The lysosomal storage disorder Fabry disease (FD) is caused by pathogenic mutations in the α-galactosidase A gene, localized in X chromosome. Deficient enzymatic activity of the product of this gene, the lysosomal hydrolase α-galactosidase A, leads to accumulation of its substrate globotriaosylceramide. Diagnosis of FD starts with clinical suspicion followed by confirmatory laboratory testing. The aim of this work is to report the 14 years’ experience and learnings in the diagnosis of patients with Fabry disease in Argentina from a specialized lysosomal diseases diagnosis laboratory and to report the genotype characterization of the 25 families from Argentina with FD detected by us.
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.
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