Newborn screening for neuropathic lysosomal storage disorders

Area of Science:

• Biochemistry and Genetics
• Neonatal Medicine
• Rare Diseases

Background:

• Growing interest in newborn screening (NBS) for lysosomal storage disorders (LSDs) driven by new therapies and diagnostic technologies.
• Enzyme replacement therapy (ERT) is ineffective for central nervous system manifestations, limiting NBS for most neuronopathic LSDs.
• Krabbe disease is an exception where early intervention via hematopoietic stem cell transplantation improves outcomes.

Purpose of the Study:

• To review the current status of LSD screening programs.
• To discuss the challenges in detecting neuronopathic LSDs through NBS.
• To highlight the importance of phenotype prediction for patient management.

Main Methods:

• Review of existing literature and current practices in newborn screening for LSDs.
• Analysis of enzyme activity measurement as a primary screening tool.
• Discussion of the role of genotyping in predicting disease severity and phenotype.

Main Results:

• NBS for LSDs typically detects both severe neuronopathic and milder forms due to reliance on enzyme activity.
• Expansion of NBS to include conditions like Gaucher disease, Niemann-Pick A/B, and mucopolysaccharidoses is anticipated.
• Distinguishing between neuronopathic and non-neuronopathic subtypes based on screening data is a significant challenge.

Conclusions:

• Accurate prediction of phenotypes using enzyme activity and genetic information is essential for appropriate patient care in NBS for LSDs.
• Further research is needed to refine screening methods for better differentiation of LSD subtypes.
• Effective management strategies must account for the limitations of current NBS approaches for neuronopathic LSDs.