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 ,  XALD-NBS Study Group , Lista Gianluca , Fontana Paola , Varisco Tiziana , Casati Olivia , Podestà Alberto Fabio , Gibelli Maddalena , Martinelli Stefano , Restelli Roberta , Pogliani Laura Maria , Agistri Roberta , Nedbal Marco Giuseppe , Vaglia Paolo , Tzialla Chryssoula , Magnani Luisa , Sala Elena , Lorioli Laura , Banderali Giuseppe , Ghisleni Diana , Drera Bruno , Frittoli Marta , Lizzoli Francesca , Bellini Marta , Bruni Paola , Giulini Ilaria , Benedetti Valentina , Polimeni Valentina , Salvoni Nadia , Raffaele Masotina , Bellan Cristina , Bottino Roberto , Barera Graziano , Poloniato Antonella , Odoni Marta , Verde Ilaria Dalla , Agosti Massimo , Bossi Angela , Tosi Anna , Bussolini Anna Elisabetta , Risso Francesco Maria , Spinoni Vania , Altamura Nicola , Ballista Patrizia , Di Chio Silvia , Pagani Luciana , Decembrino Lidia , Grignani Michela , Morandi Grazia , Fasolato Valeria Angela , Rossi Lorella , Palumbo Emilio , Lepore Alessandro , Forestieri Maria , Ghirardello Stefano , Civardi Elisa , Adamoli Paolo , Giacchero Roberta , Traina Giovanni , Calzi Patrizia , Pedace Fenesia , Sala Marco 

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

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.1072256

DOI=10.3389/fneur.2022.1072256

ISSN=1664-2295

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 males with X-ALD are primary adrenal insufficiency, adrenomyeloneuropathy and cerebral ALD (cALD). cALD consists in a demyelinating progressive cerebral white matter (WM) disease associated with rapid clinical declining and, if left untreated, is fatal. 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 crucially important, and several countries have already implemented their newborn screening program (NBS) with the assessment of C26:0-lysophosphatidylcoline (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 is adopted, and it involves quantifying the values of C26:0-LPC and other metabolites in dried blood spot with FIA-MS/MS first, with the more specific ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique then, and finally the genetic confirmation via focused NGS. 
Discussion: genetically confirmed patients undergo a follow-up protocol and are periodically evaluated to promptly start a specific treatment if, and when, 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 is 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 is conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest