Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Fabry Disease

Dipl.-Biol. Birgit Busse, Dr. rer. biol. hum. Katrin Goldmann

Scientific Background

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.

Representation of the affected organs and the associated symptoms in Fabry disease Organ involvement and symptoms in Fabry disease
corneal clouding (cornea verticillata), cataracts (Fabry-cataracts) Eyes angiokeratoma, hypohidrose and subsequent increased temperaturesensitivity Skin proteinuria, weak kidneys, untreated it commonly leads to renal failure Kidneys cardiac arrhythmia, left ventricular hypertrophy Heart CNS circulatory disorders, headache, stroke, cognitive impairment Gastrointestinal tract abdominal pain, diarrhea, wind, nausea, vomiting Ears progressive hearing loss, deafness, tinnitus, dizziness nerve pain, burning pain in arms and legs (acroparesthesia) Nerves reduced bone density, osteopenia, osteoporosis Skeleton chronic cough, shortness of breath or respiratory distress duringphysical exertion Lungs Organ involvement and symptoms in Fabry disease (mod. vector graphic Freepik)

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).

Literature

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