Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity
For many genetic disorders, there are no specific metabolic biomarkers nor analytical methods suitable for newborn population screening, even where highly effective preemptive treatments are available. The direct measurement of signature peptides as a surrogate marker for the protein in dried blood...
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MDPI AG
2025-01-01
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| Series: | International Journal of Neonatal Screening |
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| Online Access: | https://www.mdpi.com/2409-515X/11/1/6 |
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| author | Claire Klippel Jiwoon Park Sean Sandin Tara M. L. Winstone Xue Chen Dennis Orton Aranjeet Singh Jonathan D. Hill Tareq K. Shahbal Emily Hamacher Brandon Officer John Thompson Phi Duong Tim Grotzer Si Houn Hahn |
| author_facet | Claire Klippel Jiwoon Park Sean Sandin Tara M. L. Winstone Xue Chen Dennis Orton Aranjeet Singh Jonathan D. Hill Tareq K. Shahbal Emily Hamacher Brandon Officer John Thompson Phi Duong Tim Grotzer Si Houn Hahn |
| author_sort | Claire Klippel |
| collection | DOAJ |
| description | For many genetic disorders, there are no specific metabolic biomarkers nor analytical methods suitable for newborn population screening, even where highly effective preemptive treatments are available. The direct measurement of signature peptides as a surrogate marker for the protein in dried blood spots (DBSs) has been shown to successfully identify patients with Wilson Disease (WD) and three life-threatening inborn errors of immunity, X-linked agammaglobulinemia (XLA), Wiskott–Aldrich syndrome (WAS), and adenosine deaminase deficiency (ADAD). A novel proteomic-based multiplex assay to detect these four conditions from DBS using high-throughput LC-MS/MS was developed and validated. The clinical validation results showed that the assay can accurately identify patients of targeted disorders from controls. Additionally, 30,024 newborn DBS samples from the Washington State Department of Health Newborn Screening Laboratory have been screened from 2022 to 2024. One true presumptive positive case of WD was found along with three false positive cases. Five false positives for WAS were detected, but all of them were premature and/or low-birth-weight babies and four of them had insufficient DNA for confirmation. The pilot study demonstrates the feasibility and effectiveness of utilizing this multiplexed proteomic assay for newborn screening. |
| format | Article |
| id | doaj-art-453df06b9cf04ced93c08ff8ac0dd055 |
| institution | OA Journals |
| issn | 2409-515X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Neonatal Screening |
| spelling | doaj-art-453df06b9cf04ced93c08ff8ac0dd0552025-08-20T01:48:46ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2025-01-01111610.3390/ijns11010006Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of ImmunityClaire Klippel0Jiwoon Park1Sean Sandin2Tara M. L. Winstone3Xue Chen4Dennis Orton5Aranjeet Singh6Jonathan D. Hill7Tareq K. Shahbal8Emily Hamacher9Brandon Officer10John Thompson11Phi Duong12Tim Grotzer13Si Houn Hahn14Key Proteo, Inc., Seattle, WA 98122, USAKey Proteo, Inc., Seattle, WA 98122, USAKey Proteo, Inc., Seattle, WA 98122, USAAlberta Precision Laboratories, Calgary, AB T2L 2K8, CanadaAlberta Precision Laboratories, Calgary, AB T2L 2K8, CanadaAlberta Precision Laboratories, Calgary, AB T2L 2K8, CanadaWashington State Department of Health Newborn Screening Laboratories, Seattle, WA 98155, USAWashington State Department of Health Newborn Screening Laboratories, Seattle, WA 98155, USAWashington State Department of Health Newborn Screening Laboratories, Seattle, WA 98155, USAWashington State Department of Health Newborn Screening Laboratories, Seattle, WA 98155, USAWashington State Department of Health Newborn Screening Laboratories, Seattle, WA 98155, USAWashington State Department of Health Newborn Screening Laboratories, Seattle, WA 98155, USASeattle Children’s Research Institute, Seattle, WA 98105, USASeattle Children’s Research Institute, Seattle, WA 98105, USAKey Proteo, Inc., Seattle, WA 98122, USAFor many genetic disorders, there are no specific metabolic biomarkers nor analytical methods suitable for newborn population screening, even where highly effective preemptive treatments are available. The direct measurement of signature peptides as a surrogate marker for the protein in dried blood spots (DBSs) has been shown to successfully identify patients with Wilson Disease (WD) and three life-threatening inborn errors of immunity, X-linked agammaglobulinemia (XLA), Wiskott–Aldrich syndrome (WAS), and adenosine deaminase deficiency (ADAD). A novel proteomic-based multiplex assay to detect these four conditions from DBS using high-throughput LC-MS/MS was developed and validated. The clinical validation results showed that the assay can accurately identify patients of targeted disorders from controls. Additionally, 30,024 newborn DBS samples from the Washington State Department of Health Newborn Screening Laboratory have been screened from 2022 to 2024. One true presumptive positive case of WD was found along with three false positive cases. Five false positives for WAS were detected, but all of them were premature and/or low-birth-weight babies and four of them had insufficient DNA for confirmation. The pilot study demonstrates the feasibility and effectiveness of utilizing this multiplexed proteomic assay for newborn screening.https://www.mdpi.com/2409-515X/11/1/6Wilson DiseaseWiskott–Aldrich syndromeX-linked agammaglobulinemiaadenosine deaminase deficiencynewborn screeningproteomics |
| spellingShingle | Claire Klippel Jiwoon Park Sean Sandin Tara M. L. Winstone Xue Chen Dennis Orton Aranjeet Singh Jonathan D. Hill Tareq K. Shahbal Emily Hamacher Brandon Officer John Thompson Phi Duong Tim Grotzer Si Houn Hahn Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity International Journal of Neonatal Screening Wilson Disease Wiskott–Aldrich syndrome X-linked agammaglobulinemia adenosine deaminase deficiency newborn screening proteomics |
| title | Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity |
| title_full | Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity |
| title_fullStr | Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity |
| title_full_unstemmed | Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity |
| title_short | Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity |
| title_sort | advancing newborn screening in washington state a novel multiplexed lc ms ms proteomic assay for wilson disease and inborn errors of immunity |
| topic | Wilson Disease Wiskott–Aldrich syndrome X-linked agammaglobulinemia adenosine deaminase deficiency newborn screening proteomics |
| url | https://www.mdpi.com/2409-515X/11/1/6 |
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