Insights From Minnesota on Newborn Screening for Adrenoleukodystrophy: A 5-Year Update

Our objectives are to report on the outcomes of adrenal insufficiency (AI) and cerebral ALD (cALD) in children diagnosed with X-linked adrenoleukodystrophy (ALD) identified by newborn screening (NBS) in Minnesota in the first 5 years following initiation of NBS in 02/2017. A retrospective chart review was conducted for children diagnosed with ALD via Minnesota NBS from 02/06/2017 through 02/06/2022. Data reviewed included newborn screening data, diagnostic very long chain fatty acid levels, ABCD1 molecular testing results, serial measurements of ACTH and cortisol, and serial brain MRI results. Thirty-two boys and 11 girls were molecularly and/or biochemically confirmed to have ALD. Of these 32 boys, six (2-7 years; median age:18 months) developed AI. Two boys developed cALD and underwent stem cell transplantation, one of whom also has been diagnosed with AI. All the pathogenic/likely pathogenic variants detected during the first 5 years had initial C26:0 lysophosphatidylcholine (C26:0 lysoPC) values over 0.3 μmol/L at the time of newborn screening. The addition of ALD to NBS in Minnesota has allowed for early detection of asymptomatic AI in six young patients and asymptomatic cALD in two patients. Data from our study shows a positive correlation between high newborn screening LysoPC levels and variant pathogenicity.