Consensus recommendations for the classification and long-term follow up of infants who screen positive for Krabbe...

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Krabbe Disease (KD) is a rare, severe lysosomal storage disorder.
• Newborn screening (NBS) identifies infants at risk for KD, but classification and follow-up protocols require refinement, especially for late-onset forms.
• Current diagnostic pathways can lead to extensive, sometimes unnecessary, follow-up testing.

Purpose of the Study:

• To establish updated, consensus-based recommendations for classifying infants who screen positive for Krabbe Disease.
• To provide clear guidelines for the long-term follow-up of individuals at risk for late onset Krabbe Disease (LOKD).
• To optimize the efficiency of diagnostic and follow-up processes for KD NBS positive infants.

Main Methods:

• A panel of Krabbe Disease experts (KD NBS Council) convened from July 2017 to June 2020 to develop consensus recommendations.
• Recommendations were based on galactocerebrosidase (GALC) enzyme activity, psychosine concentration, and GALC genotype.
• The proposed classification and follow-up pathways were validated using a historical cohort of 47 newborns from New York State.

Main Results:

• A three-tiered clinical follow-up pathway was established: Early Infantile KD, at-risk for LOKD, or unaffected.
• Infants at risk for LOKD were further stratified into high-risk and low-risk groups based on GALC genotype.
• Application of the updated recommendations to the historical cohort demonstrated an 88% reduction in necessary follow-up testing.

Conclusions:

• The KD NBS Council has developed updated, consensus-driven recommendations for classifying and managing infants identified through newborn screening for Krabbe Disease.
• These guidelines enhance the efficiency of classification and focus on effective long-term follow-up strategies for individuals at risk of LOKD.
• The revised approach aims to reduce unnecessary testing while ensuring appropriate monitoring for at-risk infants.