Fabry disease (FD) is a progressively developing and hereditary lysosomal storage pathology that generates neurological, kidney, skin, cardiovascular and cerebrovascular problems. It usually affects men more; Women usually have a milder form or are asymptomatic carriers.
Causes of Fabry disease
Absence of enzyme activity
Fabry disease appears to be caused by the absence of activity of the lysosomal enzyme alpha-galactosidase A linked to mutations in the GLA gene. This lack of activity causes a fatty substance (glycolipid) that should be broken down by this enzyme to accumulate in the lysosomes of the cells. This causes the accumulation of globotriaosylceramide (Gb3) in lysosomes; organelles formed by the Gobi apparatus, an organelle that belongs to the endomembrane system and is found in all eukaryotic cells (cells formed by a nucleus and cytoplasm compartmentalized by membranes).
The severity of the disease depends on the type of mutation. There are children who show symptoms from the age of three.
Symptoms of Fabry disease
Wide range of symptoms
The characteristic symptoms of Fabry disease are very varied and affect various parts of the body. It can cause:
– Periodic attacks of severe pain in the extremities. They last minutes or days and can be caused by fatigue, stress or changes in environmental humidity and temperature. They decrease with age.
– Absence of sweat or decreased sweating.
– Vascular injuries in the hips, back, thighs, buttocks, penis and scrotum. They increase with age.
– Fabry waterfall.
– Heart problems (arrhythmias, heart muscle disease, heart attack…).
– Cerebrovascular diseases.
– Kidney failure.
– Arterial hypertension.
– Gastrointestinal problems.
– Varicose veins.
– Hemorrhoids.
– Deafness.
Diagnosis of Fabry disease
Analysis to verify the absence of enzyme activity
Diagnosing Fabry disease is not easy. It often goes unnoticed and patients are wrongly diagnosed with other types of disorders. Many times there is a delay in diagnosis of more than ten years from the onset of symptoms until it is finally concluded that it is Fabry disease. Blood tests can demonstrate the absence of activity of the enzyme alpha-galactosidase.
It is easy for many patients to be diagnosed with hypertrophic cardiomyopathy or ventricular hypertrophy. This delays the diagnosis of Fabry which means the treatment is less effective.
Fabry disease treatment and medication
Research in progress
Conventional treatment consists of pain relief with analgesic medications, kidney protection, antiarrhythmic agents, pacemakers or implantable defibrillators, dialysis, and kidney transplantation. Another specific therapeutic option for the disease is currently being investigated, which is enzyme replacement therapy using alpha-galactosidase A synthesized in vitro. If the gene mutation allows deficient production of the enzyme, treatment with a pharmacological chaperone can be considered, a molecule that attaches to the residual protein and changes its structural conformation to improve its activity.
Over the years, continued damage develops in vital organ systems, which can lead to organ failure. End-stage kidney disease and life-threatening cardiovascular or cerebrovascular complications limit life expectancy in untreated men and women with a reduction of 20 and 10 years of life, respectively, compared to the general population.
Prevention of Fabry disease
Genetic study
Being able to do genetic studies of the entire family can help detect affected individuals in early stages.
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