Journal Article

Precision newborn screening for lysosomal disorders

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

2018

Overview

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.

• Publisher: Nature Publishing Group US,Elsevier Limited
• Subject: Biomedical and Life Sciences / Biomedicine / Dried Blood Spot Testing / Female / Glycogen Storage Disease Type II - diagnosis / Human Genetics / Humans / Infant / Infant, Newborn / Laboratory Medicine / Leukodystrophy, Globoid Cell - diagnosis / Lysosomal Storage Diseases - diagnosis / Male / Medical screening / Mucopolysaccharidosis I - diagnosis / Neonatal Screening - methods / Pattern Recognition, Automated / Sensitivity and Specificity / Software / Tandem Mass Spectrometry - methods