Fabry pedigree analysis: A successful program for targeted genetic approach.

Area of Science:

• Genetics
• Lysosomal storage disorders
• Rare diseases

Background:

• Fabry disease (FD) is an underdiagnosed X-linked disorder caused by alpha-galactosidase A deficiency.
• A significant diagnostic delay of over 10 years exists between symptom onset and diagnosis.
• Family screening is crucial for detecting undiagnosed individuals.

Purpose of the Study:

• To present a targeted genetic strategy for pedigree analysis in Argentina.
• To evaluate the effectiveness of family screening in diagnosing Fabry disease.

Main Methods:

• Implemented a strategy involving physician and family meetings upon index case diagnosis.
• Constructed family trees and performed genetic testing on relatives.
• Conducted pedigree analysis for 31 families.

Main Results:

• Tested 1,462 relatives, diagnosing 501 with Fabry disease.
• Achieved a positive detection rate of 33%.
• Obtained a high index-to-pedigree ratio of 1:15, the highest reported for FD.

Conclusions:

• The targeted family screening approach is effective in detecting undiagnosed Fabry disease patients.
• This strategy significantly improves the identification of individuals with FD.
• The study highlights the success of genetic pedigree analysis in managing Fabry disease.