Newborn Screening for Krabbe Disease: Status Quo and Recommendations for Improvements
Abstract
:1. Introduction
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- Infantile Krabbe disease (IKD), which represents the phenotype described by Knud Krabbe, is characterized clinically by onset of irreversible and rapidly progressive symptoms (inconsolable crying, irritability, spasticity of lower extremities, fisting, vision loss, feeding difficulties) before 12 months of age leading to death before the age of 2 years;
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- Late Infantile Krabbe disease (LIKD) with onset of irreversible and progressive symptoms (loss of milestones, gait changes, hemi- or diplegia, vision loss, febrile seizures, tremors) between 1 to 3 years leading to death within several years;
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- Juvenile Krabbe disease (JKD) with onset of progressive symptoms between 4–17 years of age; and
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- Adult Krabbe disease (AKD) with onset of progressive symptoms at 18 or more years of age.
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Appendix A. False Positive Cases for IKD in Missouri (MO)
References
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State | GA | IL | IL | KY | MO | NY | PA | TN |
---|---|---|---|---|---|---|---|---|
Time Period | 9/2021–6/2023 | 12/2017–10/2021 | 10/2021–9/2023 | 2/2016–6/2023 | 4/2020–5/2023 | 1/2021–6/2023 | 5/2021–5/2023 | 7/2020–5/2023 |
# of Births | 219,399 * | 604,000 | 244,000 | 404,626 | 215,585 | 517,514 | 257,170 | 268,719 |
# of PSY Tests (% of total screened) | 50 (0.02%) | 394 (0.07%) | 206 (0.08%) | 128 (0.03%) | 336 (0.15%) | 37 (0.01%) | 44 (0.02%) | 17 (0.01%) |
PSY Cutoff | 2 nM | 1.08 nM | 1.5 nM | 2 nM | 2 nM | 2 nM | 1.5 nM | 1.5 nM |
IKD | 1 ^ | 5 ^ | 0 | 2 | 1 | 0 | 1 | 1 |
LIKD | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 |
LOKD | 0 | 7 ⁋ | 5 ⁋ | 0 | 1 $ | 1 ⁋ | 2 ⁋ | 3 |
False Positive Cases | 0 | 382 | 35 | 0 | 19 # | 36 | 38 | 13 |
Sensitivity | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% |
Specificity | 100% | 99.94% | 99.99% | 100% | 99.99% | 99.99% | 99.99% | 99.99% |
FPR | 0% | 0.063% | 0.014% | 0% | 0.009% | 0.007% | 0.015% | 0.005% |
PPV | 100% | 3.1% | 12.5% | 100% | 9.5% | 2.7% | 13.6% | 23.5% |
Prevalence | 1:219,399 (0.0005%) | 1:50,333 (0.002%) | 1:48,800 (0.002%) | 1:202,313 (0.0005%) | 1:107793 (0.0009%) | 1:517,514 (0.0002%) | 1:42,862 (0.0023%) | 1:67,180 (0.0015%) |
PPV (prevalence) | 100% | 3.1% | 12.5% | 100% | 9.5% | 2.7% | 13.6% | 23.5% |
PSY Cutoff | GA | IL | KY | MO | NY | PA | TN | Total | |
---|---|---|---|---|---|---|---|---|---|
Time Period | 9/2021–6/2023 | 12/2017–9/2023 | 2/2016–6/2023 | 4/2020–5/2023 | 1/2021–6/2023 | 5/2021–5/2023 | 7/2020–5/2023 | ||
# of Births | - | 219,399 * | 848,000 | 404,626 | 215,585 | 517,514 | 257,170 | 268,719 | 2,731,013 |
True Positive Cases | ≥10 nM | 1 IKD ^ | 5 IKD ^ | 2 IKD | 1 IKD | 0 | 1 IKD | 1 IKD | 11 IKD ^ |
≥5 nM | 1 IKD ^ | 5 IKD ^, 2 LOKD ⁋ | 2 IKD | 1 IKD | 0 | 1 IKD, 1 LIKD | 1 IKD | 11 IKD ^, 1 LIKD, 2 LOKD | |
≥2 nM | 1 IKD ^ | 5 IKD ^, 12 LOKD ⁋ | 2 IKD | 1 IKD | 1 LOKD ⁋ | 1 IKD, 3 LIKD 2 LOKD ⁋ | 1 IKD, 3 LOKD ⁋ | 11 IKD ^, 3 LIKD, 18 LOKD ⁋ | |
False Positive Cases | ≥10 nM | 0 | 0 | 0 | 2 # | 0 | 0 | 0 | 2 # |
≥5 nM | 0 | 0 | 0 | 2 # | 0 | 0 | 0 | 2 # | |
≥2 nM | 0 | 45 | 0 | 2 # | 0 | 0 | 1 | 48 # | |
FPR | ≥10 nM | 0% | 0% | 0% | 0.001% | 0% | 0% | 0% | 0.0001% |
≥5 nM | 0% | 0% | 0% | 0.001% | 0% | 0% | 0% | 0.0001% | |
≥2 nM | 0% | 0.005% | 0% | 0.001% | 0% | 0% | 0.0004% | 0.002% | |
Prevalence | All KD | 1:219,399 | 1:49,882 | 1:202,313 | 1:215,585 | 1:517,514 | 1:42,862 | 1:67,180 | 1:85,344 |
IKD | 1:219,399 | 1:169,600 | 1:202,313 | 1:215,585 | - | 1:257,170 | 1:268,719 | 1:248,274 | |
LIKD | - | - | - | - | - | 1:85,723 | - | 1:910,338 |
State | GA | IL | KY | MO | NY | PA | TN | |
---|---|---|---|---|---|---|---|---|
IKD Cases | HSCT | - | 4 * | 2 * | 1 * | - | 1 * | 1 ^ |
HSCT declined | 1 % | 1 # | - | - | - | - | - | |
LIKD Cases | HSCT | - | - | - | - | - | 2 * | - |
HSCT declined | - | - | - | - | - | - | - | |
Monitored | - | - | - | - | - | 1 ⁋ | - | |
LOKD Cases | HSCT | - | - | - | - | - | - | - |
HSCT declined | - | - | - | - | - | - | - | |
Monitored | - | 12 ⁋ | - | 1 ⁋ | 1 ⁋ | 2 ⁋ | 3 ⁋ |
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Matern, D.; Basheeruddin, K.; Klug, T.L.; McKee, G.; Edge, P.U.; Hall, P.L.; Kurtzberg, J.; Orsini, J.J. Newborn Screening for Krabbe Disease: Status Quo and Recommendations for Improvements. Int. J. Neonatal Screen. 2024, 10, 10. https://doi.org/10.3390/ijns10010010
Matern D, Basheeruddin K, Klug TL, McKee G, Edge PU, Hall PL, Kurtzberg J, Orsini JJ. Newborn Screening for Krabbe Disease: Status Quo and Recommendations for Improvements. International Journal of Neonatal Screening. 2024; 10(1):10. https://doi.org/10.3390/ijns10010010
Chicago/Turabian StyleMatern, Dietrich, Khaja Basheeruddin, Tracy L. Klug, Gwendolyn McKee, Patricia U. Edge, Patricia L. Hall, Joanne Kurtzberg, and Joseph J. Orsini. 2024. "Newborn Screening for Krabbe Disease: Status Quo and Recommendations for Improvements" International Journal of Neonatal Screening 10, no. 1: 10. https://doi.org/10.3390/ijns10010010