Two-Tiered Newborn Screening with Post-Analytical Tools for Pompe Disease and Mucopolysaccharidosis Type I Results in Performance Improvement and Future Direction
Open Access
- 14 January 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Neonatal Screening
- Vol. 6 (1), 2
- https://doi.org/10.3390/ijns6010002
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.Keywords
Funding Information
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HHSN275201400017C, HSN275201500001I)
This publication has 19 references indexed in Scilit:
- Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass SpectrometryMolecular Genetics and Metabolism, 2016
- Tandem Mass Spectrometry Has a Larger Analytical Range than Fluorescence Assays of Lysosomal Enzymes: Application to Newborn Screening and Diagnosis of Mucopolysaccharidoses Types II, IVA, and VIClinical Chemistry, 2015
- Long-Term Prognosis of Patients with Infantile-Onset Pompe Disease Diagnosed by Newborn Screening and Treated since BirthThe Journal of Pediatrics, 2015
- Lysosomal Storage Disorder Screening Implementation: Findings from the First Six Months of Full Population Pilot Testing in MissouriThe Journal of Pediatrics, 2015
- Postanalytical tools improve performance of newborn screening by tandem mass spectrometryGenetics in Medicine, 2014
- Update of the pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variantsHuman Mutation, 2012
- Predicting cross‐reactive immunological material (CRIM) status in Pompe disease using GAA mutations: Lessons learned from 10 years of clinical laboratory testing experienceSeminars in Medical Genetics, Part C of the American Journal of Medical Genetics, 2012
- Reduction of the false‐positive rate in newborn screening by implementation of MS/MS‐based second‐tier tests: The Mayo Clinic experience (2004–2007)Journal of Inherited Metabolic Disease, 2007
- Molecular genetic defect underlying alpha-L-iduronidase pseudodeficiency.1996
- Pseudodeficiency of α‐iduronidaseJournal of Inherited Metabolic Disease, 1993