TY - JOUR
T1 - Precision newborn screening for lysosomal disorders
AU - Minter Baerg, Melissa M.
AU - Stoway, Stephanie D.
AU - Hart, Jeremy
AU - Mott, Lea
AU - Peck, Dawn S.
AU - Nett, Stephanie L.
AU - Eckerman, Jason S.
AU - Lacey, Jean M.
AU - Turgeon, Coleman T.
AU - Gavrilov, Dimitar
AU - Oglesbee, Devin
AU - Raymond, Kimiyo
AU - Tortorelli, Silvia
AU - Matern, Dietrich
AU - Mørkrid, Lars
AU - Rinaldo, Piero
N1 - Publisher Copyright:
© 2018, American College of Medical Genetics and Genomics.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Purpose: The implementation of newborn screening for lysosomal disorders has uncovered overall poor specificity, psychosocial harm experienced by caregivers, and costly follow-up testing of false-positive cases. We report an informatics solution proven to minimize these issues. Methods: The Kentucky Department for Public Health outsourced testing for mucopolysaccharidosis type I (MPS I) and Pompe disease, conditions recently added to the recommended uniform screening panel, plus Krabbe disease, which was added by legislative mandate. A total of 55,161 specimens were collected from infants born over 1 year starting from February 2016. Testing by tandem mass spectrometry was integrated with multivariate pattern recognition software (Collaborative Laboratory Integrated Reports), which is freely available to newborn screening programs for selection of cases for which a biochemical second-tier test is needed. Results: Of five presumptive positive cases, one was affected with infantile Krabbe disease, two with Pompe disease, and one with MPS I. The remaining case was a heterozygote for the latter condition. The false-positive rate was 0.0018% and the positive predictive value was 80%. Conclusion: Postanalytical interpretive tools can drastically reduce false-positive outcomes, with preliminary evidence of no greater risk of false-negative events, still to be verified by long-term surveillance.
AB - Purpose: The implementation of newborn screening for lysosomal disorders has uncovered overall poor specificity, psychosocial harm experienced by caregivers, and costly follow-up testing of false-positive cases. We report an informatics solution proven to minimize these issues. Methods: The Kentucky Department for Public Health outsourced testing for mucopolysaccharidosis type I (MPS I) and Pompe disease, conditions recently added to the recommended uniform screening panel, plus Krabbe disease, which was added by legislative mandate. A total of 55,161 specimens were collected from infants born over 1 year starting from February 2016. Testing by tandem mass spectrometry was integrated with multivariate pattern recognition software (Collaborative Laboratory Integrated Reports), which is freely available to newborn screening programs for selection of cases for which a biochemical second-tier test is needed. Results: Of five presumptive positive cases, one was affected with infantile Krabbe disease, two with Pompe disease, and one with MPS I. The remaining case was a heterozygote for the latter condition. The false-positive rate was 0.0018% and the positive predictive value was 80%. Conclusion: Postanalytical interpretive tools can drastically reduce false-positive outcomes, with preliminary evidence of no greater risk of false-negative events, still to be verified by long-term surveillance.
KW - Krabbe disease
KW - Pompe
KW - collaborative laboratory integrated report
KW - disease
KW - mucopolysaccharidosis type I
KW - newborn screening
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U2 - 10.1038/gim.2017.194
DO - 10.1038/gim.2017.194
M3 - Article
C2 - 29120458
AN - SCOPUS:85041481866
SN - 1098-3600
VL - 20
SP - 847
EP - 854
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 8
ER -