Frontiers in Neurology (Jan 2023)

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

  • Eleonora Bonaventura,
  • Eleonora Bonaventura,
  • Luisella Alberti,
  • Luisella Alberti,
  • Simona Lucchi,
  • Laura Cappelletti,
  • Salvatore Fazzone,
  • Elisa Cattaneo,
  • Elisa Cattaneo,
  • Matteo Bellini,
  • Giana Izzo,
  • Giana Izzo,
  • Cecilia Parazzini,
  • Cecilia Parazzini,
  • Alessandra Bosetti,
  • Alessandra Bosetti,
  • Elisabetta Di Profio,
  • Giulia Fiore,
  • Matilde Ferrario,
  • Matilde Ferrario,
  • Chiara Mameli,
  • Chiara Mameli,
  • Chiara Mameli,
  • Arianna Sangiorgio,
  • Silvia Masnada,
  • Silvia Masnada,
  • Gian Vincenzo Zuccotti,
  • Gian Vincenzo Zuccotti,
  • Pierangelo Veggiotti,
  • Pierangelo Veggiotti,
  • Pierangelo Veggiotti,
  • Luigina Spaccini,
  • Luigina Spaccini,
  • Maria Iascone,
  • Elvira Verduci,
  • Elvira Verduci,
  • Elvira Verduci,
  • Cristina Cereda,
  • Cristina Cereda,
  • Davide Tonduti,
  • Davide Tonduti,
  • Davide Tonduti,
  • XALD-NBS Study Group,
  • Gianluca Lista,
  • Paola Fontana,
  • Tiziana Varisco,
  • Olivia Casati,
  • Alberto Fabio Podestà,
  • Maddalena Gibelli,
  • Stefano Martinelli,
  • Roberta Restelli,
  • Laura Maria Pogliani,
  • Roberta Agistri,
  • Marco Giuseppe Nedbal,
  • Paolo Vaglia,
  • Chryssoula Tzialla,
  • Luisa Magnani,
  • Elena Sala,
  • Laura Lorioli,
  • Giuseppe Banderali,
  • Diana Ghisleni,
  • Bruno Drera,
  • Marta Frittoli,
  • Francesca Lizzoli,
  • Marta Bellini,
  • Paola Bruni,
  • Ilaria Giulini,
  • Valentina Benedetti,
  • Valentina Polimeni,
  • Nadia Salvoni,
  • Masotina Raffaele,
  • Cristina Bellan,
  • Roberto Bottino,
  • Graziano Barera,
  • Antonella Poloniato,
  • Marta Odoni,
  • Ilaria Dalla Verde,
  • Massimo Agosti,
  • Angela Bossi,
  • Anna Tosi,
  • Anna Elisabetta Bussolini,
  • Francesco Maria Risso,
  • Vania Spinoni,
  • Nicola Altamura,
  • Patrizia Ballista,
  • Silvia Di Chio,
  • Luciana Pagani,
  • Lidia Decembrino,
  • Michela Grignani,
  • Grazia Morandi,
  • Valeria Angela Fasolato,
  • Lorella Rossi,
  • Emilio Palumbo,
  • Alessandro Lepore,
  • Maria Forestieri,
  • Stefano Ghirardello,
  • Elisa Civardi,
  • Paolo Adamoli,
  • Roberta Giacchero,
  • Giovanni Traina,
  • Patrizia Calzi,
  • Fenesia Pedace,
  • Marco Sala

DOI
https://doi.org/10.3389/fneur.2022.1072256
Journal volume & issue
Vol. 13

Abstract

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IntroductionX-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.MethodsIn 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.DiscussionGenetically 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.ConclusionThe 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.EthicsThe 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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