Fabry disease ... Angiokeratoma diffuse body; Deficiency alpha-galactosidase A (Fabry disease, Angiokeratoma corporis diffusum, alpha-galactosidase A deficiency) - Gen GLA.

Fabry disease is an inherited disorder that results from the accumulation of a particular type of fat called globotriaosylceramide, in the body cells. From childhood, this buildup causes signs and symptoms that affect many parts of the body.

The characteristic features of the disease include episodes of pain especially in the hands and feet, clusters of dark, small red spots on the skin, hipohidrosis, corneal opacity, problems with the gastrointestinal system, tinnitus and hearing loss. Fabry disease also involves life - threatening complications such as progressive kidney damage, heart attack and stroke. Some affected people have milder forms of the disease that appear later in life and affects only the heart or kidneys.

This process is due to mutations in the GLA gene, located on the long arm of chromosome (Xq22), encoding the enzyme alpha-galactosidase A. This enzyme is active in the lysosomes of cells, and is responsible for breaking down a molecule called globotriaosylceramide, which consists of three sugars attached to a fatty substance. This molecule is degraded as part of the normal recycling of erythrocytes and other cell types.

They have identified more than 370 mutations in the GLA gene that cause Fabry disease. Mutations in the gene GLA alter the structure and function of the enzyme, preventing effectively degrade globotriaosylceramide. As a result, globotriaosylceramide accumulates in cells throughout the body, particularly in the cells lining blood vessels in the skin and kidney cells, heart and nervous system. The progressive accumulation of globotriaosylceramide leads to the variety of signs and symptoms of the disease. Some genetic mutations result in an absence of alpha-galactosidase A, causing severe form of Fabry disease. Mutations that reduce but do not eliminate, the activity of the enzyme usually cause milder, late - onset disease affecting only the heart or kidneys forms.

This disease is inherited in an X - linked pattern A condition is considered X - linked if the mutated gene that causes the disorder is on the X chromosome in males, an altered copy of the gene in each cell is sufficient to cause disease. In women, an altered copy of the gene in each cell leads, generally, to milder symptoms or may cause no symptoms at all. Unlike other X - linked disorders, Fabry disease causes significant health problems in many women who have an altered copy of the GLA gene. These women may experience many of the classic features of the disease, including nervous system abnormalities, kidney problems, chronic pain and fatigue. They also have a higher risk of developing high blood pressure, heart disease, stroke and kidney failure. Signs and symptoms of Fabry disease usually start later in life and are milder in women than their male relatives affected. Some women who carry a mutation in one copy of the gene never develop any of the signs and symptoms of the disease.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with Fabry disease, by complete PCR amplification of the exons of the GLA gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).