Pedigree analysis of Mexican families with Fabry disease as a powerful tool for identification of heterozygous females

Abstract

Fabry disease (FD) is an X-linked lysosomal storage disease caused by α-galactosidase A deficiency; in contrast to other X-linked diseases, heterozygous females can be as affected as men. The construction and analysis of a family pedigree is a powerful tool to aid clinicians in diagnosis, establishment of inheritance pattern, and early detection of potentially affected relatives. The present study highlights the importance of pedigree analysis in families with FD for identifying other possibly affected relatives and investigating the clinical manifestations. This clinical report included 12 Mexican index cases with confirmed FD diagnosis. We constructed and analyzed their pedigree, and diagnosed FD in 24 affected relatives. Clinical features were similar to those reported for other populations. Pedigree analysis further identified an additional 30 women as possible carriers. We conclude that pedigree construction and analysis is a useful tool to help physicians detect and diagnose relatives at risk for FD, particularly heterozygous females, so that they can receive genetic counseling and early treatment. Mexican families with FD were similar to other populations reported in the literature, and our findings confirmed that heterozygous females can have signs and symptoms ranging from subtle manifestations to the classical severe presentation described in males.