Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project

David M.S. McHugh, Cynthia A. Cameron, Jose E. Abdenur, Mahera Abdulrahman, Ona Adair, Shahira Ahmed Al Nuaimi, Henrik Åhlman, Jennifer J. Allen, Italo Antonozzi, Shaina Archer, Sylvia Au, Christiane Auray-Blais, Mei Baker, Fiona Bamforth, Kinga Beckmann, Gessi Bentz Pino, Stanton L. Berberich, Robert Binard, François Boemer, Jim BonhamNancy N. Breen, Sandra C. Bryant, Michele Caggana, S. Graham Caldwell, Marta Camilot, Carlene Campbell, Claudia Carducci, Rohit Cariappa, Clover Carlisle, Ubaldo Caruso, Michela Cassanello, Ane Miren Castilla, Daisy E.Castiñeiras Ramos, Pranesh Chakraborty, Ram Chandrasekar, Alfredo Chardon Ramos, David Cheillan, Yin Hsiu Chien, Thomas A. Childs, Petr Chrastina, Yuri Cleverthon Sica, Jose Angel Cocho De Juan, Maria Elena Colandre, Veronica Cornejo Espinoza, Gaetano Corso, Robert Currier, Denis Cyr, Noemi Czuczy, Oceania D'Apolito, Tim Davis, Monique G. De Sain-Van Der Velden, Carmen Delgado Pecellin, Iole Maria Di Gangi, Cristina Maria Di Stefano, Yannis Dotsikas, Melanie Downing, Stephen M. Downs, Bonifacio Dy, Mark Dymerski, Inmaculada Rueda, Bert Elvers, Roger Eaton, Barbara M. Eckerd, Fatma El Mougy, Sarah Eroh, Mercedes Espada, Catherine Evans, Sandy Fawbush, Kristel F. Fijolek, Lawrence Fisher, Leifur Franzson, Dianne M. Frazier, Luciana R.C. Garcia, Maria Sierra García Valdecasas Bermejo, Dimitar Gavrilov, Rosemarie Gerace, Giuseppe Giordano, Yolanda González Irazabal, Lawrence C. Greed, Robert Grier, Elyse Grycki, Xuefan Gu, Fizza Gulamali-Majid, Arthur F. Hagar, Lianshu Han, W. Harry Hannon, Christa Haslip, Fayza Abdelhamid Hassan, Miao He, Amy Hietala, Leslie Himstedt, Gary L. Hoffman, William Hoffman, Philis Hoggatt, Patrick V. Hopkins, David M. Hougaard, Kerie Hughes, Patricia R. Hunt, Wuh Liang Hwu, June Hynes, Isabel Ibarra-González, Cindy A. Ingham, Maria Ivanova, Ward B. Jacox, Catharine John, John P. Johnson, Jón J. Jónsson, Eszter Karg, David Kasper, Brenda Klopper, Dimitris Katakouzinos, Issam Khneisser, Detlef Knoll, Hirinori Kobayashi, Ronald Koneski, Viktor Kožich, Rasoul Kouapei, Dirk Kohlmueller, Ivo Kremensky, Giancarlo La Marca, Marcia Lavochkin, Soo Youn Lee, Denis C. Lehotay, Aida Lemes, Joyce Lepage, Barbara Lesko, Barry Lewis, Carol Lim, Sharon Linard, Martin Lindner, Michele A. Lloyd-Puryear, Fred Lorey, Yannis L. Loukas, Julie Luedtke, Neil Maffitt, J. Fergall Magee, Adrienne Manning, Shawn Manos, Sandrine Marie, Sônia Marchezi Hadachi, Gregg Marquardt, Stephen J. Martin, Dietrich Matern, Stephanie K.Mayfield Gibson, Philip Mayne, Tonya D. McCallister, Mark McCann, Julie McClure, James J. McGill, Christine D. McKeever, Barbara McNeilly, Mark A. Morrissey, Paraskevi Moutsatsou, Eleanor A. Mulcahy, Dimitris Nikoloudis, Bent Norgaard-Pedersen, Devin Oglesbee, Mariusz Oltarzewski, Daniela Ombrone, Jelili Ojodu, Vagelis Papakonstantinou, Sherly Pardo Reoyo, Hyung Doo Park, Marzia Pasquali, Elisabetta Pasquini, Pallavi Patel, Kenneth A. Pass, Colleen Peterson, Rolf D. Pettersen, James J. Pitt, Sherry Poh, Arnold Pollak, Cory Porter, Philip A. Poston, Ricky W. Price, Cecilia Queijo, Jonessy Quesada, Edward Randell, Enzo Ranieri, Kimiyo Raymond, John E. Reddic, Alejandra Reuben, Charla Ricciardi, Piero Rinaldo, Jeff D. Rivera, Alicia Roberts, Hugo Rocha, Geraldine Roche, Cheryl Rochman Greenberg, José María Egea Mellado, María Jesús Juan-Fita, Consuelo Ruiz, Margherita Ruoppolo, S. Lane Rutledge, Euijung Ryu, Christine Saban, Inderneel Sahai, Maria Isabel Salazar García-Blanco, Pedro Santiago-Borrero, Andrea Schenone, Roland Schoos, Barb Schweitzer, Patricia Scott, Margretta R. Seashore, Mary A. Seeterlin, David E. Sesser, Darrin W. Sevier, Scott M. Shone, Graham Sinclair, Victor A. Skrinska, Eleanor L. Stanley, Erin T. Strovel, April L.Studinski Jones, Sherlykutty Sunny, Zoltan Takats, Tijen Tanyalcin, Francesca Teofoli, J. Robert Thompson, Kathy Tomashitis, Mouseline Torquado Domingos, Jasmin Torres, Rosario Torres, Silvia Tortorelli, Sandor Turi, Kimberley Turner, Nick Tzanakos, Alf G. Valiente, Hillary Vallance, Marcela Vela-Amieva, Laura Vilarinho, Ulrika Von Döbeln, Marie Francoise Vincent, B. Chris Vorster, Michael S. Watson, Dianne Webster, Sheila Weiss, Bridget Wilcken, Veronica Wiley, Sharon K. Williams, Sharon A. Willis, Michael Woontner, Katherine Wright, Raquel Yahyaoui, Seiji Yamaguchi, Melissa Yssel, Wendy M. Zakowicz

Research output: Contribution to journalArticle

185 Scopus citations

Abstract

PURPOSE:: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. METHODS:: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration. RESULTS:: As of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341). CONCLUSION:: An unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders.

Original languageEnglish (US)
Pages (from-to)230-254
Number of pages25
JournalGenetics in Medicine
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2011

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Keywords

  • Acylcarnitines
  • amino acids
  • inborn errors of metabolism
  • newborn screening
  • tandem mass spectrometry

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

McHugh, D. M. S., Cameron, C. A., Abdenur, J. E., Abdulrahman, M., Adair, O., Al Nuaimi, S. A., Åhlman, H., Allen, J. J., Antonozzi, I., Archer, S., Au, S., Auray-Blais, C., Baker, M., Bamforth, F., Beckmann, K., Pino, G. B., Berberich, S. L., Binard, R., Boemer, F., ... Zakowicz, W. M. (2011). Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project. Genetics in Medicine, 13(3), 230-254. https://doi.org/10.1097/GIM.0b013e31820d5e67