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

• DOI: 10.3389/fneur.2022.1072256
• Publication Date: 2023-01-10T15:53:45Z
• Authors: Eleonora Bonaventura; Luisella Alberti; Simona Lucchi; Laura Cappelletti; Salvatore Fazzone; Elisa Cattaneo; Matteo Bellini; Giana Izzo; Cecilia Parazzini; Alessandra Bosetti; Elisabetta Di Profio; Giulia Fiore; Matilde Ferrario; Chiara Mameli; Arianna Sangiorgio; Silvia Masnada; Gian Vincenzo Zuc...; Pierangelo Veggiotti; Luigina Spaccini; Maria Iascone; Elvira Verduci; Cristina Cereda; Davide Tonduti
• Keywords: Adrenoleukodystrophy

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