Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784693489514053632 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9036281 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT priestleyjessicarc newbornscreeningforxlinkedadrenoleukodystrophyreviewofdataandoutcomesinpennsylvania AT adanglauraa newbornscreeningforxlinkedadrenoleukodystrophyreviewofdataandoutcomesinpennsylvania AT dreweswilliamssarah newbornscreeningforxlinkedadrenoleukodystrophyreviewofdataandoutcomesinpennsylvania AT lichterkoneckiuta newbornscreeningforxlinkedadrenoleukodystrophyreviewofdataandoutcomesinpennsylvania AT menellocaitlin newbornscreeningforxlinkedadrenoleukodystrophyreviewofdataandoutcomesinpennsylvania AT engelhardtnicolem newbornscreeningforxlinkedadrenoleukodystrophyreviewofdataandoutcomesinpennsylvania AT dipernajamesc newbornscreeningforxlinkedadrenoleukodystrophyreviewofdataandoutcomesinpennsylvania AT dibosciobrenda newbornscreeningforxlinkedadrenoleukodystrophyreviewofdataandoutcomesinpennsylvania AT ahrensnicklasrebeccac newbornscreeningforxlinkedadrenoleukodystrophyreviewofdataandoutcomesinpennsylvania AT edmondsonandrewc newbornscreeningforxlinkedadrenoleukodystrophyreviewofdataandoutcomesinpennsylvania AT reynososantosfrancisjeshira newbornscreeningforxlinkedadrenoleukodystrophyreviewofdataandoutcomesinpennsylvania AT ficicioglucan newbornscreeningforxlinkedadrenoleukodystrophyreviewofdataandoutcomesinpennsylvania |