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. 2019 Jul;179(7):1205-1213.
doi: 10.1002/ajmg.a.61171. Epub 2019 May 10.

A report on state-wide implementation of newborn screening for X-linked Adrenoleukodystrophy

Katie Wiens  1 , Susan A Berry  1 , Hyoung Choi  2 , Amy Gaviglio  3 , Ashish Gupta  4 , Amy Hietala  3 , Daniel Kenney-Jung  2 , Troy Lund  4 , Weston Miller  5 , Elizabeth I Pierpont  6 , Gerald Raymond  7 , Holly Winslow  3 , Heather A Zierhut  8 , Paul J Orchard  4
Affiliations

A report on state-wide implementation of newborn screening for X-linked Adrenoleukodystrophy

Katie Wiens et al. Am J Med Genet A. 2019 Jul.

Abstract

Minnesota became the fourth state to begin newborn screening (NBS) for X-linked adrenoleukodystrophy (X-ALD) in 2017. As there is limited retrospective data available on NBS for X-ALD, we analyzed Minnesota's NBS results from the first year of screening. C26:0 lysophosphatidylcholine (C26:0-LPC) screening results of 67,836 infants and confirmatory testing (ABCD1 gene and serum VLCFA analysis) for screen positives were obtained. Fourteen infants (nine males, five females) screened positive for X-ALD and all were subsequently confirmed to have X-ALD, with zero false positives. The birth prevalence of X-ALD in screened infants was 1 in 4,845 and 1 in 3,878 males, more than five times previous reported incidences. Pedigrees of affected infants were analyzed, and 17 male (mean age of 17) and 24 female relatives were subsequently diagnosed with X-ALD. Phenotypes of these family members included self-reported mild neuropathy symptoms in two males and seven females, and childhood cerebral disease (ccALD) and adrenal insufficiency in one male. We observed fewer cases of ccALD and adrenal insufficiency than expected in male family members (5.9% of males for both) compared to previous observations. Together, these findings suggest that the spectrum of X-ALD may be broader than previously described and that milder cases may previously have been underrepresented. Other challenges included a high frequency of variants of uncertain significance in ABCD1 and an inability to predict phenotypic severity. We posit that thoughtful planning to address these novel challenges and coordination by dedicated specialists will be imperative for successful implementation of population-based screening for X-ALD.

Keywords: ABCD1; X-linked adrenoleukodystrophy; adrenal insufficiency; incidence; newborn screen; prevalence.

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Conflict of interest statement

Heather Zierhut is on the Board of Directors of GeneMatters, LLC, a remote telehealth genetic counseling company. Weston Miller is a full time employee at Sangamo Therapeutics.

Figures

Figure 1
Figure 1
Flowchart demonstrating results of infants screened for ALD on NBS during Minnesota's first year of screening. ALD, adrenoleukodystrophy; NBS, newborn screening
See this image and copyright information in PMC

References

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