Cargando…

Newborn Screening for X-Linked Adrenoleukodystrophy in Nebraska: Initial Experiences and Challenges

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease caused by pathogenic variants in ABCD1 resulting in defective peroxisomal oxidation of very long-chain fatty acids. Most male patients develop adrenal insufficiency and one of two neurologic phenotypes: a rapidly progressive demyel...

Descripción completa

Detalles Bibliográficos
Autores principales: Baker, Craig V., Cady Keller, Alyssa, Lutz, Richard, Eveans, Karen, Baumert, Krystal, DiPerna, James C., Rizzo, William B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149921/
https://www.ncbi.nlm.nih.gov/pubmed/35645283
http://dx.doi.org/10.3390/ijns8020029
_version_ 1784717309434134528
author Baker, Craig V.
Cady Keller, Alyssa
Lutz, Richard
Eveans, Karen
Baumert, Krystal
DiPerna, James C.
Rizzo, William B.
author_facet Baker, Craig V.
Cady Keller, Alyssa
Lutz, Richard
Eveans, Karen
Baumert, Krystal
DiPerna, James C.
Rizzo, William B.
author_sort Baker, Craig V.
collection PubMed
description X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease caused by pathogenic variants in ABCD1 resulting in defective peroxisomal oxidation of very long-chain fatty acids. Most male patients develop adrenal insufficiency and one of two neurologic phenotypes: a rapidly progressive demyelinating disease in mid-childhood (childhood cerebral X-ALD, ccALD) or an adult-onset spastic paraparesis (adrenomyeloneuropathy, AMN). The neurodegenerative course of ccALD can be halted if patients are treated with hematopoietic stem cell transplantation at the earliest onset of white matter disease. Newborn screening for X-ALD can be accomplished by measuring C26:0-lysophosphatidylcholine in dried blood spots. In Nebraska, X-ALD newborn screening was instituted in July 2018. Over a period of 3.3 years, 82,920 newborns were screened with 13 positive infants detected (4 males, 9 females), giving a birth prevalence of 1:10,583 in males and 1:4510 in females. All positive newborns had DNA variants in ABCD1. Lack of genotype-phenotype correlations, absence of predictive biomarkers for ccALD or AMN, and a high proportion of ABCD1 variants of uncertain significance are unique challenges in counseling families. Surveillance testing for adrenal and neurologic disease in presymptomatic X-ALD males will improve survival and overall quality of life.
format Online
Article
Text
id pubmed-9149921
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-91499212022-05-31 Newborn Screening for X-Linked Adrenoleukodystrophy in Nebraska: Initial Experiences and Challenges Baker, Craig V. Cady Keller, Alyssa Lutz, Richard Eveans, Karen Baumert, Krystal DiPerna, James C. Rizzo, William B. Int J Neonatal Screen Article X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease caused by pathogenic variants in ABCD1 resulting in defective peroxisomal oxidation of very long-chain fatty acids. Most male patients develop adrenal insufficiency and one of two neurologic phenotypes: a rapidly progressive demyelinating disease in mid-childhood (childhood cerebral X-ALD, ccALD) or an adult-onset spastic paraparesis (adrenomyeloneuropathy, AMN). The neurodegenerative course of ccALD can be halted if patients are treated with hematopoietic stem cell transplantation at the earliest onset of white matter disease. Newborn screening for X-ALD can be accomplished by measuring C26:0-lysophosphatidylcholine in dried blood spots. In Nebraska, X-ALD newborn screening was instituted in July 2018. Over a period of 3.3 years, 82,920 newborns were screened with 13 positive infants detected (4 males, 9 females), giving a birth prevalence of 1:10,583 in males and 1:4510 in females. All positive newborns had DNA variants in ABCD1. Lack of genotype-phenotype correlations, absence of predictive biomarkers for ccALD or AMN, and a high proportion of ABCD1 variants of uncertain significance are unique challenges in counseling families. Surveillance testing for adrenal and neurologic disease in presymptomatic X-ALD males will improve survival and overall quality of life. MDPI 2022-04-26 /pmc/articles/PMC9149921/ /pubmed/35645283 http://dx.doi.org/10.3390/ijns8020029 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
Baker, Craig V.
Cady Keller, Alyssa
Lutz, Richard
Eveans, Karen
Baumert, Krystal
DiPerna, James C.
Rizzo, William B.
Newborn Screening for X-Linked Adrenoleukodystrophy in Nebraska: Initial Experiences and Challenges
title Newborn Screening for X-Linked Adrenoleukodystrophy in Nebraska: Initial Experiences and Challenges
title_full Newborn Screening for X-Linked Adrenoleukodystrophy in Nebraska: Initial Experiences and Challenges
title_fullStr Newborn Screening for X-Linked Adrenoleukodystrophy in Nebraska: Initial Experiences and Challenges
title_full_unstemmed Newborn Screening for X-Linked Adrenoleukodystrophy in Nebraska: Initial Experiences and Challenges
title_short Newborn Screening for X-Linked Adrenoleukodystrophy in Nebraska: Initial Experiences and Challenges
title_sort newborn screening for x-linked adrenoleukodystrophy in nebraska: initial experiences and challenges
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149921/
https://www.ncbi.nlm.nih.gov/pubmed/35645283
http://dx.doi.org/10.3390/ijns8020029
work_keys_str_mv AT bakercraigv newbornscreeningforxlinkedadrenoleukodystrophyinnebraskainitialexperiencesandchallenges
AT cadykelleralyssa newbornscreeningforxlinkedadrenoleukodystrophyinnebraskainitialexperiencesandchallenges
AT lutzrichard newbornscreeningforxlinkedadrenoleukodystrophyinnebraskainitialexperiencesandchallenges
AT eveanskaren newbornscreeningforxlinkedadrenoleukodystrophyinnebraskainitialexperiencesandchallenges
AT baumertkrystal newbornscreeningforxlinkedadrenoleukodystrophyinnebraskainitialexperiencesandchallenges
AT dipernajamesc newbornscreeningforxlinkedadrenoleukodystrophyinnebraskainitialexperiencesandchallenges
AT rizzowilliamb newbornscreeningforxlinkedadrenoleukodystrophyinnebraskainitialexperiencesandchallenges