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Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in ABCD1, which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the disease is particu...

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Autores principales: Priestley, Jessica R. C., Adang, Laura A., Drewes Williams, Sarah, Lichter-Konecki, Uta, Menello, Caitlin, Engelhardt, Nicole M., DiPerna, James C., DiBoscio, Brenda, Ahrens-Nicklas, Rebecca C., Edmondson, Andrew C., Reynoso Santos, Francis Jeshira, Ficicioglu, Can
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036281/
https://www.ncbi.nlm.nih.gov/pubmed/35466195
http://dx.doi.org/10.3390/ijns8020024
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author Priestley, Jessica R. C.
Adang, Laura A.
Drewes Williams, Sarah
Lichter-Konecki, Uta
Menello, Caitlin
Engelhardt, Nicole M.
DiPerna, James C.
DiBoscio, Brenda
Ahrens-Nicklas, Rebecca C.
Edmondson, Andrew C.
Reynoso Santos, Francis Jeshira
Ficicioglu, Can
author_facet Priestley, Jessica R. C.
Adang, Laura A.
Drewes Williams, Sarah
Lichter-Konecki, Uta
Menello, Caitlin
Engelhardt, Nicole M.
DiPerna, James C.
DiBoscio, Brenda
Ahrens-Nicklas, Rebecca C.
Edmondson, Andrew C.
Reynoso Santos, Francis Jeshira
Ficicioglu, Can
author_sort Priestley, Jessica R. C.
collection PubMed
description X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in ABCD1, which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the disease is particularly devastating. Early diagnosis and intervention improve outcomes. Because newborn screening facilitates identification of at-risk individuals during their asymptomatic period, X-ALD was added to the Pennsylvania newborn screening program in 2017. We analyzed outcomes from the first four years of X-ALD newborn screening, which employed a two-tier approach and reflexive ABCD1 sequencing. There were 51 positive screens with elevated C26:0-lysophosphatidylcholine on second-tier screening. ABCD1 sequencing identified 21 hemizygous males and 24 heterozygous females, and clinical follow up identified four patients with peroxisomal biogenesis disorders. There were two false-positive cases and one false-negative case. Three unscreened individuals, two of whom were symptomatic, were diagnosed following their young siblings’ newborn screening results. Combined with experiences from six other states, this suggests a U.S. incidence of roughly 1 in 10,500, higher than had been previously reported. Many of these infants lack a known family history of X-ALD. Together, these data highlight both the achievements and challenges of newborn screening for X-ALD.
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spelling pubmed-90362812022-04-26 Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania Priestley, Jessica R. C. Adang, Laura A. Drewes Williams, Sarah Lichter-Konecki, Uta Menello, Caitlin Engelhardt, Nicole M. DiPerna, James C. DiBoscio, Brenda Ahrens-Nicklas, Rebecca C. Edmondson, Andrew C. Reynoso Santos, Francis Jeshira Ficicioglu, Can Int J Neonatal Screen Article X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in ABCD1, which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the disease is particularly devastating. Early diagnosis and intervention improve outcomes. Because newborn screening facilitates identification of at-risk individuals during their asymptomatic period, X-ALD was added to the Pennsylvania newborn screening program in 2017. We analyzed outcomes from the first four years of X-ALD newborn screening, which employed a two-tier approach and reflexive ABCD1 sequencing. There were 51 positive screens with elevated C26:0-lysophosphatidylcholine on second-tier screening. ABCD1 sequencing identified 21 hemizygous males and 24 heterozygous females, and clinical follow up identified four patients with peroxisomal biogenesis disorders. There were two false-positive cases and one false-negative case. Three unscreened individuals, two of whom were symptomatic, were diagnosed following their young siblings’ newborn screening results. Combined with experiences from six other states, this suggests a U.S. incidence of roughly 1 in 10,500, higher than had been previously reported. Many of these infants lack a known family history of X-ALD. Together, these data highlight both the achievements and challenges of newborn screening for X-ALD. MDPI 2022-03-23 /pmc/articles/PMC9036281/ /pubmed/35466195 http://dx.doi.org/10.3390/ijns8020024 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Priestley, Jessica R. C.
Adang, Laura A.
Drewes Williams, Sarah
Lichter-Konecki, Uta
Menello, Caitlin
Engelhardt, Nicole M.
DiPerna, James C.
DiBoscio, Brenda
Ahrens-Nicklas, Rebecca C.
Edmondson, Andrew C.
Reynoso Santos, Francis Jeshira
Ficicioglu, Can
Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania
title Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania
title_full Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania
title_fullStr Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania
title_full_unstemmed Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania
title_short Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania
title_sort newborn screening for x-linked adrenoleukodystrophy: review of data and outcomes in pennsylvania
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036281/
https://www.ncbi.nlm.nih.gov/pubmed/35466195
http://dx.doi.org/10.3390/ijns8020024
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