Genetic basis of Fabry disease
All cases of Fabry disease are caused by mutations in the gene GLA encoding the lysosomal hydrolase α-Gal A. The GLA gene is located on the X-chromosome, and the disease is inherited as an X-linked disorder. To date, more than 950 GLA gene mutations have been described. Type 1 Classically affected males have mutations that result in essentially no enzymatic activity, whereas patients with the Type 2 Later-Onset phenotype have mutations that retain low levels of residual enzyme activity. There are no common GLA mutations, and most GLA gene mutations are private, occurring in only one or a few families. For both phenotypes, the sons of affected males will not have the disease, whereas all daughters will be heterozygotes. For heterozygous females, there is a 50% risk of passing the GLA gene mutation onto their children with each pregnancy:
- • 50% of sons will be affected and 50% will not inherit the disease
- • 50% of daughters will be heterozygotes and 50% will not inherit the disease gene
