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PMID: 21325949 Published · ppublish English Journal Article Multicenter Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Validation Study

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

McHugh D, Cameron CA, Abdenur JE, Abdulrahman M, Adair O, Al Nuaimi SA, Åhlman H, Allen JJ, Antonozzi I, Archer S, Au S, Auray-Blais C, Baker M, Bamforth F, Beckmann K, Pino GB, Berberich SL, Binard R, Boemer F, Bonham J, Breen NN, Bryant SC, Caggana M, Caldwell SG, Camilot M, Campbell C, Carducci C, Bryant SC, Caggana M, Caldwell SG, Camilot M, Campbell C, Carducci C, Cariappa R, Carlisle C, Caruso U, Cassanello M, Castilla AM, Ramos DE, Chakraborty P, Chandrasekar R, Ramos AC, Cheillan D, Chien YH, Childs TA, Chrastina P, Sica YC, de Juan JA, Colandre ME, Espinoza VC, Corso G, Currier R, Cyr D, Czuczy N, D'Apolito O, Davis T, de Sain-Van der Velden MG, Delgado Pecellin C, Di Gangi IM, Di Stefano CM, Dotsikas Y, Downing M, Downs SM, Dy B, Dymerski M, Rueda I, Elvers B, Eaton R, Eckerd BM, El Mougy F, Eroh S, Espada M, Evans C, Fawbush S, Fijolek KF, Fisher L, Franzson L, Frazier DM, Garcia LR, Bermejo MS, Gavrilov D, Gerace R, Giordano G, Irazabal YG, Greed LC, Grier R, Grycki E, Gu X, Gulamali-Majid F, Hagar AF, Han L, Hannon WH, Haslip C, Hassan FA, He M, Hietala A, Himstedt L, Hoffman GL, Hoffman W, Hoggatt P, Hopkins PV, Hougaard DM, Hughes K, Hunt PR, Hwu WL, Hynes J, Ibarra-González I, Ingham CA, Ivanova M, Jacox WB, John C, Johnson JP, Jónsson JJ, Karg E, Kasper D, Klopper B, Katakouzinos D, Khneisser I, Knoll D, Kobayashi H, Koneski R, Kozich V, Kouapei R, Kohlmueller D, Kremensky I, la Marca G, Lavochkin M, Lee SY, Lehotay DC, Lemes A, Lepage J, Lesko B, Lewis B, Lim C, Linard S, Lindner M, Lloyd-Puryear MA, Lorey F, Loukas YL, Luedtke J, Maffitt N, Magee JF, Manning A, Manos S, Marie S, Hadachi SM, Marquardt G, Martin SJ, Matern D, Mayfield Gibson SK, Mayne P, McCallister TD, McCann M, McClure J, McGill JJ, McKeever CD, McNeilly B, Morrissey MA, Moutsatsou P, Mulcahy EA, Nikoloudis D, Norgaard-Pedersen B, Oglesbee D, Oltarzewski M, Ombrone D, Ojodu J, Papakonstantinou V, Reoyo SP, Park HD, Pasquali M, Pasquini E, Patel P, Pass KA, Peterson C, Pettersen RD, Pitt JJ, Poh S, Pollak A, Porter C, Poston PA, Price RW, Queijo C, Quesada J, Randell E, Ranieri E, Raymond K, Reddic JE, Reuben A, Ricciardi C, Rinaldo P, Rivera JD, Roberts A, Rocha H, Roche G, Greenberg CR, Mellado JM, Juan-Fita MJ, Ruiz C, Ruoppolo M, Rutledge SL, Ryu E, Saban C, Sahai I, García-Blanco MI, Santiago-Borrero P, Schenone A, Schoos R, Schweitzer B, Scott P, Seashore MR, Seeterlin MA, Sesser DE, Sevier DW, Shone SM, Sinclair G, Skrinska VA, Stanley EL, Strovel ET, Jones AL, Sunny S, Takats Z, Tanyalcin T, Teofoli F, Thompson JR, Tomashitis K, Domingos MT, Torres J, Torres R, Tortorelli S, Turi S, Turner K, Tzanakos N, Valiente AG, Vallance H, Vela-Amieva M, Vilarinho L, von Döbeln U, Vincent MF, Vorster BC, Watson MS, Webster D, Weiss S, Wilcken B, Wiley V, Williams SK, Willis SA, Woontner M, Wright K, Yahyaoui R, Yamaguchi S, Yssel M, Zakowicz WM

Abstract

To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. 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. 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). 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.

MeSH Terms
Amino Acids/blood Carnitine/analogs & derivatives,blood Humans Infant, Newborn International Cooperation Metabolic Diseases/diagnosis Neonatal Screening Reference Values Sensitivity and Specificity Software Tandem Mass Spectrometry
Chemicals
Amino Acids acylcarnitine Carnitine
Authors & Affiliations
252 authors, click to expand affiliations / ORCID
McHugh David M S
Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Cameron Cynthia A
Abdenur Jose E
Abdulrahman Mahera
Adair Ona
Al Nuaimi Shahira Ahmed
Åhlman Henrik
Allen Jennifer J
Antonozzi Italo
Archer Shaina
Au Sylvia
Auray-Blais Christiane
Baker Mei
Bamforth Fiona
Beckmann Kinga
Pino Gessi Bentz
Berberich Stanton L
Binard Robert
Boemer François
Bonham Jim
Breen Nancy N
Bryant Sandra C
Caggana Michele
Caldwell S Graham
Camilot Marta
Campbell Carlene
Carducci Claudia
Bryant Sandra C
Caggana Michele
Caldwell S Graham
Camilot Marta
Campbell Carlene
Carducci Claudia
Cariappa Rohit
Carlisle Clover
Caruso Ubaldo
Cassanello Michela
Castilla Ane Miren
Ramos Daisy E Castiñeiras
Chakraborty Pranesh
Chandrasekar Ram
Ramos Alfredo Chardon
Cheillan David
Chien Yin-Hsiu
Childs Thomas A
Chrastina Petr
Sica Yuri Cleverthon
de Juan Jose Angel Cocho
Colandre Maria Elena
Espinoza Veronica Cornejo
Corso Gaetano
Currier Robert
Cyr Denis
Czuczy Noemi
D'Apolito Oceania
Davis Tim
de Sain-Van der Velden Monique G
Delgado Pecellin Carmen
Di Gangi Iole Maria
Di Stefano Cristina Maria
Dotsikas Yannis
Downing Melanie
Downs Stephen M
Dy Bonifacio
Dymerski Mark
Rueda Inmaculada
Elvers Bert
Eaton Roger
Eckerd Barbara M
El Mougy Fatma
Eroh Sarah
Espada Mercedes
Evans Catherine
Fawbush Sandy
Fijolek Kristel F
Fisher Lawrence
Franzson Leifur
Frazier Dianne M
Garcia Luciana R C
Bermejo Maria Sierra García-Valdecasas
Gavrilov Dimitar
Gerace Rosemarie
Giordano Giuseppe
Irazabal Yolanda González
Greed Lawrence C
Grier Robert
Grycki Elyse
Gu Xuefan
Gulamali-Majid Fizza
Hagar Arthur F
Han Lianshu
Hannon W Harry
Haslip Christa
Hassan Fayza Abdelhamid
He Miao
Hietala Amy
Himstedt Leslie
Hoffman Gary L
Hoffman William
Hoggatt Philis
Hopkins Patrick V
Hougaard David M
Hughes Kerie
Hunt Patricia R
Hwu Wuh-Liang
Hynes June
Ibarra-González Isabel
Ingham Cindy A
Ivanova Maria
Jacox Ward B
John Catharine
Johnson John P
Jónsson Jón J
Karg Eszter
Kasper David
Klopper Brenda
Katakouzinos Dimitris
Khneisser Issam
Knoll Detlef
Kobayashi Hirinori
Koneski Ronald
Kozich Viktor
Kouapei Rasoul
Kohlmueller Dirk
Kremensky Ivo
la Marca Giancarlo
Lavochkin Marcia
Lee Soo-Youn
Lehotay Denis C
Lemes Aida
Lepage Joyce
Lesko Barbara
Lewis Barry
Lim Carol
Linard Sharon
Lindner Martin
Lloyd-Puryear Michele A
Lorey Fred
Loukas Yannis L
Luedtke Julie
Maffitt Neil
Magee J Fergall
Manning Adrienne
Manos Shawn
Marie Sandrine
Hadachi Sônia Marchezi
Marquardt Gregg
Martin Stephen J
Matern Dietrich
Mayfield Gibson Stephanie K
Mayne Philip
McCallister Tonya D
McCann Mark
McClure Julie
McGill James J
McKeever Christine D
McNeilly Barbara
Morrissey Mark A
Moutsatsou Paraskevi
Mulcahy Eleanor A
Nikoloudis Dimitris
Norgaard-Pedersen Bent
Oglesbee Devin
Oltarzewski Mariusz
Ombrone Daniela
Ojodu Jelili
Papakonstantinou Vagelis
Reoyo Sherly Pardo
Park Hyung-Doo
Pasquali Marzia
Pasquini Elisabetta
Patel Pallavi
Pass Kenneth A
Peterson Colleen
Pettersen Rolf D
Pitt James J
Poh Sherry
Pollak Arnold
Porter Cory
Poston Philip A
Price Ricky W
Queijo Cecilia
Quesada Jonessy
Randell Edward
Ranieri Enzo
Raymond Kimiyo
Reddic John E
Reuben Alejandra
Ricciardi Charla
Rinaldo Piero
Rivera Jeff D
Roberts Alicia
Rocha Hugo
Roche Geraldine
Greenberg Cheryl Rochman
Mellado José María Egea
Juan-Fita María Jesús
Ruiz Consuelo
Ruoppolo Margherita
Rutledge S Lane
Ryu Euijung
Saban Christine
Sahai Inderneel
García-Blanco Maria Isabel Salazar
Santiago-Borrero Pedro
Schenone Andrea
Schoos Roland
Schweitzer Barb
Scott Patricia
Seashore Margretta R
Seeterlin Mary A
Sesser David E
Sevier Darrin W
Shone Scott M
Sinclair Graham
Skrinska Victor A
Stanley Eleanor L
Strovel Erin T
Jones April L Studinski
Sunny Sherlykutty
Takats Zoltan
Tanyalcin Tijen
Teofoli Francesca
Thompson J Robert
Tomashitis Kathy
Domingos Mouseline Torquado
Torres Jasmin
Torres Rosario
Tortorelli Silvia
Turi Sandor
Turner Kimberley
Tzanakos Nick
Valiente Alf G
Vallance Hillary
Vela-Amieva Marcela
Vilarinho Laura
von Döbeln Ulrika
Vincent Marie-Francoise
Vorster B Chris
Watson Michael S
Webster Dianne
Weiss Sheila
Wilcken Bridget
Wiley Veronica
Williams Sharon K
Willis Sharon A
Woontner Michael
Wright Katherine
Yahyaoui Raquel
Yamaguchi Seiji
Yssel Melissa
Zakowicz Wendy M
Article Info
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
Abbr.
Genet Med
ISSN
1530-0366
Published
2011-03-00
Pages
230-54
Language
English
Region
United States
NLM ID
9815831
Subset
IM
Grants
PHS HHS · U22MC03963 · United States
Corrections
CommentIn
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