[Fabry disease: clinical aspects and therapeutic perspectives].
Fabry's disease is one of the lysosomal disorders. It is due to a hereditary alpha-galactosidase A defect with X-linked recessive transmission. A majority of hemizygotes develop severe multisystemic involvement (classic form), dominated by relentless renal failure and progressive neurological and cardiac lesions. Nevertheless, some affected individuals retain sufficient enzyme activity and long remain asymptomatic (atypical form); their main manifestation is hypertrophic cardiomyopathy. Female carriers are usually asymptomatic; 15%, however, have severe involvement of one or more organs. Laboratory, histological and molecular diagnosis identifies 100% of hemizygotes and over 80% of heterozygotes. With recent developments in molecular genetics it is possible to produce the human recombinant enzyme alpha-GALA. Its effects in hemizygous patients remain to be evaluated. In addition, the results of a trial of gene therapy in a Fabry's disease gene knocked-out mouse appear promising. These new therapeutic approaches will probably soon provide substitutive treatment for Fabry's disease as well as for so-called "orphan" diseases.
Barbey
F
F
Service de néphrologie, INSERM U 507, Hôpital Necker, Paris.
Lidove
O
O
Droz
D
D
Grünfeld
J P
JP
D000818:Animals; D000795:Fabry Disease / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D005260:Female; D006580:Genetic Carrier Screening; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout