Back to Search Start Over

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

Authors :
Holly Winslow
Weston P. Miller
Ashish Gupta
Daniel L. Kenney-Jung
Gerald Raymond
Heather Zierhut
Susan A. Berry
Amy Hietala
Troy C. Lund
Paul J. Orchard
Hyoung Gwon Choi
Elizabeth I. Pierpont
Katie Wiens
Amy Gaviglio
Source :
American Journal of Medical Genetics. Part a
Publication Year :
2019
Publisher :
John Wiley & Sons, Inc., 2019.

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.

Details

Language :
English
ISSN :
15524833 and 15524825
Volume :
179
Issue :
7
Database :
OpenAIRE
Journal :
American Journal of Medical Genetics. Part a
Accession number :
edsair.doi.dedup.....e29ff9e9cd5a0de89327b05539fc177a