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

Arthur F. Hagar,S. Caleb Jerris,Patricia L. Hall,William R. Wilcox,Rossana Sanchez,Angela Wittenauer

doi: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.

Highlights

Pompe disease (PD, OMIM #232300) and Mucopolysaccharidosis Type I (MPS I, OMIM #607014) are the first two lysosomal storage disorders to be added to the Recommended Uniform Screening Panel (RUSP) for newborn screening (NBS) in the United States [1]
Post-analytical tools, fixed cutoffs and cutoffs based on the daily mean have all been used
For mucopolysaccharidosis type I (MPS I), the most effective second tier test is likely quantitation of dermatan and heparan sulfate in blood spots, as used in the screening of infants born in Kentucky [1]

Summary

Introduction

Pompe disease (PD, OMIM #232300) and Mucopolysaccharidosis Type I (MPS I, OMIM #607014) are the first two lysosomal storage disorders to be added to the Recommended Uniform Screening Panel (RUSP) for newborn screening (NBS) in the United States [1]. Pompe disease is a progressive, autosomal recessive lysosomal storage disorder primarily affecting skeletal and cardiac muscle. It presents with varying degrees of severity, ranging from an infantile form with cardiomyopathy and weakness before 12 months of life to later onset forms which present primarily with proximal muscle weakness, without cardiomyopathy [2,3]. MPS I is a progressive, autosomal recessive lysosomal storage disorder with multiorgan involvement. Improved outcomes have been reported with early intervention for both disorders [5]

Methods

Results

Conclusion