Agalsidase alfa--a preparation for enzyme replacement therapy in Anderson-Fabry disease.

Anderson-Fabry disease is an X-linked multisystemic disorder caused by a genetic deficiency of the lysosomal enzyme a-galactosidase A. The enzyme is responsible for degradation of glycolipids inside the lysosomes. Lack of catalytic activity leads to progressive depositions of undegraded glycolipids in a large number of organs. Crises of severe pain in the extremities (acroparesthesias), hypohidrosis, corneal opacities and dysfunction of several organs (kidney, brain, heart) are the leading symptoms in patients with Anderson-Fabry disease. Females may have the same symptoms as males but to a more variable degree. The variable manifestations seen in heterozygotes can be explained by the Lyon hypothesis. This hypothesis predicts that in X-linked diseases, the carriers are a mosaic of normal and mutant cells in varying proportions and hence have variable expression. As in Gaucher's disease, enzyme replacement therapy recently became available for Anderson-Fabry disease. Two drugs have gained approval in the EU by the European Agency for the Evaluation of Medicinal Products. These are agalsidase beta (Fabrazyme, Genzyme Corporation) and agalsidase alfa (Replagal, Transkaryotic Therapies, Inc.). This review will describe clinical efficacy, safety and tolerability of agalsidase alfa.