{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:31:04Z","timestamp":1781152264758,"version":"3.54.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,9,1]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Interest in lysosomal storage disorders, a collection of more than 40 inherited metabolic disorders, has increased because of new therapy options such as enzyme replacement, stem cell transplantation, and substrate reduction therapy. We developed a high-throughput protocol that simplifies analytical challenges such as complex sample preparation and potential interference from excess residual substrate associated with previously reported assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>After overnight incubation (16\u201320 h) of dried blood spots with a cassette of substrates and deuterated internal standards, we used a TLX-2 system to quantify 6 lysosomal enzyme activities for Fabry, Gaucher, Niemann-Pick A\/B, Pompe, Krabbe, and mucopolysaccharidosis I disease. This multiplexed, multidimensional ultra-HPLC\u2013tandem mass spectrometry assay included Cyclone P Turbo Flow and Hypersil Gold C8 columns. The method did not require offline sample preparation such as liquid\u2013liquid and solid-phase extraction, or hazardous reagents such as ethyl acetate.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Obviating the offline sample preparation steps led to substantial savings in analytical time (approximately 70%) and reagent costs (approximately 50%). In a pilot study, lysosomal enzyme activities of 8586 newborns were measured, including 51 positive controls, and the results demonstrated 100% diagnostic sensitivity and high specificity. The results for Krabbe disease were validated with parallel measurements by the New York State Screening Laboratory.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Turboflow online sample cleanup and the use of an additional analytical column enabled the implementation of lysosomal storage disorder testing in a nationwide screening program while keeping the total analysis time to &amp;lt;2 min per sample.<\/jats:p><\/jats:sec>","DOI":"10.1373\/clinchem.2011.164640","type":"journal-article","created":{"date-parts":[[2011,7,20]],"date-time":"2011-07-20T03:47:36Z","timestamp":1311133656000},"page":"1286-1294","source":"Crossref","is-referenced-by-count":55,"title":["Simplified Newborn Screening Protocol for Lysosomal Storage Disorders"],"prefix":"10.1093","volume":"57","author":[{"given":"Thomas F","family":"Metz","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine and"},{"name":"Research Core Unit of Pediatric Biochemistry and Analytics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P","family":"Mechtler","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine and"},{"name":"Research Core Unit of Pediatric Biochemistry and Analytics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J","family":"Orsini","sequence":"first","affiliation":[{"name":"Biggs Laboratory, Wadsworth Center, New York State Department of Health, Albany, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Martin","sequence":"first","affiliation":[{"name":"Biggs Laboratory, Wadsworth Center, New York State Department of Health, Albany, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bori","family":"Shushan","sequence":"first","affiliation":[{"name":"Clinical Mass Spec Consultants, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L","family":"Herman","sequence":"first","affiliation":[{"name":"Thermo Fisher Scientific, 101 Constitution Boulevard, Franklin MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"Ratschmann","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chike B","family":"Item","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine and"},{"name":"Research Core Unit of Pediatric Biochemistry and Analytics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berthold","family":"Streubel","sequence":"first","affiliation":[{"name":"Department of Pathology, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt R","family":"Herkner","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine and"},{"name":"Research Core Unit of Pediatric Biochemistry and Analytics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C","family":"Kasper","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine and"},{"name":"Research Core Unit of Pediatric Biochemistry and Analytics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,9,1]]},"reference":[{"key":"2020022705020859500_B1","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1373\/clinchem.2004.035907","article-title":"Direct multiplex assay of lysosomal enzymes in dried blood spots for newborn screening","volume":"50","author":"Li","year":"2004","journal-title":"Clin Chem"},{"issue":"12","key":"2020022705020859500_B2","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1373\/clinchem.2010.152009","article-title":"A tandem mass spectrometry triplex assay for the detection of Fabry, Pompe, and mucopolysaccharidosis-I (Hurler)","volume":"56","author":"Duffey","year":"2010","journal-title":"Clin Chem"},{"key":"2020022705020859500_B3","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1373\/clinchem.2008.104711","article-title":"Multiplex enzyme assay screening of dried blood spots for lysosomal storage disorders by using tandem mass spectrometry","volume":"54","author":"Zhang","year":"2008","journal-title":"Clin Chem"},{"key":"2020022705020859500_B4","doi-asserted-by":"crossref","first-page":"9587","DOI":"10.1021\/ac102090v","article-title":"Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: application to screening newborns for mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)","volume":"82","author":"Duffey","year":"2010","journal-title":"Anal Chem"},{"issue":"1","key":"2020022705020859500_B5","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1373\/clinchem.2010.149880","article-title":"Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: application to screening newborns for mucopolysaccharidosis IVA","volume":"57","author":"Khaliq","year":"2010","journal-title":"Clin Chem"},{"key":"2020022705020859500_B6","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1373\/clinchem.2004.047167","article-title":"Tandem mass spectrometric analysis of dried blood spots for screening of mucopolysaccharidosis I in newborns","volume":"51","author":"Wang","year":"2005","journal-title":"Clin Chem"},{"key":"2020022705020859500_B7","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1373\/clinchem.2006.077263","article-title":"Tandem mass spectrometry for the direct assay of enzymes in dried blood spots: application to newborn screening for mucopolysaccharidosis II (Hunter disease)","volume":"53","author":"Wang","year":"2007","journal-title":"Clin Chem"},{"key":"2020022705020859500_B8","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1542\/peds.2007-2222","article-title":"Early detection of Pompe disease by newborn screening is feasible: results from the Taiwan screening program","volume":"122","author":"Chien","year":"2008","journal-title":"Pediatrics"},{"key":"2020022705020859500_B9","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.clinbiochem.2009.01.022","article-title":"Implementation of newborn screening for Krabbe disease: population study and cutoff determination","volume":"42","author":"Orsini","year":"2009","journal-title":"Clin Biochem"},{"issue":"1","key":"2020022705020859500_B10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jpeds.2011.02.026","article-title":"Newborn bloodspot screening for lysosomal storage disorders","volume":"159","author":"Zhou","year":"2011","journal-title":"J Pediatr"},{"key":"2020022705020859500_B11","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1016\/j.cca.2010.03.009","article-title":"Newborn screening for Fabry disease by measuring GLA activity using tandem mass spectrometry","volume":"411","author":"Dajnoki","year":"2010","journal-title":"Clin Chim Acta"},{"key":"2020022705020859500_B12","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1373\/clinchem.2008.107722","article-title":"Newborn screening for Pompe disease by measuring acid alpha-glucosidase activity using tandem mass spectrometry","volume":"54","author":"Dajnoki","year":"2008","journal-title":"Clin Chem"},{"key":"2020022705020859500_B13","article-title":"Analysis of glucocerebrosidase activity in dry blood spots using tandem mass spectrometry","author":"Legini","year":"2010","journal-title":"Clin Chim Acta"},{"key":"2020022705020859500_B14","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1373\/clinchem.2009.127522","article-title":"Mass spectrometry in the clinical laboratory: how have we done, and where do we need to be?","volume":"55","author":"Annesley","year":"2009","journal-title":"Clin Chem"},{"key":"2020022705020859500_B15","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1002\/mas.20295","article-title":"A review of clinical diagnostic applications of liquid chromatography-tandem mass spectrometry","volume":"29","author":"Shushan","year":"2010","journal-title":"Mass Spectrom Rev"},{"key":"2020022705020859500_B16","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1373\/clinchem.2003.028381","article-title":"Tandem mass spectrometry for the direct assay of enzymes in dried blood spots: application to newborn screening for Krabbe disease","volume":"50","author":"Li","year":"2004","journal-title":"Clin Chem"},{"key":"2020022705020859500_B17","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1002\/rcm.784","article-title":"Generic serial and parallel on-line direct-injection using turbulent flow liquid chromatography\/tandem mass spectrometry","volume":"16","author":"Grant","year":"2002","journal-title":"Rapid Commun Mass Spectrom"},{"key":"2020022705020859500_B18","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1002\/rcm.4496","article-title":"The application of multiplexed, multi-dimensional ultra-high-performance liquid chromatography\/tandem mass spectrometry to the high-throughput screening of lysosomal storage disorders in newborn dried bloodspots","volume":"24","author":"Kasper","year":"2010","journal-title":"Rapid Commun Mass Spectrom"},{"key":"2020022705020859500_B19","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s00508-010-1457-3","article-title":"The National Austrian Newborn Screening Program: eight years experience with mass spectrometry","volume":"122","author":"Kasper","year":"2010","journal-title":"Past, present, and future goals. Wien Klin Wochenschr"},{"key":"2020022705020859500_B20","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1373\/clinchem.2008.115410","article-title":"Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: application to screening newborns for mucopolysaccharidosis I","volume":"54","author":"Blanchard","year":"2008","journal-title":"Clin Chem"},{"key":"2020022705020859500_B21","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1001\/jama.281.3.249","article-title":"Prevalence of lysosomal storage disorders","volume":"281","author":"Meikle","year":"1999","journal-title":"JAMA"},{"key":"2020022705020859500_B22","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1001\/archneur.60.3.322","article-title":"Insights into the diagnosis and treatment of lysosomal storage diseases","volume":"60","author":"Wenger","year":"2003","journal-title":"Arch Neurol"},{"key":"2020022705020859500_B23","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/iub.284","article-title":"Therapy for lysosomal storage disorders","volume":"62","author":"Beck","year":"2010","journal-title":"IUBMB Life"},{"key":"2020022705020859500_B24","doi-asserted-by":"crossref","first-page":"6113","DOI":"10.1021\/ac900504s","article-title":"New strategy for the screening of lysosomal storage disorders: the use of the online trapping-and-cleanup liquid chromatography\/mass spectrometry","volume":"81","author":"la Marca","year":"2009","journal-title":"Anal Chem"},{"key":"2020022705020859500_B25","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1373\/clinchem.2008.111864","article-title":"Development and evaluation of quality control dried blood spot materials in newborn screening for lysosomal storage disorders","volume":"55","author":"De Jesus","year":"2009","journal-title":"Clin Chem"},{"key":"2020022705020859500_B26","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1097\/GIM.0b013e31820d5e67","article-title":"Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project","volume":"13","author":"McHugh","year":"2011","journal-title":"Genet Med"},{"key":"2020022705020859500_B27","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.cca.2009.11.027","article-title":"Rapid and accurate denaturating high performance liquid chromatography protocol for the detection of alpha-l-iduronidase mutations causing mucopolysaccharidosis type I","volume":"411","author":"Kasper","year":"2010","journal-title":"Clin Chim Acta"},{"key":"2020022705020859500_B28","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1053\/j.semperi.2009.12.008","article-title":"Digital microfluidics: a future technology in the newborn screening laboratory?","volume":"34","author":"Millington","year":"2010","journal-title":"Semin Perinatol"},{"key":"2020022705020859500_B29","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.pediatrneurol.2008.11.010","article-title":"Newborn screening for Krabbe disease: the New York State model","volume":"40","author":"Duffner","year":"2009","journal-title":"Pediatr Neurol"},{"key":"2020022705020859500_B30","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1056\/NEJMoa042604","article-title":"Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease","volume":"352","author":"Escolar","year":"2005","journal-title":"N Engl J Med"},{"key":"2020022705020859500_B31","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1373\/clinchem.2009.131300","article-title":"National Academy of Clinical Biochemistry laboratory medicine practice guidelines: follow-up testing for metabolic disease identified by expanded newborn screening using tandem mass spectrometry; executive summary","volume":"55","author":"Dietzen","year":"2009","journal-title":"Clin Chem"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/57\/9\/1286\/32656151\/clinchem1286.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/57\/9\/1286\/32656151\/clinchem1286.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T21:48:19Z","timestamp":1712612899000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/57\/9\/1286\/5620999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9,1]]},"references-count":31,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2011,9,1]]},"published-print":{"date-parts":[[2011,9,1]]}},"URL":"https:\/\/doi.org\/10.1373\/clinchem.2011.164640","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,9,1]]},"published":{"date-parts":[[2011,9,1]]}}}