Rare presentation and wide intrafamilial variability of Fabry disease: case report and review of the literature

Fabry disease (FD) is an X-linked genetic disease caused by mutations in the GLA gene, which encodes α-galactosidase A, leading to an intralysosomal accumulation of globotriaosilceramide (Gb3) in a wide variety of cells. Thus, FD usually presents with multiorgan damage: cardiac (hypertrophic cardiomyopathy), renal (chronic kidney disease, proteinuria), neurological (stroke, acroparesthesia), cutaneous (angiokeratoma), and ophthalmic (cornea verticillate) (1). Although FD is X-linked, women with specific mutations are not only carriers, as it was previously expected, but most of them develop manifestations somewhat later in life than men (2, 3), due to a mosaic inactivation of the X chromosome. It is of the utmost importance to follow the FD diagnosis with a complete family screening, which can lead to timely diagnosis in other family members. The present case report demonstrates how following the red flags of clinical suspicion for FD can lead to a correct final diagnosis in the index patient, even in case of a rare phenotypic presentation, while also highlighting the large intrafamilial variability of systemic FD manifestations.