{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T18:23:50Z","timestamp":1767983030600,"version":"3.49.0"},"reference-count":67,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["RO1HD0111410"],"award-info":[{"award-number":["RO1HD0111410"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>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\u2013Aldrich 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.<\/jats:p>","DOI":"10.3390\/ijns11010006","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T09:24:42Z","timestamp":1736501082000},"page":"6","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS\/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity"],"prefix":"10.3390","volume":"11","author":[{"given":"Claire","family":"Klippel","sequence":"first","affiliation":[{"name":"Key Proteo, Inc., Seattle, WA 98122, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6181-7557","authenticated-orcid":false,"given":"Jiwoon","family":"Park","sequence":"additional","affiliation":[{"name":"Key Proteo, Inc., Seattle, WA 98122, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Sandin","sequence":"additional","affiliation":[{"name":"Key Proteo, Inc., Seattle, WA 98122, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara M. L.","family":"Winstone","sequence":"additional","affiliation":[{"name":"Alberta Precision Laboratories, Calgary, AB T2L 2K8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Chen","sequence":"additional","affiliation":[{"name":"Alberta Precision Laboratories, Calgary, AB T2L 2K8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3014-3961","authenticated-orcid":false,"given":"Dennis","family":"Orton","sequence":"additional","affiliation":[{"name":"Alberta Precision Laboratories, Calgary, AB T2L 2K8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aranjeet","family":"Singh","sequence":"additional","affiliation":[{"name":"Washington State Department of Health Newborn Screening Laboratories, Seattle, WA 98155, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan D.","family":"Hill","sequence":"additional","affiliation":[{"name":"Washington State Department of Health Newborn Screening Laboratories, Seattle, WA 98155, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tareq K.","family":"Shahbal","sequence":"additional","affiliation":[{"name":"Washington State Department of Health Newborn Screening Laboratories, Seattle, WA 98155, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Hamacher","sequence":"additional","affiliation":[{"name":"Washington State Department of Health Newborn Screening Laboratories, Seattle, WA 98155, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon","family":"Officer","sequence":"additional","affiliation":[{"name":"Washington State Department of Health Newborn Screening Laboratories, Seattle, WA 98155, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Thompson","sequence":"additional","affiliation":[{"name":"Washington State Department of Health Newborn Screening Laboratories, Seattle, WA 98155, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phi","family":"Duong","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Seattle, WA 98105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Grotzer","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Seattle, WA 98105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si Houn","family":"Hahn","sequence":"additional","affiliation":[{"name":"Key Proteo, Inc., Seattle, WA 98122, USA"},{"name":"Seattle Children\u2019s Research Institute, Seattle, WA 98105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1177\/00333549131280S204","article-title":"Newborn Screening: From Guthrie to Whole Genome Sequencing","volume":"128","author":"Caggana","year":"2013","journal-title":"Public Health Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s13023-021-01923-0","article-title":"Essential List of Medicinal Products for Rare Diseases: Recommendations from the IRDiRC Rare Disease Treatment Access Working Group","volume":"16","author":"Gahl","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Collins, C.J., Chang, I.J., Jung, S., Dayuha, R., Whiteaker, J.R., Segundo, G.R.S., Torgerson, T.R., Ochs, H.D., Paulovich, A.G., and Hahn, S.H. (2018). Rapid Multiplexed Proteomic Screening for Primary Immunodeficiency Disorders from Dried Blood Spots. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02756"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1021\/acs.jproteome.6b00828","article-title":"Quantification of ATP7B Protein in Dried Blood Spots by Peptide Immuno-SRM as a Potential Screen for Wilson\u2019s Disease","volume":"16","author":"Jung","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1074\/mcp.M112.022442","article-title":"Multiplexed Quantitation of Endogenous Proteins in Dried Blood Spots by Multiple Reaction Monitoring-Mass Spectrometry","volume":"12","author":"Chambers","year":"2013","journal-title":"Mol. Cell. Proteom."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.cll.2011.07.004","article-title":"Peptide Immunoaffinity Enrichment Coupled with Mass Spectrometry for Peptide and Protein Quantification","volume":"31","author":"Whiteaker","year":"2011","journal-title":"Clin. Lab. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1373\/clinchem.2008.109652","article-title":"Quantification of Thyroglobulin, a Low-Abundance Serum Protein, by Immunoaffinity Peptide Enrichment and Tandem Mass Spectrometry","volume":"54","author":"Hoofnagle","year":"2008","journal-title":"Clin. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nbt.1900","article-title":"A Targeted Proteomics\u2013Based Pipeline for Verification of Biomarkers in Plasma","volume":"29","author":"Whiteaker","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/BF00710283","article-title":"Acylcarnitines in Amniotic Fluid: Application to the Prenatal Diagnosis of Propionic Acidaemia","volume":"16","author":"Chace","year":"1993","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_10","first-page":"1","article-title":"Emerging Technology of Multiplexing in Clinical Diagnostics","volume":"16","author":"Ahmad","year":"2022","journal-title":"Int. J. Health Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1172","DOI":"10.1002\/mgg3.1172","article-title":"The Co-occurrence of Wilson Disease and X-linked Agammaglobulinemia in One Family Highlights the Promising Diagnostic Potential of Proteolytic Analysis","volume":"8","author":"Poskanzer","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1053\/j.gastro.2021.02.052","article-title":"Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease","volume":"160","author":"Collins","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Collins, C.J., Yi, F., Dayuha, R., Whiteaker, J.R., Ochs, H.D., Freeman, A., Su, H.C., Paulovich, A.G., Segundo, G.R.S., and Torgerson, T. (2020). Multiplexed Proteomic Analysis for Diagnosis and Screening of Five Primary Immunodeficiency Disorders from Dried Blood Spots. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00464"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0140-6736(07)60196-2","article-title":"Wilson\u2019s Disease","volume":"369","author":"Ala","year":"2007","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1002\/hep.20601","article-title":"Wilson Disease in Septuagenarian Siblings: Raising the Bar for Diagnosis","volume":"41","author":"Ala","year":"2005","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/nyas.12423","article-title":"Population Screening for Wilson\u2019s Disease","volume":"1315","author":"Hahn","year":"2014","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1046\/j.1442-200x.1999.01096.x","article-title":"Mass Screening for Wilson\u2019s Disease: Results and Recommendations","volume":"41","author":"Yamaguchi","year":"1999","journal-title":"Pediatr. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1067\/mpd.2002.122731","article-title":"Mass Screening for Wilson\u2019s Disease by Measuring Urinary Holoceruloplasmin","volume":"140","author":"Owada","year":"2002","journal-title":"J. Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s10875-020-00758-x","article-title":"Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification","volume":"40","author":"Bousfiha","year":"2020","journal-title":"J. Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s10875-022-01289-3","article-title":"Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee","volume":"42","author":"Tangye","year":"2022","journal-title":"J. Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/01.md.0000229482.27398.ad","article-title":"X-Linked Agammaglobulinemia: Report on a United States Registry of 201 Patients","volume":"85","author":"Winkelstein","year":"2006","journal-title":"Medicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100018","DOI":"10.1016\/j.waojou.2019.100018","article-title":"X-Linked Agammaglobulinemia (XLA): Phenotype, Diagnosis, and Therapeutic Challenges around the World","volume":"12","author":"Abramova","year":"2019","journal-title":"World Allergy Organ. J."},{"key":"ref_23","first-page":"935","article-title":"Anti-Infective Prophylaxis for Primary Immunodeficiencies: What is done in Italian Primary Immunodeficiency Network CenterS (IPINet) and Review of the Literature","volume":"27","author":"Moschese","year":"2014","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3349\/ymj.2008.49.1.28","article-title":"Analysis of Clinical Presentations of Bruton Disease: A Review of 20 Years of Accumulated Data from Pediatric Patients at Severance Hospital","volume":"49","author":"Chun","year":"2008","journal-title":"Yonsei Med. J."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Grammatikos, A., Donati, M., Johnston, S.L., and Gompels, M.M. (2021). Peripheral B Cell Deficiency and Predisposition to Viral Infections: The Paradigm of Immune Deficiencies. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.731643"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.4049\/jimmunol.175.2.1329","article-title":"Genotype-Proteotype Linkage in the Wiskott-Aldrich Syndrome","volume":"175","author":"Lutskiy","year":"2005","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4010","DOI":"10.1182\/blood-2003-05-1592","article-title":"Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): Hotspots, Effect on Transcription, and Translation and Phenotype\/Genotype Correlation","volume":"104","author":"Jin","year":"2004","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.bbmt.2008.10.007","article-title":"Wiskott-Aldrich Syndrome: Diagnosis, Clinical and Laboratory Manifestations, and Treatment","volume":"15","author":"Ochs","year":"2009","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1038\/bmt.2012.31","article-title":"Outcomes Following Hematopoietic Cell Transplantation for Wiskott\u2013Aldrich Syndrome","volume":"47","author":"Shin","year":"2012","journal-title":"Bone Marrow Transpl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1056\/NEJM197804272981701","article-title":"Complete Correction of the Wiskott-Aldrich Syndrome by Allogeneic Bone-Marrow Transplantation","volume":"298","author":"Parkman","year":"1978","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-2776(04)86001-2","article-title":"Adenosine Deaminase Deficiency: Metabolic Basis of Immune Deficiency and Pulmonary Inflammation","volume":"Volume 86","author":"Blackburn","year":"2005","journal-title":"Advances in Immunology"},{"key":"ref_32","unstructured":"Hershfield, M., and Tarrant, T. (2006). Adenosine Deaminase Deficiency, GeneReviews."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.jpeds.2009.05.026","article-title":"Identification of Severe Combined Immunodeficiency by T-Cell Receptor Excision Circles Quantification Using Neonatal Guthrie Cards","volume":"155","author":"Morinishi","year":"2009","journal-title":"J. Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e2020005579","DOI":"10.1542\/peds.2020-005579","article-title":"Delayed-Onset ADA1 (ADA) Deficiency Not Detected by TREC Screen","volume":"147","author":"Kahwash","year":"2021","journal-title":"Pediatrics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/j.jaci.2012.08.054","article-title":"Tandem Mass Spectrometry, but Not T-Cell Receptor Excision Circle Analysis, Identifies Newborns with Late-Onset Adenosine Deaminase Deficiency","volume":"131","author":"Canessa","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1007\/s10875-018-0496-9","article-title":"ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome","volume":"38","author":"Cagdas","year":"2018","journal-title":"J. Clin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.ymthe.2017.12.022","article-title":"Gene Therapy for Adenosine Deaminase Deficiency: A Comprehensive Evaluation of Short- and Medium-Term Safety","volume":"26","author":"Cicalese","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1001\/jama.295.5.508","article-title":"Bone Marrow Transplantation for Severe Combined Immune Deficiency","volume":"295","author":"Grunebaum","year":"2006","journal-title":"JAMA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jaci.2004.10.012","article-title":"Development of Population-Based Newborn Screening for Severe Combined Immunodeficiency","volume":"115","author":"Chan","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1749-6632.2011.06350.x","article-title":"Newborn Screening for Primary Immunodeficiencies: Beyond SCID and XLA","volume":"1246","author":"Borte","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"355","DOI":"10.2500\/aap.2024.45.240051","article-title":"Diagnostic Tests for Primary Immunodeficiency Disorders: Classic and Genetic Testing","volume":"45","author":"Klangkalya","year":"2024","journal-title":"Allergy Asthma Proc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s12016-021-08876-z","article-title":"Newborn Screening in the Diagnosis of Primary Immunodeficiency","volume":"63","author":"Kobrynski","year":"2021","journal-title":"Clinic. Rev. Allerg. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1007\/s10875-021-01107-2","article-title":"Second Tier Testing to Reduce the Number of Non-Actionable Secondary Findings and False-Positive Referrals in Newborn Screening for Severe Combined Immunodeficiency","volume":"41","author":"Blom","year":"2021","journal-title":"J. Clin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3390\/ijns1020069","article-title":"Influence of Hematocrit and Total-Spot Volume on Performance Characteristics of Dried Blood Spots for Newborn Screening","volume":"1","author":"Hall","year":"2015","journal-title":"Int. J. Neonatal Screen."},{"key":"ref_45","unstructured":"Clinical and Laboratory Standards Institute (2022). Liquid Chromatography-Mass Spectrometry Methods, CLSI. [2nd ed.]. Approved Guideline, C62."},{"key":"ref_46","unstructured":"Clinical and Laboratory Standards Institute (2021). Quantitative Measurement of Proteins and Peptides by Mass Spectrometry, CLSI. [1st ed.]. Approved Guideline, C64."},{"key":"ref_47","unstructured":"Clinical and Laboratory Standards Institute (2014). Evaluation of Precision of Quantitative Measurement Procedures, CLSI. [3rd ed.]. Approved Guideline, EP05-A3."},{"key":"ref_48","unstructured":"Clinical and Laboratory Standards Institute (2018). Interference Testing in Clinical Chemistry, CLSI. [3rd ed.]. Approved Guideline, EP07."},{"key":"ref_49","unstructured":"Clinical and Laboratory Standards Institute (2018). Supplemental Tables for Interference Testing in Clinical Chemistry, CLSI. [1st ed.]. EP37."},{"key":"ref_50","unstructured":"Clinical and Laboratory Standards Institute (2009). Evaluation of Stability of In Vitro Diagnostic Reagents, CLSI. Approved Guideline, EP25."},{"key":"ref_51","unstructured":"Clinical and Laboratory Standards Institute (2012). Evaluation of Detection Capability, CLSI. [2nd ed.]. EP17-A2."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1093\/bioinformatics\/btq054","article-title":"Skyline: An Open Source Document Editor for Creating and Analyzing Targeted Proteomics Experiments","volume":"26","author":"MacLean","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1590\/2176-9451.19.4.027-029.ebo","article-title":"How Sample Size Influences Research Outcomes","volume":"19","author":"Faber","year":"2014","journal-title":"Dental Press J. Orthod."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6047","DOI":"10.1016\/j.vaccine.2016.03.045","article-title":"Preterm Birth: Case Definition & Guidelines for Data Collection, Analysis, and Presentation of Immunisation Safety Data","volume":"34","author":"Quinn","year":"2016","journal-title":"Vaccine"},{"key":"ref_55","first-page":"723","article-title":"Reduction in Newborn Screening False Positive Results Following a New Collection Protocol: A Quality Improvement Project","volume":"26","author":"Kamleh","year":"2021","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"623","DOI":"10.5144\/0256-4947.2012.623","article-title":"Wilson Disease in 71 Patients Followed for over Two Decades in a Tertiary Center in Saudi Arabia: A Retrospective Review","volume":"32","author":"Helmy","year":"2012","journal-title":"Ann. Saudi Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/(SICI)1098-1004(1998)11:2<145::AID-HUMU7>3.0.CO;2-I","article-title":"Novel ATP7B Mutations Causing Wilson Disease in Several Israeli Ethnic Groups","volume":"11","author":"Kalinsky","year":"1998","journal-title":"Hum. Mutat."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1046\/J.1469-1809.2005.00171.x","article-title":"Wilson Disease: High Prevalence in a Mountaineous Area of Crete","volume":"69","author":"Dedoussis","year":"2005","journal-title":"Ann. Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00439-006-0202-5","article-title":"Regional Distribution of Mutations of the ATP7B Gene in Patients with Wilson Disease: Impact on Genetic Testing","volume":"120","author":"Ferenci","year":"2006","journal-title":"Hum. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/(SICI)1098-1004(199910)14:4<294::AID-HUMU4>3.0.CO;2-9","article-title":"Molecular Characterization of Wilson Disease in the Sardinian Population? Evidence of a Founder Effect","volume":"14","author":"Loudianos","year":"1999","journal-title":"Hum. Mutat."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7716","DOI":"10.3748\/wjg.v23.i43.7716","article-title":"Epidemiology and Natural History of Wilson\u2019s Disease in the Chinese: A Territory-Based Study in Hong Kong between 2000 and 2016","volume":"23","author":"Cheung","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.clinre.2017.05.011","article-title":"Characteristics and Prevalence of Wilson\u2019s Disease: A 2013 Observational Population-Based Study in France","volume":"42","author":"Poujois","year":"2018","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_63","unstructured":"Massingale, S.P., Williams, A.M., Rollin, D.M., Morris, D., Green, L., and Kennedy, D. (2019). Newborn Screening Collection Guidelines, Alabama Department of Public Health Bureau of Clinical Laboratories."},{"key":"ref_64","unstructured":"Washington State Department of Health (2019). The Complete Guide to Newborn Screening in Washington State, Washington State Department of Health."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1111\/cge.13120","article-title":"Diagnosis of Monogenic Liver Diseases in Childhood by Next-generation Sequencing","volume":"93","author":"Stalke","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s10875-011-9609-4","article-title":"Newborn Screening for Severe Combined Immunodeficiency; The Wisconsin Experience (2008\u20132011)","volume":"32","author":"Verbsky","year":"2012","journal-title":"J. Clin. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s10875-014-0006-7","article-title":"Newborn Screening for SCID in New York State: Experience from the First Two Years","volume":"34","author":"Vogel","year":"2014","journal-title":"J. Clin. Immunol."}],"container-title":["International Journal of Neonatal Screening"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2409-515X\/11\/1\/6\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:26:37Z","timestamp":1759919197000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2409-515X\/11\/1\/6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,10]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijns11010006"],"URL":"https:\/\/doi.org\/10.3390\/ijns11010006","relation":{},"ISSN":["2409-515X"],"issn-type":[{"value":"2409-515X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,10]]}}}