Mucopolysaccharidosis type I newborn screening: Importance of second tier testing for ethnically diverse populations

Area of Science:

• Medical Genetics
• Public Health
• Biochemistry

Background:

• Mucopolysaccharidosis type I (MPS I), also known as Hurler syndrome, was added to the Recommended Uniform Screening Panel (RUSP) in 2016.
• Increased implementation of MPS I newborn screening has led to a rise in false positive results.
• Pseudodeficiency alleles, common in individuals of African descent, can cause falsely decreased enzyme activity, contributing to false positives.

Purpose of the Study:

• To describe the experience with MPS I newborn screening in the District of Columbia (DC) from December 2017 to February 2019.
• To review literature on newborn screening and family experiences related to MPS I.
• To propose solutions for improving MPS I newborn screening programs and addressing identified concerns.

Main Methods:

• Retrospective review of MPS I newborn screening data from the District of Columbia.
• Literature review on newborn screening for MPS I and associated challenges.
• Analysis of factors contributing to false positive screening results, including pseudodeficiency alleles.

Main Results:

• The DC experience highlighted challenges with MPS I newborn screening, including a notable rate of false positives.
• Pseudodeficiency alleles were identified as a significant factor in false positive results, disproportionately affecting minority populations.
• Overrepresentation of screen positives in minority groups raises concerns about health disparities and community trust.

Conclusions:

• Improving MPS I newborn screening requires addressing the impact of pseudodeficiency alleles and their higher prevalence in certain populations.
• Strategies must be developed to mitigate health disparities and build community trust in genetic screening programs.
• Consideration of these factors is essential for enhancing the effectiveness and equity of newborn screening programs nationally and internationally.