Le mutazioni alla base della malattia di Fabry: come orientarsi tra quelle che causano e quelle che non causano la malattia

Abstract

Mutations underlying Fabry’s disease: how to get oriented between those that cause and those that do not cause the disease

Anderson-Fabry disease is a rare, progressive, multisystem, accumulation’s disorder caused by partial or total deficiency of the lysosomal enzyme α-GAL A. Fabry disease is an X-linked lysosomal enzymopathy determined by mutations in the GLA gene, coding for α-GAL A. To date, almost 900 mutations in Fabry patients have been described.

Results:

In our laboratories we studied the genetic and enzymatic alterations on almost 17,000 patients with systemic symptoms referable to Fabry disease. In 461 of these patients, exonic mutations in GLA were so classified: 73.5% of the mutations have been associated with classical phenotype, 17.2% with atypical variants, and 9.4% with GVUS.

Conclusions:

The considerable number of patients we studied, allowed us to demonstrate that there is a complete relationship between symptoms, genetic and enzymatic findings and Lyso-GB3 accumulation. Our study shows that in all patients with causative mutation, who have absent or reduced enzymatic activity, we find hematic Lyso-GB3 accumulation, commensurate with the type of mutation and always according with the patient symptomatology.