Disease Outcomes in Boys with ABCD1 Variants Identified by Newborn Screening for X-ALD

Objectives To determine whether boys with VUS detected through newborn screening (NBS) for adrenoleukodystrophy (ALD) develop adrenal insufficiency (aiALD) and cerebral ALD (cALD) at rates comparable to those with pathogenic variants, and to evaluate the relationship between C26:0-lysophosphatidylcholine (C26:0-LPC) levels and clinical outcomes. Methods We conducted a retrospective multicenter cohort study (2013 - 2025) across six US centers, including 201 males identified through NBS in 19 states. Variants were classified as pathogenic (n=65), likely pathogenic (n=45), or VUS (n=88). Primary outcomes were development of aiALD and cALD; secondary outcomes included C26:0-LPC levels. Statistic