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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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 |
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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 |
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