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

Katie Wiens, Susan A Berry, Hyoung Choi, Amy Gaviglio, Ashish O Gupta, Amy Hietala, Daniel L Kenney-Jung, Troy C Lund, Weston Miller, Rene Pierpont, Gerald Raymond, Holly Winslow, Heather Zierhut, Paul J Orchard

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1205-1213
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Volume179
Issue number7
DOIs
StatePublished - Jul 1 2019

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Adrenoleukodystrophy
Newborn Infant
Adrenal Insufficiency
Lysophosphatidylcholines
Pedigree
Parturition
Phenotype

Keywords

  • ABCD1
  • X-linked adrenoleukodystrophy
  • adrenal insufficiency
  • incidence
  • newborn screen
  • prevalence

Cite this

A report on state-wide implementation of newborn screening for X-linked Adrenoleukodystrophy. / Wiens, Katie; Berry, Susan A; Choi, Hyoung; Gaviglio, Amy; Gupta, Ashish O; Hietala, Amy; Kenney-Jung, Daniel L; Lund, Troy C; Miller, Weston; Pierpont, Rene; Raymond, Gerald; Winslow, Holly; Zierhut, Heather; Orchard, Paul J.

In: American Journal of Medical Genetics, Part A, Vol. 179, No. 7, 01.07.2019, p. 1205-1213.

Research output: Contribution to journalArticle

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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.",
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