Angiokeratoma corporis diffusum – Fabry disease: historical review from the original description to the introduction of enzyme replacement therapy

Abstract

This paper gives a brief historical overview of Fabry disease. First described in 1898 and called angiokeratoma corporis diffusum, a succession of observations and pioneering clinical research over the past 100 years has led to our present understanding of the disease. The major milestones during this time are described, as is the work that resulted in the successful introduction of enzyme replacement therapy.

The Fabry disease-associated lipid Lyso-Gb3 enhances voltage-gated calcium currents in sensory neurons and causes pain

“…Fabry disease (OMIM 301500) is a lysosomal storage disorder caused by a deficiency or absence of the enzyme α-galactosidase A, due to mutations of the X-linked gene GLA [1] . As a result, unmetabolised glycosphingolipids accumulate in various types of cells including neurons of the dorsal root ganglia (DRG) [2] .…”

A modified lipid composition in Fabry disease leads to an intracellular block of the detergent‐resistant membrane‐associated dipeptidyl peptidase IV

“…Fabry disease (Anderson-Fabry disease) is an X-linked lysosomal storage disorder caused by deficiency of αgalactosidase A (AGAL, gene symbol GLA, NM_0001692) (Fabry 2002) and results in abnormal accumulation of glycosphingolipids that are associated with several clinical signs and symptoms. So far, more than 400 mutations have been described in the coding sequence of AGAL (Stenson et al 2003), many of which are specific for one family (Scriver et al 2001).…”

Endocrine Dysfunction in Patients with Fabry Disease

“…F ABRY DISEASE (FD) was first described in 1898 by two dermatologists who published two cases of diffuse angiokeratoma (1). During the last century, involvement of the heart, kidney, brain, and gastrointestinal system has enriched the clinical picture of FD, which has been recognized as a multiorgan disease caused by ␣-galactosidase-A (␣-gal) deficiency and consequent systemic accumulation of globotriaosylceramide (Gb3) (2)(3)(4)(5)(6)(7)(8)(9).…”