Fabry disease (also known as alpha galactosidase) is a lysosomal storage disease and a congenital, X-linked disorder of the glycosphingolipid catabolism caused by a reduced or absent activity of the lysosomal enzyme alpha-galactosidase A (GLA). Pathogenic variants in the GLA gene are causative. The enzyme deficiency leads to a progressive systemic accumulation of glycosphingolipids in various tissues and organs. To avoid serious complications, an early diagnosis is crucial to initiate therapy. Symptoms of Fabry disease include angiokeratomas, pain attacks, and organ dysfunction, which may lead to stroke and myocardial infarction; dialysis may be required. Time of initial manifestation and course of the disease are highly variable, with symptoms commonly occurring in childhood.
The prevalence of classic Fabry disease in men is estimated at approximately 1:40,000. Unlike the majority of other X-linked disorders, heterozygous females are rarely asymptomatic and may develop symptoms requiring treatment or even present with the complete disease. One hypothesis for phenotypic variability in heterozygous women is skewed X inactivation.
Enzyme substitution therapy has been available in Europe since 2001. Since 2016, patients over the age of 16 with confirmed Fabry disease have the alternative option of oral chaperone therapy with the active ingredient migalastat. Since the therapy is only effective in the presence of certain variants in the GLA gene, the patient's GLA genotype must be known. A list of the individual variants can be found in the summary of product characteristics for Galafold.
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