Fabry disease - current data and therapeutic approaches.

Abstract

Fabry disease represents an X-linked inherited disorder resulting in the accumulation of globotriaosylceramide (Gb3). This review explains the clinical manifestations and the possible therapies for this condition. Fabry disease is considered the second most frequent lysosomal storage disease. More than 1000 mutations of the galactosidase alpha (GLA) gene associated with this disorder have been identified. Pain, either episodic crises or chronic pain, is one of the earliest symptoms in Fabry disease. Gastrointestinal, ocular, ear or skeletal manifestations may complete the clinical picture. Cardiac and renal involvements are the most severe complications leading to organ failure and death. The cerebrovascular lesions may result in severe symptoms including stroke at younger ages. The diagnosis of Fabry disease may be put by enzymatic assays of the α-galactosidase A (AGAL-A) activity in plasma or leukocytes but genetic analysis remains the “gold standard” in identifying the precise mutation and even guiding the treatment. Enzyme replacement therapy (ERT) was the first step in treating subjects with Fabry disease. It proved important decrease of the number of sever clinical events and reduction of symptoms. Chemical chaperone therapy has many advantages including oral administration and was already approved in Europe and US, but it is suitable only for subjects with amenable mutations. Gene therapies (either ex vivo or in vivo) promise to represent a new era for many disorders including Fabry disease, the preliminary data being encouraging. Although many steps were taken in understanding the pathogeny of Fabry disease, future research is needed especially in the field of therapeutic approaches.