Dipl.-Biol. Birgit Busse, Dr. rer. biol. hum. Katrin Goldmann
Fabry disease is a lysosomal storage disease and X chromosomal inherited disorder of the glycosphingolipid catabolism. It is caused by a decrease in or absence of lysosomal enzyme alpha-galactosidase A (GLA) activity due to mutations in the GLA gene. The enzyme defect results in progressive systemic accumulation of glycosphingolipids in various tissues and organs. Early diagnosis and initiation of treatment is important to avoid severe complications. Symptoms of Fabry disease include angiokeratoma, episodes of pain and organ malfunction, which may lead to stroke, heart attack and kidney damage requiring dialysis as the disease progresses. Time of onset and course of the disease vary considerably, although problems frequently start in childhood.
The incidence of classic Fabry disease in men is estimated to be approx. 1 in 40,000. In contrast to other X chromosomal inherited diseases, heterozygous women are rarely asymptomatic and may develop symptoms covering the entire disease spectrum that require treatment.
Enzyme replacement therapy has been available in Europe since 2001; and since 2016, an oral chaperone therapy with the active substance migalastat has been available for patients over 16 with confirmed Fabry disease. Since the therapy is only effective in the presence of certain GLA gene mutations, the patient’s GLA genotype must be known. Individual mutations are listed in the summary of product characteristics for Galafold (migalastat).
Mehta and Hughes, 2002 Aug 5 [Updated 2017 Jan 5]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. / Schäfer et al. 2005, Hum Mutat. 25:412 / Eng et al. 1993, Am J Hum Gen 53:1186 / Fachinformation Galafold