Fabry disease (Fabry syndrome) is a rare, progressive, hereditary metabolic disease that is caused by a disorder in the breakdown of fat in the body’s cells as a result of an enzyme deficiency. Affected males show a more pronounced course than females. Enzyme replacement therapy can slow down the course of Fabry disease and limit secondary diseases.
What is Fabry disease?
Morbus Fabry or Fabry syndrome is a rare genetic metabolic disease that is associated with a disruption in enzyme activity. See lawfaqs for Definitions of Melorheostosis.
In Fabry disease, there is an organism-wide deficiency of the enzyme alpha-galactosidase as a result of reduced or absent synthesis of the enzyme. Alpha-galactosidase regulates the breakdown of certain lipid metabolites in the lysosomes (cell organelles responsible for breaking down foreign substances).
Due to the disruption of this fat breakdown, glycosphingolipids, primarily ceramide trihexoside, are deposited in the cells, which leads to the cell damage characteristic of Fabry disease and even to their death.
Fabry disease is a genetic deficiency of the enzyme alpha-galactosidase, which leads to a disruption in the breakdown of fat in the lysosomes of cells (lysosomal storage disease). In Fabry disease, there is a genetic defect on the X chromosome (X-chromosomally inherited disease), which results in impaired synthesis of the enzyme.
In Fabry disease, this manifests itself either in a complete absence or in a reduced concentration of alpha-galactosidase in the organism or in the synthesis of an inactive or only weakly active form of the enzyme.
The resulting accumulation of glycosphingolipids, in particular the non-degradable ceramide trihexoside, in the endothelial cells (inner wall cells of the lymphatic and blood vessels) and smooth muscle cells of the blood vessels as well as in the nerve cells of the central and peripheral nervous system causes the symptoms that are significant for Fabry disease.
Symptoms, Ailments & Signs
It is characteristic of Fabry disease that men are affected to a much greater extent and more frequently than women. In women, the disease usually begins later with an overall milder course of the disease. The first symptoms appear in the first decade of life. This leads to sudden pain attacks in the feet and hands.
The pain subsides within a few days. Furthermore, the patients suffer from tingling and burning in the hands and feet, which can be exacerbated by temperature fluctuations. In addition, nausea, vomiting and diarrhea are often observed in children. This can lead to malnutrition through chronic loss of appetite. Sweating is often reduced.
This can lead to heat shock during physical exertion. Some patients also sweat more. So-called angiokeratomas develop on the buttocks, groin, thighs or belly button. These are benign red-purple skin elevations caused by local dilation of blood vessels.
Corneal opacities can also occur very early. In later stages, the kidneys, heart and brain are increasingly affected. Without treatment, these organ involvements inevitably lead to death over the course of the disease. Renal failure usually begins in the second or third decade of life and used to be the most common cause of death from Fabry disease.
Furthermore, heart diseases such as angina pectoris, cardiac arrhythmia or heart valve defects often occur. Strokes, which are caused by vascular changes in the brain, often occur before the age of 50.
Diagnosis & History
In the case of Fabry disease, an initial suspicion is based on characteristic symptoms such as changes in the eyes (changes in the cornea, clouding of the lens), bluish-red to blackish changes in the skin and mucous membranes (so-called angiokeratomas), paresthesia (tingling and/or numb, burning sensation in the hands or feet), disturbances in heat regulation of the body (decreased or increased sweating) as well as hearing loss and proteinuria (protein in the urine).
The diagnosis of Fabry disease is confirmed by determining the alpha-galactosidase activity and ceramide trihexoside concentration in the blood. A missing or reduced activity of the enzyme as well as an increased concentration of ceramide trihexoside indicate Fabry disease. In addition, the diagnosis can be confirmed by means of a kidney biopsy and a genetic test.
Morbus Fabry usually has a progressive, lethal (deadly) course and, if left untreated, leads to damage to the kidneys (renal insufficiency), heart (heart valve insufficiency) and brain (ischemic strokes). However, the symptoms and complications of Fabry disease can be limited by starting treatment early.
Those affected suffer from severe pain due to Fabry disease. These can also occur in the form of rest pain and lead to sleep disturbances or other complaints, especially at night. Sensitivity disorders or paralysis of various parts of the body can also occur, making everyday life difficult for the patient.
Those affected also suffer from increased perspiration and various changes to the skin. These can also have a negative impact on the aesthetics of the patient. If Fabry disease is not treated, it can also lead to problems with the cardiovascular system, which in the worst case can lead to the death of the person affected. The patient’s quality of life is significantly reduced by Fabry disease.
Hearing impairment or, in the worst case, complete deafness can also develop. Those affected can also suffer and die from kidney failure. Infusions are used to treat Fabry disease. As a rule, those affected are dependent on lifelong therapy, since a causal treatment of the disease is not possible. In some cases, a kidney transplant is also necessary. Patients must also ensure a healthy lifestyle and generally abstain from nicotine.
When should you go to the doctor?
Pain, as well as pain attacks, should be presented to a doctor. If they occur, there is a need for action as soon as possible. You should refrain from taking pain medication until you have consulted your doctor, as there is a high risk of possible complications. In case of vomiting, diarrhea, nausea or a general feeling of being unwell, a doctor is needed. If you lose your appetite or lose weight unintentionally, you should see a doctor to find out the cause. Decreased sweat production is a sign of a health condition that should be investigated. If a feeling of inner dryness occurs during physical exertion, there is a risk of dehydration in severe cases. This puts the patient in a potentially life-threatening condition
A doctor is also required in the event of fluctuations in body temperature or sensory disturbances. A tingling sensation in the limbs or a burning sensation should be presented to a doctor. A blurred vision or clouding of the cornea are signs of a condition that needs to be evaluated and treated. In the case of general functional disorders, irregular heart rhythms and circulatory disorders, a doctor’s visit is advisable.
Reduced performance or persistent psychological problems should be discussed with a doctor so that the cause can be clarified. Since Fabry disease can lead to the death of the affected person if left untreated, a doctor’s visit should take place as soon as the first discrepancies arise.
Treatment & Therapy
Morbus Fabry is usually treated causally as part of an enzyme replacement therapy with genetically synthesized alpha-galactosidase. The infusion of synthetic alpha-galactosidase compensates for the enzyme deficiency and alleviates the symptoms by gradually breaking down the metabolites stored in the cells, while at the same time further accumulation is prevented.
Accordingly, the progression of the disease can be significantly slowed down by enzyme replacement therapy. Since the synthetic enzyme is also degraded within these endogenous degradation processes, regular (usually every two weeks) and lifelong infusions are required. While the first infusions should take place under medical supervision, these can also be carried out as part of home therapy in the further course of therapy and if the drug is well tolerated.
In addition, the existing symptoms and complaints are treated in parallel (symptomatic therapy). In an advanced stage of Fabry disease, which is often associated with kidney failure, dialysis or a kidney transplant may be necessary. A low-fat diet, sufficient fluid intake, abstinence from nicotine consumption and the avoidance of stress and pain-causing factors are also recommended for Fabry disease.
Outlook & Forecast
It is crucial for the prognosis of all Morbus Fabry sufferers that the disease is recognized and treated at an early stage. If left untreated, more and more damage to vital organs develops due to the increasing accumulation of globotriaosylsphingosine (LysoGb3) until they can no longer perform their function. For those affected who are not treated, the average life expectancy is 50 years for men and 70 years for women.
Compared to the total population, this corresponds to a reduction in life expectancy of 20 or 15 years. Those affected eventually die from end – stage renal failure or from cardiovascular or cerebrovascular complications such as cerebral hemorrhage, stroke, or myocardial infarction. With adequate and early treatment, the prognosis is good.
In general, the later the diagnosis and the start of treatment, the greater the reduction in life expectancy. If nephropathy (kidney disease) or advanced cardiomyopathy (heart muscle disease) has already developed, this has a negative impact on the prognosis. Repeated strokes and transient ischemic attacks (circulatory disorders in the brain) worsen the prognosis. In addition, renal, cerebrovascular and cardiovascular complications can reduce life expectancy.
In individual cases, strokes and transient ischemic attacks can even occur as the first manifestation of Fabry disease. According to one study, 50 percent of male and 38 percent of female victims suffered their first stroke before the initial diagnosis was made.
Since Morbus Fabry is a genetic metabolic disease, there are no preventive measures. However, an early diagnosis and an early start of therapy can positively influence the course of the disease and limit secondary diseases. For example, Fabry disease can be diagnosed in the children of an affected parent as part of prenatal diagnostics as early as the 15th week of pregnancy, which ensures an early start of therapy.
In the case of Fabry syndrome, the follow-up measures are very limited in most cases. Since it is a hereditary disease, it cannot usually be completely cured. Those affected are therefore dependent on an early diagnosis so that there are no further complications or worsening of the symptoms.
If you want to have children again, a genetic test and counseling can be carried out to prevent the syndrome from recurring. Those affected with Fabry syndrome are usually dependent on taking various medications. The doctor’s instructions should be followed, and the doctor should always be contacted first if there are any questions or if anything is unclear.
Since the disease cannot be completely treated, some of those affected are dependent on dialysis or, in the further course, on a kidney transplant. The support and care of one’s own family also has a very positive effect on the further course of the disease and can also prevent depression or other mental upsets. In many cases, Fabry syndrome reduces the life expectancy of those affected.
You can do that yourself
The diverse symptoms in the area of digestion and the gastrointestinal tract can be counteracted with a suitable and balanced diet. It helps many patients to keep a food diary and thus to be able to classify the tolerance of different foods for themselves. Here, those affected make a note of which foods they have eaten and when. At the same time, subsequent gastrointestinal symptoms are also written down so that possible intolerances can be analyzed.
There is no general nutritional recommendation, since every patient suffers from various digestive problems and the food selection should therefore be adjusted to individual needs. Basically, experts advise Fabry disease patients to eat as little fat as possible. In the advanced stage of the disease, special diets may become necessary, since the kidney function can be impaired, for example, by a diet rich in sodium (too much salt).
For many of those affected, contact with a self-help group is also helpful. The exchange with other patients is an important support, especially for the psychological suffering that can accompany the disease. Tips for dealing with Fabry disease on a day-to-day basis can also be shared. Contact points and discussion groups can be found online.