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.
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.
Authors: Fernanda Bender; Maira G Burin; Kristiane M Tirelli; Fernanda Medeiros; Fernanda Hendges de Bitencourt; Gabriel Civallero; Francyne Kubaski; Heydy Bravo; Antoine Daher; Vanessa Carnier; José F S Franco; Roberto Giugliani Journal: Genet Mol Biol Date: 2020-05-29 Impact factor: 1.771
Authors: Dawn S Peck; Jean M Lacey; Amy L White; Gisele Pino; April L Studinski; Rachel Fisher; Ayesha Ahmad; Linda Spencer; Sarah Viall; Natalie Shallow; Amy Siemon; J Austin Hamm; Brianna K Murray; Kelly L Jones; Dimitar Gavrilov; Devin Oglesbee; Kimiyo Raymond; Dietrich Matern; Piero Rinaldo; Silvia Tortorelli Journal: Int J Neonatal Screen Date: 2020-02-07
Authors: Lene Sörensen; Ulrika von Döbeln; Henrik Åhlman; Annika Ohlsson; Martin Engvall; Karin Naess; Carolina Backman-Johansson; Yvonne Nordqvist; Anna Wedell; Rolf H Zetterström Journal: Int J Neonatal Screen Date: 2020-05-27
Authors: Melissa Leija-Salazar; Fritz J Sedlazeck; Marco Toffoli; Stephen Mullin; Katya Mokretar; Maria Athanasopoulou; Aimee Donald; Reena Sharma; Derralynn Hughes; Anthony H V Schapira; Christos Proukakis Journal: Mol Genet Genomic Med Date: 2019-01-13 Impact factor: 2.183
Authors: Jennifer M Kwon; Dietrich Matern; Joanne Kurtzberg; Lawrence Wrabetz; Michael H Gelb; David A Wenger; Can Ficicioglu; Amy T Waldman; Barbara K Burton; Patrick V Hopkins; Joseph J Orsini Journal: Orphanet J Rare Dis Date: 2018-02-01 Impact factor: 4.123