Two-Tiered Newborn Screening with Post-Analytical Tools for Pompe Disease and Mucopolysaccharidosis Type I Results in Performance Improvement and Future Direction

• Type of Material: Article
• Authors: Patricia Hall, Emory University; Rossana Sanchez Russo, Emory University; Arthur F. Hagar, Georgia Department of Public Health; S. Caleb Jerris, EGL Genetics; Angela Wittenauer, Emory University; William Wilcox, Emory University
• Language: English
• Date: 2020-01-14
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/ijns6010002
• Title of Journal or Parent Work: International Journal of Neonatal Screening
• Volume: 6
• Issue: 1
• Grant/Funding Information: These projects were funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, contract #HHSN275201400017C (Pompe disease) and HSN275201500001I, task order HHSN27500001 (Mucopolysaccharidosis type I).
• Keywords: newborn screening; mucopolysaccharidosis type I; Pompe disease; pseudodeficiency; post-analytical tools
• Research Categories: Biology, Virology

Abstract

We conducted a pilot newborn screening (NBS) study for Pompe disease (PD) and mucopolysaccharidosis type I (MPS I) in the multiethnic population of Georgia. We screened 59,332 infants using a two-tier strategy of flow injection tandem mass spectrometry (FIA-MSMS) enzyme assays. The first tier of testing was a 2-plex assay measuring PD and MPS I enzyme activity, followed by a second-tier test with additional enzymes to improve specificity. Interpretation of results was performed using post-analytical tools created using Collaborative Laboratory Integrated Reports (CLIR). We identified a single case of infantile onset PD, two cases of late onset PD, and one pseudodeficiency. The positive predictive value (PPV) for PD screening during the study was 66.7%. No cases of MPS I were identified during the study period, but there were 2 confirmed cases of pseudodeficiency and 6 cases lost to follow up. The two-tier screening strategy was successful in reducing false positive results and allowed for the identification and early treatment of a case of infantile PD but the frequency of pseudodeficiency in MPS I is problematic. Molecular testing is required and should be covered by the screening program to avoid delays in case resolution.