Adrenoleukodystrophy Newborn Screening in California Since 2016: Programmatic Outcomes and Follow-Up

Abstract

X-linked adrenoleukodystrophy (ALD) is a recent addition to the Recommended Uniform Screening Panel, prompting many states to begin screening newborns for the disorder. We provide California's experience with ALD newborn screening, highlighting the clinical and epidemiological outcomes observed as well as program implementation challenges. In this retrospective cohort study, we examine ALD newborn screening results and clinical outcomes for 1,854,631 newborns whose specimens were received by the California Genetic Disease Screening Program from 16 February 2016 through 15 February 2020. In the first four years of ALD newborn screening in California, 355 newborns screened positive for ALD, including 147 (41%) with an ABCD1 variant of uncertain significance (VUS) and 95 males diagnosed with ALD. After modifying cutoffs, we observed an ALD birth prevalence of 1 in 14,397 males. Long-term follow-up identified 14 males with signs of adrenal involvement. This study adds to a growing body of literature reporting on outcomes of newborn screening for ALD and offering a glimpse of what other large newborn screening programs can expect when adding ALD to their screening panel.

Keywords: adrenoleukodystrophy; evaluation; follow-up; newborn screening.

Figure 1

California adrenoleukodystrophy (ALD) newborn screening and follow-up algorithm. ^a FIA-MS/MS = flow injection analysis-tandem mass spectrometry. ^b LC-MS/M = liquid chromatography-tandem mass spectrometry. ^c The 2nd tier cutoff was originally set at ≥0.15 µmol/L, but was adjusted to ≥0.22 µmol/L in December 2017 to improve screening performance. ^d ABCD1 = ATP binding cassette subfamily D member 1 gene.

Figure 2

Distribution of C26 values at (a) first and (b) second tiers of ALD screening for specimens received 21 September 2016 through 15 February 2020. Screen positive data was included in this analysis for specimens received from 16 February 2016 through 15 February 2020. Screen negative data were not available in our Screening Information System before the system went live on 21 September 2016, and were therefore not included in this analysis. Diamond symbols represent the mean. Open circles are outliers beyond 1.5 times the interquartile range.