Newborn Screening for Fabry Disease: Current Status of Knowledge

Area of Science:

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

Background:

• Fabry disease is an X-linked lysosomal disorder caused by alpha-galactosidase A deficiency.
• Delayed diagnosis leads to irreversible organ damage and reduced treatment efficacy.
• Newborn screening aims for early detection and intervention.

Purpose of the Study:

• To review the evolution and current status of newborn screening for Fabry disease.
• To discuss the advancements in diagnostic methodologies.
• To highlight persistent challenges and future directions in screening.

Main Methods:

• Application of standard enzymology fluorometric methods on dried blood spots.
• Development of high-throughput assays like digital microfluidics and tandem mass spectrometry.
• Implementation of DNA-based methods in select newborn screening programs.

Main Results:

• Newborn screening has been implemented globally using various techniques.
• Enzyme-based methods may miss affected females.
• Ethical considerations arise from identifying later-onset forms and variants of uncertain significance.

Conclusions:

• Long-term follow-up is essential to understand disease natural history and refine screening protocols.
• Improved knowledge will aid in evaluating the risks and benefits of newborn screening for Fabry disease.
• Universal acceptance of newborn screening for Fabry disease is still under consideration.