Fabry pedigree analysis: A successful program for targeted genetic approach

Abstract

Background Fabry disease (FD) is an X‐linked disorder of glycosphingolipid catabolism caused by a deficiency of the lysosomal enzyme alpha‐galactosidase A ( GLA ). FD is still an underdiagnosed disorder worldwide. Moreover, there is delay between symptom onset and Fabry diagnosis of at least 10 years. Family screening offers an important benefit for detection of new patients. The aim of this work is to present the approach along with the results of a targeted genetic strategy for pedigree analysis for FD in Argentina. Methods By this strategy as soon as a new index Fabry patient is diagnosed, the pedigree group contacts the physician and a meeting is arranged with the physician and the family to build the family tree. Results Pedigree analysis was carried out for full in 31 families. In the work period, we have tested 1,462 relatives, and 501 were diagnosed FD. The proportion of positive detection was 33%. Conclusion The targeted family screening approach is successful to detect undiagnosed Fabry patients. By this approach, the highest ratio index to pedigree ever reported for FD pedigree analysis of 1:15 was obtained.

Clinical utility of urinary mulberry bodies/cells testing in the diagnosis of Fabry disease

“…Genetic testing of at-risk family members may improve the early diagnosis of FD; however, potential barriers have been identified, including screening and treatment costs, local regulations, and cultural issues [ 19 ]. Similar to our targeted genetic approach, several studies have reported the benefits of clinical genetic approaches using genetic counseling and family screening [ 20 , 21 ]. These programs included predictive genetic testing, which could have adverse psychological effects on clients [ 22 , 23 ].…”

The Benefits of Family Screening in Rare Diseases: Genetic Testing Reveals 165 New Cases of Fabry Disease among At-Risk Family Members of 83 Index Patients

“…Therefore, genetic testing of all at-risk family members (including males and females) should be encouraged [ 44 ]. Ideally, every patient newly diagnosed with Fabry disease should be referred to a medical geneticist for interpretation of the identified genetic variants and a detailed pedigree review [ 34 , 45 ]. However, the pedigree can also be drawn by any healthcare professional who is willing to spend time interviewing index patients and family members, in accordance with international guidelines [ 34 ].…”

Chronic renal failure in Fabry disease: the long-term survival on renal replacement therapy

“…Основной причиной были плохие внутрисемейные связи и отсутствие общения, что часто было связано с географическим фактором. По данным семейного скрининга, проведенного в других странах, количество родственников с БФ, выявляемых на каждого пробанда, было выше и достигало 10 человек [26,27]. При этом у большинства родственников отмечались малосимптомное течение БФ и отсутствие тяжелых органных поражений.…”