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Fabry disease

Also known as: Anderson-Fabry disease, Angiokeratoma Corporis Diffusum, Haemorrhagic Nodular Glycolipid Lipidosis

Background

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.

Credits

Last updated March 2016 by Dr D Hughes, Senior Lecturer in Haematology, Royal Free London NHS Foundation Trust and University College London, UK.

Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information is provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

What are the symptoms?

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
  • tinnitus.

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.

How is it diagnosed?

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.

How is it treated?

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.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Fabry disease is inherited in an X-linked manner. Affected families should be referred to a genetics centre for information and support.

Prenatal diagnosis
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.

Is there support?

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