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dc.contributor.authorKlopper, Brenda
dc.contributor.authorVorster, Barend Christiaan
dc.contributor.authorMcHugh, David M.S.
dc.contributor.authorCameron, Cynthia A.
dc.contributor.authorAbdenur, Jose E.
dc.date.accessioned2012-10-09T07:44:30Z
dc.date.available2012-10-09T07:44:30Z
dc.date.issued2011
dc.identifier.citationMcHugh, D.M.S. et al. 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. [http://www.nature.com/gim/index.html]en_US
dc.identifier.issn1098-3600
dc.identifier.issn1530-0366 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/7457
dc.descriptionOfficial journal of the American College of Medical Genetics and Genomicsen_US
dc.description.abstractPurpose: 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.en_US
dc.description.urihttp://dx.doi.org/10.1097/GIM.0b013e31820d5e67
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.subjectAcylarnitinesen_US
dc.subjectamino acidsen_US
dc.subjectinborn errors of metabolismen_US
dc.subjectnewborn screeningen_US
dc.subjecttandem mass spectrometryen_US
dc.titleClinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative projecten_US
dc.typeArticleen_US


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