Laura, Fazzone, Salvatore, Cattaneo, Elisa, Bellini, Matteo, Izzo, Giana, Parazzini, Cecilia, Bosetti, Alessandra, Di Profio, Elisabetta, Fiore, Giulia, Ferrario, Matilde, Mameli, Chiara, Sangiorgio, Arianna, Masnada, Silvia, Zuccotti, Gian Vincenzo, Veggiotti, Pierangelo, Spaccini, Luigina, Iascone, Maria, Verduci, Elvira, Cereda, Cristina, Tonduti, Davide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869129/
https://www.ncbi.nlm.nih.gov/pubmed/36698902
http://dx.doi.org/10.3389/fneur.2022.1072256
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author Bonaventura, Eleonora
Alberti, Luisella
Lucchi, Simona
Cappelletti, Laura
Fazzone, Salvatore
Cattaneo, Elisa
Bellini, Matteo
Izzo, Giana
Parazzini, Cecilia
Bosetti, Alessandra
Di Profio, Elisabetta
Fiore, Giulia
Ferrario, Matilde
Mameli, Chiara
Sangiorgio, Arianna
Masnada, Silvia
Zuccotti, Gian Vincenzo
Veggiotti, Pierangelo
Spaccini, Luigina
Iascone, Maria
Verduci, Elvira
Cereda, Cristina
Tonduti, Davide
author_facet Bonaventura, Eleonora
Alberti, Luisella
Lucchi, Simona
Cappelletti, Laura
Fazzone, Salvatore
Cattaneo, Elisa
Bellini, Matteo
Izzo, Giana
Parazzini, Cecilia
Bosetti, Alessandra
Di Profio, Elisabetta
Fiore, Giulia
Ferrario, Matilde
Mameli, Chiara
Sangiorgio, Arianna
Masnada, Silvia
Zuccotti, Gian Vincenzo
Veggiotti, Pierangelo
Spaccini, Luigina
Iascone, Maria
Verduci, Elvira
Cereda, Cristina
Tonduti, Davide
author_sort Bonaventura, Eleonora
collection PubMed
description 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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spelling pubmed-98691292023-01-24 Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring Bonaventura, Eleonora Alberti, Luisella Lucchi, Simona Cappelletti, Laura Fazzone, Salvatore Cattaneo, Elisa Bellini, Matteo Izzo, Giana Parazzini, Cecilia Bosetti, Alessandra Di Profio, Elisabetta Fiore, Giulia Ferrario, Matilde Mameli, Chiara Sangiorgio, Arianna Masnada, Silvia Zuccotti, Gian Vincenzo Veggiotti, Pierangelo Spaccini, Luigina Iascone, Maria Verduci, Elvira Cereda, Cristina Tonduti, Davide Front Neurol Neurology 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. Frontiers Media S.A. 2023-01-09 /pmc/articles/PMC9869129/ /pubmed/36698902 http://dx.doi.org/10.3389/fneur.2022.1072256 Text en Copyright © 2023 Bonaventura, Alberti, Lucchi, Cappelletti, Fazzone, Cattaneo, Bellini, Izzo, Parazzini, Bosetti, Di Profio, Fiore, Ferrario, Mameli, Sangiorgio, Masnada, Zuccotti, Veggiotti, Spaccini, Iascone, Verduci, Cereda, Tonduti and XALD-NBS Study Group. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Bonaventura, Eleonora
Alberti, Luisella
Lucchi, Simona
Cappelletti, Laura
Fazzone, Salvatore
Cattaneo, Elisa
Bellini, Matteo
Izzo, Giana
Parazzini, Cecilia
Bosetti, Alessandra
Di Profio, Elisabetta
Fiore, Giulia
Ferrario, Matilde
Mameli, Chiara
Sangiorgio, Arianna
Masnada, Silvia
Zuccotti, Gian Vincenzo
Veggiotti, Pierangelo
Spaccini, Luigina
Iascone, Maria
Verduci, Elvira
Cereda, Cristina
Tonduti, Davide
Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring
title Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring
title_full Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring
title_fullStr Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring
title_full_unstemmed Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring
title_short Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring
title_sort newborn screening for x-linked adrenoleukodystrophy in italy: diagnostic algorithm and disease monitoring
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869129/
https://www.ncbi.nlm.nih.gov/pubmed/36698902
http://dx.doi.org/10.3389/fneur.2022.1072256
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