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Fabry disease, also known as GLA deficiency, is a rare genetic disease characterized by an absence or reduction in the activity of the enzyme α-galactosidase A, or α-Gal A. Symptoms may include episodes of severe pain in the hands and feet, decreased or absent sweat production, dark spots on the skin (angiokeratomas), cloudiness or streaks toward the front of the eye and problems with the heart and kidneys. Fabry disease belongs to a group known as lysosomal storage disorders, and can arise in childhood (known as “classic” Fabry disease) or in adulthood (known as “atypical” or “late-onset” Fabry disease). In both cases, Fabry disease can result in kidney failure and/or heart disease, which can be fatal. Fabry disease is inherited in an X-linked pattern, which means male patients, who only have one X chromosome, are at higher risk of severe symptoms, while some female patients may be asymptomatic.
- Severe pain, especially triggered by exercise, fatigue, stress and/or fever
- Decreased or absent sweat production
- Small dark red spots on the skin (angiokeratomas) caused by widening of tiny blood vessels called capillaries near the surface of the skin
- Heart problems including abnormal heart rhythm or enlargement of the heart’s main pumping chamber (the left ventricle)
- Kidney disease
- Cloudiness or streaks toward the front of the eye
- Gastrointestinal problems
- Fatigue and weakness
- Hearing loss
- Increased risk for stroke
Fabry disease is caused by pathogenic variants, also known as mutations, in the GLA gene. As a result of the enzyme deficiency caused by pathogenic variants, toxic substances build up in cells and tissues throughout the body, leading to the symptoms of Fabry disease.
How Fabry disease is diagnosed
Physicians may suspect a diagnosis of Fabry disease based on medical history, physical exam and/or family history. Classic Fabry disease may be suspected based on characteristic symptoms including episodic pain, skin lesions, absent sweat production and/or gastrointestinal issues, among others. Fabry disease may be detected in newborn screening panels, but is implemented in only some U.S. states. Type 1 Fabry is typically identified in childhood or adolescence, while later onset Fabry is not usually detected until age 40 or later. In male patients with type 2 Fabry, diagnosis is often missed until cardiac and/or kidney problems arise in adulthood. Diagnosis of Fabry disease is confirmed by testing α-Gal A enzyme activity and/or genetic testing.
Current treatments are geared toward slowing the multi-organ dysfunction characteristic to Fabry disease. Enzyme replacement therapy (ERT) is available for Fabry diseases and entails intravenously infusing a synthetic enzyme. Research on ERTs for Fabry suggests that they can help improve or slow progression of some symptoms, including pain and progression of kidney disease. In the U.S. and in many other countries internationally, there is also a commercially available treatment known as oral chaperone therapy for patients with specific pathogenic variants in the GLA gene. Chaperone therapy increases α-Gal A enzyme activity and studies suggest it may help with some symptoms of Fabry. Other treatments target specific symptoms of Fabry disease, including dialysis or transplant to treat kidney disease and medications to treat pain.
In various studies in Europe and Asia, pathogenic variants associated with classic Fabry disease were found in 1 in 22,000–40,000 males. Pathogenic variants associated with atypical (later onset) Fabry disease are present in approximately 1 in 1,000–3,000 males and 1 in 6,000–40,000 females.
Fabry disease belongs to a larger group of metabolic conditions called lysosomal storage diseases (LSDs). LSDs are genetic conditions involving the lysosomes, which act much like recycling centers within cells. When lysosomes are unable to work correctly, substances build up in cells that cause symptoms of LSDs. There are more than 50 different known LSDs.
- Fabry Support & Information Group
- National Fabry Disease Foundation (NFDF)
- Canadian Fabry Association
- MPS Society
- Children's Neurology Foundation
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We are currently recruiting patients to help make this Fabry research database as strong as possible. We hope to fuel multiple future research projects and studies, and will keep participants updated on our progress.