Precision newborn screening for lysosomal disorders

Melissa M. Minter Baerg, Stephanie D. Stoway, Jeremy Hart, Lea Mott, Dawn S. Peck, Stephanie L. Nett, Jason S. Eckerman, Jean M. Lacey, Coleman T. Turgeon, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Silvia Tortorelli, Dietrich Matern, Lars Mørkrid, Piero Rinaldo

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)847-854
Number of pages8
JournalGenetics in Medicine
Volume20
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Globoid Cell Leukodystrophy
Glycogen Storage Disease Type II
Newborn Infant
Mucopolysaccharidosis I
Informatics
Heterozygote
Tandem Mass Spectrometry
Caregivers
Software
Public Health

Keywords

  • collaborative laboratory integrated report
  • disease
  • Krabbe disease
  • mucopolysaccharidosis type I
  • newborn screening
  • Pompe

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Minter Baerg, M. M., Stoway, S. D., Hart, J., Mott, L., Peck, D. S., Nett, S. L., ... Rinaldo, P. (2018). Precision newborn screening for lysosomal disorders. Genetics in Medicine, 20(8), 847-854. https://doi.org/10.1038/gim.2017.194

Precision newborn screening for lysosomal disorders. / Minter Baerg, Melissa M.; Stoway, Stephanie D.; Hart, Jeremy; Mott, Lea; Peck, Dawn S.; Nett, Stephanie L.; Eckerman, Jason S.; Lacey, Jean M.; Turgeon, Coleman T.; Gavrilov, Dimitar; Oglesbee, Devin; Raymond, Kimiyo; Tortorelli, Silvia; Matern, Dietrich; Mørkrid, Lars; Rinaldo, Piero.

In: Genetics in Medicine, Vol. 20, No. 8, 01.08.2018, p. 847-854.

Research output: Contribution to journalArticle

Minter Baerg, MM, Stoway, SD, Hart, J, Mott, L, Peck, DS, Nett, SL, Eckerman, JS, Lacey, JM, Turgeon, CT, Gavrilov, D, Oglesbee, D, Raymond, K, Tortorelli, S, Matern, D, Mørkrid, L & Rinaldo, P 2018, 'Precision newborn screening for lysosomal disorders', Genetics in Medicine, vol. 20, no. 8, pp. 847-854. https://doi.org/10.1038/gim.2017.194
Minter Baerg MM, Stoway SD, Hart J, Mott L, Peck DS, Nett SL et al. Precision newborn screening for lysosomal disorders. Genetics in Medicine. 2018 Aug 1;20(8):847-854. https://doi.org/10.1038/gim.2017.194
Minter Baerg, Melissa M. ; Stoway, Stephanie D. ; Hart, Jeremy ; Mott, Lea ; Peck, Dawn S. ; Nett, Stephanie L. ; Eckerman, Jason S. ; Lacey, Jean M. ; Turgeon, Coleman T. ; Gavrilov, Dimitar ; Oglesbee, Devin ; Raymond, Kimiyo ; Tortorelli, Silvia ; Matern, Dietrich ; Mørkrid, Lars ; Rinaldo, Piero. / Precision newborn screening for lysosomal disorders. In: Genetics in Medicine. 2018 ; Vol. 20, No. 8. pp. 847-854.
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