Evidence and Recommendation for Infantile Krabbe Disease Newborn Screening

Area of Science:

• Genetics and rare diseases
• Lysosomal storage disorders
• Newborn screening

Background:

• Krabbe disease (KD) is a rare, fatal autosomal recessive lysosomal disorder caused by GALC gene variants, leading to psychosine accumulation and neurodegeneration.
• Infantile KD (IKD) presents by 12 months with severe symptoms and early childhood death if untreated.
• Hematopoietic stem cell transplantation (HSCT) can improve IKD survival but is most effective when performed early, before symptom onset.

Purpose of the Study:

• To highlight the importance of newborn screening for Krabbe disease (KD).
• To discuss the role of GALC activity and psychosine levels in KD diagnosis.
• To emphasize the need for support systems for families undergoing early KD diagnosis and treatment decisions.

Main Methods:

• Newborn screening for KD utilizes low galactosylceramidase (GALC) levels in dried-blood spots.
• Second-tier testing for elevated psychosine concentration enhances screening specificity for infantile KD (IKD).
• Recent inclusion of IKD in the Recommended Uniform Screening Panel by the US Secretary of Health and Human Services.

Main Results:

• Newborn screening enables earlier diagnosis of IKD, potentially before clinical symptoms manifest.
• Early diagnosis facilitates timely intervention with hematopoietic stem cell transplantation (HSCT).
• The effectiveness of screening for later-onset KD phenotypes remains uncertain.

Conclusions:

• Implementing robust systems for IKD newborn screening is crucial for maximizing treatment benefits.
• Support for families in making rapid decisions regarding HSCT is essential.
• Ensuring prompt access to HSCT post-diagnosis is vital for improving outcomes in infantile Krabbe disease.