Fabry disease: symptoms, diagnosis and treatment

Fabry disease is a rare, hereditary genetic defect caused by a partial or complete deficiency of a specific enzyme. By the time Fabry’s disease is diagnosed, most patients have had a true odyssey. What symptoms occur, how is the diagnosis carried out and what is the therapy like?

Fabry disease: what is it?

The alpha-galactosidase (alpha-GAL enzyme), which is missing in those affected by Fabry disease, is responsible for breaking down certain fatty substances in the body. If this process is disturbed, the substances cannot be digested and broken down by the body. Instead, they are deposited in cells throughout the body.

Such accumulations in blood vessels and tissues can lead to significant malfunctions in essential organ systems, for example: 

• in the heart
• in the brain
• in the kidneys

In the advanced stages, Fabry’s disease can even be life-threatening for those affected.

 

Fabry disease: incidence and heredity

Everyone always inherits an X chromosome from the mother and an X or Y chromosome from the father. If the father passes on an X chromosome, the child will be female (XX); if the child inherits a Y chromosome, it becomes male (XY).

In Fabry disease, the defective gene is located on the X chromosome. This is why men and women can carry an altered gene: everyone has at least one X chromosome. Because Fabry disease is an X-linked disease, there is no inheritance of the disease from father to son.

However, sick fathers pass the defective gene on to all their daughters. Women who have two X chromosomes and carry the genetic defect on one chromosome can be asymptomatic carriers or have different degrees of disease. In any case, they take a 50 per cent risk of passing the defective gene on to their offspring. Sons who inherit the diseased gene from their mother will always get the disease.

Important: Those affected should have their doctor draw up a medical family tree, which they can use better to assess the risk of inheritance of Fabry disease. Such a family tree can also be of use to living relatives and future generations – not only in the context of Fabry’s disease.

Diagnostics: How can you diagnose Fabry disease?

Diagnosing Fabry disease is not always easy. Because the symptoms are varied, they often appear in childhood or adolescence and change or intensify quickly. Because of its rarity, the disease often goes undetected, misunderstood, or even misdiagnosed.

Statistically, the diagnosis of Fabry disease is only made after about 25 years. By then, the patients had consulted an average of nine specialists, and their level of suffering was extremely high.

Family history often provides the first suspicion. A simple blood test that shows the activity of the alpha-GAL enzyme is sufficient to confirm this in men. In sick women – despite apparent disease symptoms – completely average enzyme values ​​can be found. Therefore, a more complex genetic analysis (1 to 2 months) is carried out on them for a precise diagnosis.

 

Fabry disease: symptoms and signs

These are typical symptoms of Fabry disease:

• The disease is characterized by intense, burning pain in the hands and feet that can radiate throughout the body. They usually appear in childhood and adolescence. The pain can be constant (chronic) or occur in attacks in so-called Fabry crises and then last for minutes or days.
• Most Fabry disease patients sweat little or not, which can trigger flare-ups because the body can no longer regulate its temperature.
• Reddish-purple skin rashes often appear between the navel and the knees in adolescence and are often used to identify the disease. They can be a few millimetres to the size of a pinhead.
• Many Fabry disease patients have gastrointestinal symptoms, especially after eating; sometimes, there is diarrhoea and nausea.
• More likely in adulthood and as a result of an illness that has existed for a long time, there are disturbances in the heart (e.g. cardiac arrhythmias, myocardial insufficiency, coronary artery occlusion), and the kidney function decreases (to the point of requiring dialysis).
• Dizzy spells and headaches manifest damage to the blood vessels in the brain, and in the worst case, there is a risk of an early stroke.
• Some people with Fabry disease experience radiating opacities in the cornea, which do not affect vision and can also be used for the initial diagnosis.

Important: Not all Morbus Fabry patients have all symptoms (simultaneously). Unfortunately, even the current absence of a symptom does not mean that it cannot appear. Women often have a milder course of Fabry disease.

Psychological consequences of Fabry disease

Those affected by Fabry disease tyre quickly under physical exertion and are often plagued by pain. In children and young people, this can lead to problems at school and with classmates – especially if the disease has not yet been diagnosed and treated. Because of the pain, many sufferers experience depression and hopelessness, and they feel isolated and alienated from others. It can, therefore, be helpful for them to join a self-help group where they can exchange ideas with others.

Fabry disease: therapy and treatment

Since the summer of 2001, it has been possible to administer the missing enzyme to Fabry disease patients as a regular infusion. By helping the drug, deposits in blood vessels and tissues can be prevented, and the enzyme can remove existing deposits. With this therapy, Morbus Fabry patients have a good chance of reaching an average age for the first time.

Important: The earlier the disease is detected, the easier it is to prevent further progression.