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Two-Tiered Newborn Screening with Post-Analytical Tools for Pompe Disease and Mucopolysaccharidosis Type I Results in
Patricia L Hall1, Rossana Sanchez1, Arthur F Hagar2
1Department of Human Genetics, Emory University, Atlanta, GA 30322, USA.
Insights
This pilot newborn screening study for Pompe disease (PD) and mucopolysaccharidosis type I (MPS I) in Georgia identified one infantile PD case. A two-tier strategy reduced false positives, but pseudodeficiency warrants further investigation.
Area of Science:
- Medical Genetics
- Biochemistry
- Public Health
Background:
- Newborn screening (NBS) programs aim for early detection of genetic disorders.
- Pompe disease (PD) and mucopolysaccharidosis type I (MPS I) are rare genetic conditions treatable with early intervention.
- Georgia's multiethnic population provided a diverse cohort for this pilot NBS study.
Purpose of the Study:
- To evaluate a two-tier screening strategy for PD and MPS I in newborns.
- To determine the feasibility and effectiveness of implementing these newborn screenings in a large, multiethnic population.
- To assess the positive predictive value (PPV) and identify challenges in the screening process.
Main Methods:
- A pilot NBS study screened 59,332 infants in Georgia.
- A two-tier strategy using flow injection tandem mass spectrometry (FIA-MSMS) enzyme assays was employed.
- Post-analytical tools from Collaborative Laboratory Integrated Reports (CLIR) aided result interpretation.
Main Results:
- One case of infantile-onset PD and two cases of late-onset PD were identified.
- The PPV for PD screening was 66.7%.
- No MPS I cases were found, but two pseudodeficiency cases and six losses to follow-up occurred.
Conclusions:
- The two-tier screening strategy effectively reduced false positives and enabled early PD diagnosis and treatment.
- The high frequency of pseudodeficiency in MPS I screening presents a challenge.
- Integrating molecular testing into the screening program is crucial for timely case resolution.
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.
