Fabry Disease

What is Fabry Disease?

Fabry disease (sometimes also called Anderson-Fabry disease) is an uncommon inherited metabolic disease where there is a deficiency or dysfunction of an enzyme (alpha-galactosidase A) which usually breaks down fatty substances in the cells of the body. Without this enzyme functioning, these waste products build up within cells and cause progressive damage.

Fabry disease can be very difficult to distinguish from more common conditions and sufferers can go for years without a correct diagnosis being made.

What are the signs and symptoms of Fabry Disease?

A wide variety of signs and symptoms are associated with Fabry disease. A person with Fabry disease may not experience them all and the severity of symptoms can vary from person to person. This is why Fabry disease can be such a difficult condition to identify and diagnose, although a detailed family history can help.

A painful burning sensation in the hands and feet is often an early symptom, as are gastrointestinal problems such as cramps, frequent bowel movements, diarrhoea and nausea. Other body sites that can be affected include the skin, eyes, ears, kidneys, heart, brain and nervous system.

What are the causes of Fabry Disease?

Fabry disease results from abnormal deposits of a fatty substance, known as globotriaosylceramide (Gb3, sometimes abbreviated as GL-3, and also known as ceramide trihexoside [CTH]). Normally, Gb3 is metabolised (broken down) by an enzyme called alpha-galactosidase A (a-Gal A). In people with Fabry disease, the gene that would normally tell the body to produce this enzyme is altered (often called a gene mutation). This alteration means that the enzyme does not work properly or is completely absent. This in turn leads to a build-up of Gb3 in cells of blood vessels, kidneys, brain, eyes and other organs. It is because of this build-up that Fabry disease is referred to as a storage disorder, and because the build-up happens in a part of the cell called the lysosome it is called a lysosomal storage disorder (also known as lysosomal storage disease).

Who is likely to be at risk of Fabry Disease?

Fabry disease is a rare inherited condition with the genetic alteration (called a mutation) being found in the X chromosome.

The chromosome pair that determines our gender contains either two X chromosomes for a female or an X and a Y chromosome for a male. Daughters (XX) inherit an X chromosome from their mother and an X chromosome from their father. Therefore, all daughters of an affected man will inherit one altered X chromosome from their father and one normal X chromosome from their mother meaning that symptoms of Fabry disease may not appear, or if they do, it will usually be later than in males. The symptoms of Fabry disease may also be less severe, which means females may be more difficult to identify. All of the sons of an affected man will inherit the Y chromosome from their father and the X chromosome from their mother and so will not be affected.

When the mother has Fabry disease, there is a 50% chance that each child born will also have Fabry disease. If boys inherit the altered X chromosome from their mother, they will develop symptoms, but if they inherit the normal X chromosome from their mother, they will not. If girls inherit the altered X chromosome then they may or may not show symptoms of Fabry disease.

It has been estimated that the incidence rate of Fabry disease in the general population is approximately one in 117,000 births.

How is Fabry Disease diagnosed?

Fabry disease can be diagnosed in males by demonstrating deficiency of α-galactosidase A activity. Enzyme activity is usually demonstrated in plasma, leukocytes or serum, or from tissue biopsies or cultured fibroblasts. Females who are heterozygous for Fabry disease cannot reliably be diagnosed by enzymatic assay. The level of α-galactosidase A activity in affected females can range from the low level found in affected males to well within the normal range.

What are the treatments for Fabry Disease?

Treatment of Fabry disease consists of two components; symptom management and replacement of the deficient or dysfunctional enzyme with enzyme replacement therapy (ERT). Treatment needs to be tailored to the individual. Because it is quite a rare condition, most people with Fabry disease are treated at specialist centres by doctors and nurses who are experts in treating lysosomal storage disorders like Fabry Disease. At these centres the patient and their family can be assessed by a range of medical specialists and advised on a specific treatment programme.

For further information go to: www.focusonfabry.com.