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Precision newborn screening for lysosomal disorders
Melissa M Minter Baerg1, Stephanie D Stoway1, Jeremy Hart2,3
1Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Insights
New informatics tools significantly improved newborn screening accuracy for lysosomal disorders, reducing false positives and associated caregiver stress. This enhances early detection of critical conditions like Krabbe disease, Pompe disease, and MPS I.
Area of Science:
- Biochemistry
- Informatics
- Genetics
Background:
- Newborn screening for lysosomal disorders faces challenges with poor specificity and high costs.
- False-positive results cause significant psychosocial harm to caregivers and necessitate expensive follow-up testing.
Purpose of the Study:
- To report an informatics solution to minimize false positives and improve specificity in newborn screening for lysosomal disorders.
- To reduce psychosocial harm and financial burden associated with inaccurate screening results.
Main Methods:
- Implemented multivariate pattern recognition software (Collaborative Laboratory Integrated Reports) integrated with tandem mass spectrometry.
- Collected and analyzed 55,161 infant specimens for mucopolysaccharidosis type I (MPS I), Pompe disease, and Krabbe disease.
Main Results:
- Achieved a false-positive rate of 0.0018% and a positive predictive value of 80%.
- Accurately identified affected infants with Krabbe disease, Pompe disease, and MPS I, distinguishing from heterozygotes.
Conclusions:
- Postanalytical interpretive tools are effective in drastically reducing false-positive outcomes in newborn screening.
- Preliminary evidence suggests no increased risk of false-negative events, warranting long-term surveillance.
Purpose:
The implementation of newborn screening for lysosomal disorders has uncovered overall poor specificity, psychosocial harm experienced by caregivers, and costly follow-up testing of false-positive cases. We report an informatics solution proven to minimize these issues.
Methods:
The Kentucky Department for Public Health outsourced testing for mucopolysaccharidosis type I (MPS I) and Pompe disease, conditions recently added to the recommended uniform screening panel, plus Krabbe disease, which was added by legislative mandate. A total of 55,161 specimens were collected from infants born over 1 year starting from February 2016. Testing by tandem mass spectrometry was integrated with multivariate pattern recognition software (Collaborative Laboratory Integrated Reports), which is freely available to newborn screening programs for selection of cases for which a biochemical second-tier test is needed.
Results:
Of five presumptive positive cases, one was affected with infantile Krabbe disease, two with Pompe disease, and one with MPS I. The remaining case was a heterozygote for the latter condition. The false-positive rate was 0.0018% and the positive predictive value was 80%.
Conclusion:
Postanalytical interpretive tools can drastically reduce false-positive outcomes, with preliminary evidence of no greater risk of false-negative events, still to be verified by long-term surveillance.
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