Also known as: Anderson-Fabry disease; Angiokeratoma Corporis Diffusum; Haemorrhagic Nodular Glycolipid Lipidosis
Fabry disease is a rare genetic metabolic condition. It is caused by changes (mutations) in the GLA gene, which provides instructions for making an enzyme called alpha-galactosidase A. Because of this there is a build-up of a fatty substance called globotriaosylceramide (GL-3 or GB-3), in cells throughout the body, particularly cells lining blood vessels in the skin and cells in the kidneys, heart, and nervous system. Males with the condition are usually more severely affected than females.
Last updated March 2019 by Professor D Hughes, Professor of Experimental Haematology , Royal Free London NHS Foundation Trust and University College London, UK.
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Symptoms of the classic form, in males with low activity of the enzyme, usually become apparent in childhood or adolescence. They include:
- acroparesthesias (severe pain in the hands and feet)
- angiokeratomas – small dark red/purple raised spots composed of surface dilated capillaries (small blood vessels)
- hypohidrosis (reduced sweating)
- cloudiness of the front part of the eye (corneal opacity)
- bowel disturbance
Gradual deterioration of kidney function usually occurs in men. They may also develop heart problems such as an enlarged heart and neurological problems, including stroke. Males with a higher level of enzyme activity are more mildly affected. They show features later in life, mostly with heart or kidney problems with few of the other symptoms.
Females typically have milder symptoms at a later age of onset than males. However, this is very variable. Some females may be relatively asymptomatic (have no symptoms) throughout a normal life span or may have symptoms as severe as those observed in males.
In males demonstration of low alpha-gal A activity in blood, or skin cells that are grown in the laboratory (cultured) can make a diagnosis. In females, measurement of alpha-galactosidase A activity is unreliable. Molecular genetic testing of the gene encoding the alpha-galactosidase A enzyme is the most reliable method for identification of females with Fabry disease.
The introduction of enzyme replacement therapy has offered the opportunity to treat the underlying cause of Fabry disease. Intravenous infusion of recombinant alpha-galactosidase An enzyme has been shown to clear deposits of GB-3, stabilise kidney function, reduce heart size and significantly improve pain and quality of life. Enzyme is administered intravenously every two weeks. In the UK most patients receive enzyme replacement at home. Oral treatment is also approved and will be suitable for some patients.
Other treatments can be given to relieve the symptoms of Fabry disease. For example, nerve pain can be treated using antiepileptic drugs such as gabapentin and carbamezapine. Angiokeratomas may be removed or treated with laser therapy. Standard therapies such as aspirin, antihypertensives, ace-inhibitors for protein in the urine and anti-cholesterol agents are used to treat the renal (kidney), cardiovascular and vascular symptoms of the disease.
Fabry disease is inherited in an X-linked manner. Affected families should be referred to a genetics centre for information and support.
Prenatal testing is available for affected families by either chorionic villus sampling (CVS) or amniocentesis. Preimplantation genetic diagnosis may be available for families in which the disease causing mutation has been identified.
Information and support in the UK for Fabry disease is available from the MPS Society (see entry Mucopolysaccharide diseases and Associated diseases).