Two-tiered newborn screening for infantile Krabbe disease allows timely treatment initiation and avoids false-positive results
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Patricia L Hall1, Amy L White1, Dawn Peck1
1Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Insights
The two-tier newborn screening (NBS) strategy for Infantile Krabbe disease (IKD) using psychosine (PSY) analysis significantly speeds up diagnosis and treatment initiation, ensuring timely hematopoietic stem cell transplant (HSCT). This approach is crucial for managing this severe neurological disorder.
Area of Science:
- Neonatal screening
- Neurology
- Genetics
Background:
- Infantile Krabbe disease (IKD) is a severe, progressive neurological disorder.
- Early diagnosis and hematopoietic stem cell transplant (HSCT) by 30 days of age are critical for IKD management.
- The Recommended Uniform Screening Panel in the US now includes IKD screening.
Purpose of the Study:
- To evaluate if the two-tier newborn screening (NBS) strategy for IKD causes clinically relevant delays.
- To compare diagnosis timing between NBS using psychosine (PSY) analysis and PSY testing at follow-up.
Main Methods:
- Retrospective review of PSY analyses on dried blood spots from infants <28 days old over 6 years.
- Data sorted by ordering site and final diagnosis.
Main Results:
- Infants diagnosed via NBS with abnormal PSY results received their diagnosis 7 days sooner on average.
- HSCT occurred by day 36 of life on average for IKD cases detected by two-tiered NBS.
Conclusions:
- Effective NBS for Krabbe disease necessitates PSY as a second-tier test.
- This strategy enables timely treatment initiation and minimizes false positives.
- PSY inclusion in NBS algorithms and adjusted timeliness metrics are recommended for IKD.
Purpose:
Infantile Krabbe disease (IKD) is a severe, progressive neurological disorder that was recently added to the Recommended Uniform Screening Panel in the United States. IKD is a critical condition that requires a hematopoietic stem cell transplant, preferably by 30 days of age. This study examines whether the 2-tier newborn screening (NBS) strategy (psychosine [PSY] analysis when enzyme activity is low) causes clinically relevant delays compared with PSY measured at a first clinical follow-up visit.
Methods:
We reviewed the PSY analyses performed over a 6-year period on dried blood spots on infants < 28 days old. Results were sorted by the ordering site and final diagnosis.
Results:
On average, infants with a positive NBS for IKD that included abnormal PSY received their diagnosis 7 days sooner than whose PSY testing was initiated during follow-up. Hematopoietic stem cell transplant occurred by the 36th day of life, on average, for cases with IKD detected by 2-tiered NBS.
Conclusion:
Effective NBS for Krabbe disease requires the use of PSY as a second-tier test, allowing for timely initiation of treatment while virtually eliminating false-positive results. PSY should be included in NBS algorithms for Krabbe disease, and timeliness metrics need to be adjusted.
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