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 <i>ABCD1</i>, which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | International Journal of Neonatal Screening |
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| Online Access: | https://www.mdpi.com/2409-515X/8/2/24 |
| _version_ | 1827659904792395776 |
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| author | Jessica R. C. Priestley Laura A. Adang Sarah Drewes Williams Uta Lichter-Konecki Caitlin Menello Nicole M. Engelhardt James C. DiPerna Brenda DiBoscio Rebecca C. Ahrens-Nicklas Andrew C. Edmondson Francis Jeshira Reynoso Santos Can Ficicioglu |
| author_facet | Jessica R. C. Priestley Laura A. Adang Sarah Drewes Williams Uta Lichter-Konecki Caitlin Menello Nicole M. Engelhardt James C. DiPerna Brenda DiBoscio Rebecca C. Ahrens-Nicklas Andrew C. Edmondson Francis Jeshira Reynoso Santos Can Ficicioglu |
| author_sort | Jessica R. C. Priestley |
| collection | DOAJ |
| description | X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in <i>ABCD1</i>, 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 <i>ABCD1</i> sequencing. There were 51 positive screens with elevated C26:0-lysophosphatidylcholine on second-tier screening. <i>ABCD1</i> 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. |
| first_indexed | 2024-03-09T23:30:48Z |
| format | Article |
| id | doaj.art-018239cea8904a618109a82df3f1a1e3 |
| institution | Directory Open Access Journal |
| issn | 2409-515X |
| language | English |
| last_indexed | 2024-03-09T23:30:48Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Neonatal Screening |
| spelling | doaj.art-018239cea8904a618109a82df3f1a1e32023-11-23T17:08:26ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2022-03-01822410.3390/ijns8020024Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in PennsylvaniaJessica R. C. Priestley0Laura A. Adang1Sarah Drewes Williams2Uta Lichter-Konecki3Caitlin Menello4Nicole M. Engelhardt5James C. DiPerna6Brenda DiBoscio7Rebecca C. Ahrens-Nicklas8Andrew C. Edmondson9Francis Jeshira Reynoso Santos10Can Ficicioglu11Section of Biochemical Genetics, Division of Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADivision of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADivision of Genetic and Genomic Medicine, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USADivision of Genetic and Genomic Medicine, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USASection of Biochemical Genetics, Division of Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USASection of Biochemical Genetics, Division of Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USAPerkinElmer, Mass Spectroscopy Unit, Pittsburgh, PA 15275, USASection of Biochemical Genetics, Division of Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USASection of Biochemical Genetics, Division of Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USASection of Biochemical Genetics, Division of Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USASection of Biochemical Genetics, Division of Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USASection of Biochemical Genetics, Division of Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USAX-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in <i>ABCD1</i>, 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 <i>ABCD1</i> sequencing. There were 51 positive screens with elevated C26:0-lysophosphatidylcholine on second-tier screening. <i>ABCD1</i> 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.https://www.mdpi.com/2409-515X/8/2/24X-linked adrenoleukodystrophyX-ALDC26:0<i>ABCD1</i>newborn screening |
| spellingShingle | Jessica R. C. Priestley Laura A. Adang Sarah Drewes Williams Uta Lichter-Konecki Caitlin Menello Nicole M. Engelhardt James C. DiPerna Brenda DiBoscio Rebecca C. Ahrens-Nicklas Andrew C. Edmondson Francis Jeshira Reynoso Santos Can Ficicioglu Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania International Journal of Neonatal Screening X-linked adrenoleukodystrophy X-ALD C26:0 <i>ABCD1</i> newborn screening |
| 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 | X-linked adrenoleukodystrophy X-ALD C26:0 <i>ABCD1</i> newborn screening |
| url | https://www.mdpi.com/2409-515X/8/2/24 |
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