Fabry's disease: clinical aspects and therapeutic perspectives

Fabry's disease is one of the lysosomal disorders. It is due to a hereditar y alpha-galactosidase A defect with X-linked recessive transmission. A majo rity of hemizygotes develop severe multisystemic involvement (classic form) , dominated by relentless renal failure and progressive neurological and ca rdiac lesions. Nevertheless, some affected individuals retain sufficient en zyme activity and long remain asymptomatic (atypical form); their main mani festation is hypertrophic cardiomyopathy. Female carriers are usually asymp tomatic; 15%, however, have severe involvement of one or more organs. Labor atory, histological and molecular diagnosis identifies 100% of hemizygotes and over 80% of heterozygotes. With recent developments in molecular geneti cs it is possible to produce the human recombinant enzyme alpha-GALA. Its e ffects in hemizygous patients remain to be evaluated. In addition, the resu lts of a trial of gene therapy in a Fabry's disease gene knocked-out mouse appear promising. These new therapeutic approaches will probably soon provi de substitutive treatment for Fabry's disease as well as for so-called "orp han" diseases.