Fabry disease: the many faces of a single disorder.

Abstract

In 1898, two dermatologists, William Anderson in England and Johannes Fabry in Germany, separately described a disease characterized by skin lesions, known as angiokeratomas. This issue contains two reports of Fabry disease (FD) patients presenting with proteinuric chronic kidney disease (CKD) but lacking angiokeratomas [1, 2]. These cases illustrate the phenotypic heterogeneity of the disease in females [1] and FD variants [2], the role of genetic diagnosis [1] and renal biopsy [2] and recent advances in pathophysiology [1]. FD is caused by deficient activity of alpha-galactosidase A (α-GalA) due to mutations in the X-chromosome GLA gene, leading to accumulation of neutral glycolipids and eventual tissue injury and organ dysfunction [3]. In classical FD males, α-GalA activity is absent or nearly absent and there is an early onset of acroparesthesias, angiokeratoma and hypohydrosis followed by life-threatening cardiac, central nervous system and kidney disease leading to end-stage renal disease (ESRD) at a mean age of 40 years [3, 4].