Newborn Screening in Fabry Disease

Area of Science:

• Genetics
• Lysosomal Storage Disorders
• Newborn Screening

Background:

• Fabry disease (FD) is an X-linked genetic disorder caused by alpha-galactosidase A deficiency, leading to globotriaosylceramide accumulation and organ damage.
• Symptoms are heterogeneous and nonspecific, causing diagnostic delays. Newborn screening (NBS) offers early detection but faces challenges.
• Prevalence is higher than previously thought, particularly with variants of unknown significance (VUSs).

Purpose of the Study:

• To review recent studies on NBS for Fabry disease.
• To analyze screening methods, prevalence data, and natural history.
• To assess the benefits, risks, and controversies of FD NBS.

Main Methods:

• Systematic review of pilot studies and screening programs for Fabry disease.
• Analysis of diagnostic methods, prevalence estimates, and VUS interpretation.
• Evaluation of ethical, clinical, and economic aspects of NBS programs.

Main Results:

• FD prevalence exceeds 1 in 40,000 males, higher than earlier estimates, partly due to VUSs.
• Pilot studies highlight controversies in interpretation, cost-effectiveness, and clinical management.
• NBS provides an opportunity for early diagnosis and treatment initiation.

Conclusions:

• NBS for FD is feasible and identifies more cases than previously known.
• Further research and standardized protocols are needed to address interpretation, cost, and psychosocial impacts.
• Optimizing screening program design is crucial for improved health outcomes and manageable burdens.