{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T08:02:15Z","timestamp":1781078535564,"version":"3.54.1"},"reference-count":11,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ORISE through the U.S. Department of Energy Oak Ridge Institute for Science and Education"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>Lysosomal diseases (LDs, or Lysosomal Storage Disorders) have become increasingly visible in the newborn screening community, with the addition of mucopolysaccharidosis type II (MPS-II) into the Recommended Uniform Screening Panel in August 2022 and Infantile Krabbe disease in June 2024. As more LDs are expected to be considered for screening adoption, the ability to multiplex conditions and expand proficiency testing (PT) using quality control materials is essential. This study examines the use of recombinant enzymes to produce first-tier PT materials for mucopolysaccharidosis type I, MPS-II, Gaucher, Fabry, Krabbe, Pompe, and Niemann\u2013Pick A\/B (acid sphingomyelinase deficiency)\u2014adding four disorders to the CDC\u2019s Newborn Screening Quality Assurance Program (NSQAP) LD PT panel. Through an iterative process that included two prototype phases, two pilot phases, and external testing by up to 31 external laboratories, a new manufacturing process was developed for producing high-performing dried blood spot-based LD PT specimens. Materials were evaluated using several methods commonly employed by newborn screening laboratories, including tandem mass spectrometry with flow injection and liquid chromatography, digital microfluidics, and fluorometric assays. This novel process for producing LD PT materials offers several advantages over previous manufacturing methods that relied on immortalized cell lines from affected patients. Improved scalability, for example, has enabled NSQAP to expand LD PT enrollment internationally. Furthermore, the new process makes it easier to support future expansions of the LD screening panel. The updated specimens and expanded program were launched in January 2025.<\/jats:p>","DOI":"10.3390\/ijns12020040","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:33:44Z","timestamp":1781073224000},"page":"40","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of Dried Blood Spot Proficiency Testing Materials for Newborn Screening of Lysosomal Diseases Using Recombinant Enzymes"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5304-8126","authenticated-orcid":false,"given":"Elya","family":"Courtney","sequence":"first","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6761-2832","authenticated-orcid":false,"given":"Samantha L.","family":"Isenberg","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1632-5777","authenticated-orcid":false,"given":"C. Austin","family":"Pickens","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1852-9477","authenticated-orcid":false,"given":"Rachel","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Cuthbert","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8660-8532","authenticated-orcid":false,"given":"Konstantinos","family":"Petritis","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pickens, C.A., Sternberg, M., Seeterlin, M., De Jes\u00fas, V.R., Morrissey, M., Manning, A., Bhakta, S., Held, P.K., Mei, J., and Cuthbert, C. (2020). Harmonizing Newborn Screening Laboratory Proficiency Test Results Using the CDC NSQAP Reference Materials. Int. J. Neonatal Screen., 6.","DOI":"10.3390\/ijns6030075"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s10995-015-1869-9","article-title":"Evaluating Harms in the Assessment of Net Benefit: A Framework for Newborn Screening Condition Review","volume":"20","author":"Goldenberg","year":"2016","journal-title":"Matern. Child Health J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1001\/jamapediatrics.2020.1522","article-title":"Ending the Diagnostic Odyssey-Is Whole-Genome Sequencing the Answer?","volume":"174","author":"Wu","year":"2020","journal-title":"JAMA Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1053\/j.semperi.2009.12.003","article-title":"Improving and assuring newborn screening laboratory quality worldwide: 30-year experience at the Centers for Disease Control and Prevention","volume":"34","author":"Mei","year":"2010","journal-title":"Semin. Perinatol."},{"key":"ref_5","unstructured":"Association of Public Health Laboratories (2026, March 26). Newborn Screening Technical Assistance and Evaluation Program (NewSTEPs). Available online: http:\/\/www.newsteps.org."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dantonio, P., Klug, T., Yazdanpanah, G., Haynes, C., Zhou, H., Hopkins, P., Vogt, R., Lee, R., Cuthbert, C., and Petritis, K. (2025). Characterization of Dried Blood Spot Quality Control Materials for Lysosomal Enzyme Activity Assays Using Digital Microfluidic Fluorometry to Detect Lysosomal Storage Disorders in Newborns. Int. J. Neonatal Screen., 11.","DOI":"10.3390\/ijns11020044"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.clinbiochem.2014.12.009","article-title":"Galactose-1-phosphate uridyltransferase dried blood spot quality control materials for newborn screening tests","volume":"48","author":"Adam","year":"2015","journal-title":"Clin. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.dib.2016.06.052","article-title":"Dataset and standard operating procedure for newborn screening of six lysosomal storage diseases: By tandem mass spectrometry","volume":"8","author":"Elliott","year":"2016","journal-title":"Data Brief."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gelb, M.H., Lukacs, Z., Ranieri, E., and Schielen, P. (2019). Newborn Screening for Lysosomal Storage Disorders: Methodologies for Measurement of Enzymatic Activities in Dried Blood Spots. Int. J. Neonatal Screen., 5.","DOI":"10.3390\/ijns5010001"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Courtney, E., Pickens, C.A., Cuthbert, C., and Petritis, K. (2023). Multiplexing Iduronate-2-Sulphatase (MPS-II) into a 7-Plex Lysosomal Storage Disorder MS\/MS Assay Using Cold-Induced Phase Separation. Int. J. Neonatal Screen., 9.","DOI":"10.3390\/ijns9020032"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Dorley, M.C., Dizikes, G.J., Pickens, C.A., Cuthbert, C., Basheeruddin, K., Gulamali-Majid, F., Hetterich, P., Hietala, A., Kelsey, A., and Klug, T. (2023). Harmonization of Newborn Screening Results for Pompe Disease and Mucopolysaccharidosis Type I. Int. J. Neonatal Screen., 9.","DOI":"10.3390\/ijns9010011"}],"container-title":["International Journal of Neonatal Screening"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2409-515X\/12\/2\/40\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T07:33:22Z","timestamp":1781076802000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2409-515X\/12\/2\/40"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":11,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijns12020040"],"URL":"https:\/\/doi.org\/10.3390\/ijns12020040","relation":{},"ISSN":["2409-515X"],"issn-type":[{"value":"2409-515X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]}}}