What is Fabry Disease?

    Fabry Disease is a condition which takes it name from a German scientist, who first encountered it in 1898. It is also known as ‘Fabry-Anderson Disease’ or ‘a-galactosidase A deficiency syndrome’. The condition is extremely rare, with approximately 15 families identified in Ireland at present as having at least one family member affected with Fabry disease.

    Enzymes are used by the body to break down large molecules, making them available for catabolism by the body. Specific enzymes are matched to break down specific substances. Fabry disease is the result of a genetic mutation which prevents the body from naturally producing a specific type of enzyme: a-galactosidase.

    The a-galactosidase enzyme, normally present in the lysosome part of a cell, is responsible for the breakdown of a type of lipid, known as globotriaosylceramide (abbreviated to GL3 or Gb3). The lack of this enzyme causes an accumulation of the GL3 lipid in cells, tissues, vessels and fluids around the body.

    The accumulation of GL3 lipid leads to a range of symptoms characterised initially by pain in the hands and feet, and distinctive skin lesions on the lower back. Untreated, the continued deposition of GL3 can cause progressive organ damage, particularly in the kidneys, heart and central nervous system, and can ultimately reduce life expectancy to about 40 years in affected males.

    Renal dialysis has helped to address kidney problems, but much more significant has been the introduction of enzyme replacement therapy (ERT). Initial responses to ERT are very positive. Early diagnosis of Fabry, and access to ERT, is therefore essential.

    The genetic defect is X-linked recessive. This means that symptoms are displayed more prominently in males than in females. More recent research and identification of an increasing number of patients has revealed that the condition can affect women much more than initial estimates, and that a large number of variants exist who suffer different degrees of the symptoms.

    The estimation that appears to be accepted by clinicians is that between 1 in 40,000 – 100,000 males are affected with Fabry. This figure is believed to apply to males with ‘classic Fabry’. The disorder is panethnic, and it is estimated that there are between 5,000 – 10,000 patients worldwide.