Newborn Screening for Krabbe Disease: Status Quo and Recommendations for Improvements

Dietrich Matern; Khaja Basheeruddin; Tracy L Klug; Gwendolyn McKee; Patricia U Edge; Patricia L Hall; Joanne Kurtzberg; Joseph J Orsini

doi:10.3390/ijns10010010

Newborn Screening for Krabbe Disease: Status Quo and Recommendations for Improvements

Int J Neonatal Screen. 2024 Jan 28;10(1):10. doi: 10.3390/ijns10010010.

Authors

Dietrich Matern¹, Khaja Basheeruddin², Tracy L Klug³, Gwendolyn McKee⁴, Patricia U Edge⁵, Patricia L Hall¹, Joanne Kurtzberg⁶, Joseph J Orsini⁷

Affiliations

¹ Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
² Illinois Department of Public Health, Chicago, IL 60612, USA.
³ Missouri State Public Health Laboratory, Jefferson City, MO 65101, USA.
⁴ Tennessee Department of Health, Division of Laboratory Services, Nashville, TN 37243, USA.
⁵ Pennsylvania Department of Health, Harrisburg, PA 17120, USA.
⁶ Department of Pediatrics, Duke University Medical Center, Durham, NC 27705, USA.
⁷ Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA.

Abstract

Krabbe disease (KD) is part of newborn screening (NBS) in 11 states with at least one additional state preparing to screen. In July 2021, KD was re-nominated for addition to the federal Recommended Uniform Screening Panel (RUSP) in the USA with a two-tiered strategy based on psychosine (PSY) as the determinant if an NBS result is positive or negative after a first-tier test revealed decreased galactocerebrosidase activity. Nine states currently screening for KD include PSY analysis in their screening strategy. However, the nomination was rejected in February 2023 because of perceived concerns about a high false positive rate, potential harm to newborns with an uncertain prognosis, and inadequate data on presymptomatic treatment benefit or harm. To address the concern about false positive NBS results, a survey was conducted of the eight NBS programs that use PSY and have been screening for KD for at least 1 year. Seven of eight states responded. We found that: (1) the use of PSY is variable; (2) when modeling the data based on the recommended screening strategy for KD, and applying different cutoffs for PSY, each state could virtually eliminate false positive results without major impact on sensitivity; (3) the reason for the diverse strategies appears to be primarily the difficulty of state programs to adjust screening algorithms due to the concern of possibly missing even an adult-onset case following a change that focuses on infantile and early infantile KD. Contracts with outside vendors and the effort/cost of making changes to a program's information systems can be additional obstacles. We recommend that programs review their historical NBS outcomes for KD with their advisory committees and make transparent decisions on whether to accept false positive results for such a devastating condition or to adjust their procedures to ensure an efficient, effective, and manageable NBS program for KD.

Keywords: Krabbe disease; false positive rate; galactocerebrosidase; globoid cell leukodystrophy; hematopoietic stem cell transplant; newborn screening; psychosine.

Grants and funding

This research received no external funding.