Fabry disease is an inherited disorder characterized by the accumulation of a special form of fat called globotriaosylceramide. This fat can accumulate in body cells from childhood, causing atypical symptoms throughout the body. (1)

It is a progressive and multisystemic lysosomal pathology, i.e. a pathology impacting structural elements involved in cell metabolism. The associated clinical attacks are renal, cardiovascular, cerebrovascular or even vestibular (associated with hearing). (2)

The characteristic signs of the disease are episodes of pain felt in the hands and feet (acroparesthesia), small red spots on the skin (angiokeratomas), decreased ability to sweat (hypohidrosis), visual disturbances (corneal opacity), gastrointestinal symptoms, ringing in the ears (tinnitus) or hearing loss.

Fabry disease usually results in lifelong treatment that can damage kidney function, cause heart attacks or ischemia. (1)

Some affected people have an intermediate form of the disease that develops a little later in the subject’s life. This pathological form affects only the heart and kidneys. (1)

The prevalence at birth for this disease is 1 / 80 (number of cases in a given population at a given time). In addition, it would appear that this figure is underestimated in the eyes of scientists.

When the disease develops later, this prevalence increases to 1 / 3. (000)

Fabry disease is determined by a broad spectrum of characteristic symptoms which can range from mild cases for heterozygous women (having two different alleles for the gene of interest) to more severe cases for homozygous boys (having two identical alleles for the gene of interest). gene of interest). However, patients with this pathology can all present with neurological, cutaneous (angiokeratomas), renal (proteinuria, renal abnormalities, etc.), cardiovascular (cardiomyopathies, arhythmias, etc.), cochleo-vestibular (hearing impairments) and / or cerebrovascular (ischemia, heart attacks, etc.). (2)

Symptoms of Fabry disease can range from mild to severe in severity. Pain is the most important clinical manifestation in this pathology. It is a chronic pain characterized by burning sensations, tingling, or by episodic attacks of intense burns. These pains may decrease around adulthood.

In addition, anhidrosis or hypohidrosis (absence or weakening of sweating) may appear causing intolerance to heat and exercise.

Other signs are also typical of the disease, such as: (2)

– an angiokeratoma: reddish skin lesions;

– changes in the cornea of ​​the eye;

– persistent fatigue;

– cardiac and cardiovascular abnormalities;

– dyspnea: respiratory discomfort resulting in shortness of breath;

– nephropathy: disease impacting the renal system.

Symptoms of the disease can be classified into two categories: mild manifestations and more severe symptoms. The first form more generally affects patients with this pathology and develops in childhood or adolescence. The second is less frequent and appears more generally in adulthood or at an advanced age (between 50 and 80 years). (2)

The clinical manifestations relating to the benign form are visual impairment (development of opacity in the cornea of ​​the eye), skin lesions, pain in the extremities and reduced ability to sweat (hypohidrosis ). Added to this, chronic abdominal pain and diarrhea can resemble this form of the disease. At an advanced age, the patient with this pathological type may see the development of other symptoms such as heart attacks. (3)

Regarding the more serious form of the disease, the associated symptoms are, this time, heart attacks (ventricular hypertrophy, cardiomegaly, ischemia, arrhythmia, etc.). In addition, kidney damage is often associated with it, resulting in dialysis or kidney transplantation in nearly 10% of cases. (3)

Fabry disease is an inherited genetic disease caused by mutations in the GLA gene. This gene of interest allows the production of an enzyme: alpha-galactosidase A. The latter has an important role within lysosomes, internal structures which, among other things, ensure cellular metabolism.

In a healthy organism, the correct functioning of the alpha-galactosidase A enzyme enables the organism to cope with the fatty substances characteristic of Fabry disease: globotriaosylceramides.

Mutations in the GLA gene therefore alter the structure and function of this enzyme. As a result, the body is no longer required to fight effectively against globotriaosylceramides. Either, these fatty substances therefore accumulate in the constituent cells of the organism, particularly at the level of the cells lining the wall of blood vessels, skin cells, kidney cells, heart cells or even the nervous system.

The gradual accumulation of these substances in the different cells leads to the development of certain clinical signs. (1)

The abnormal accumulation of this type of fat in the blood vessels leads to the formation of occlusions in them and reduces the vascular diameter. This leads to reduced blood flow and thus to a deficiency in the supply of different parts of the body (tissues and organs) with blood. All of the body’s blood vessels are usually affected, however small vessels in the skin, heart or nervous system may be more so. (3)

Certain mutations in the GLA gene can lead to the complete absence of alpha-galactosidase A production and thus lead to a severe form of Fabry disease. Other mutations can lead to a decrease in the biological activity of the enzyme. In the latter case, the development of the disease will be characterized by an intermediate form of Fabry disease, impacting only the heart and kidneys of the individual. (1)

This pathology is the consequence of a genetic anomaly within a gene carried by the X chromosome, the sex chromosome determining the sex of the individual. The transmission of the disease is of the “X-linked recessive” type. This sex chromosome is carried in a single copy by boys (XY) and in duplicate by girls (XX). In addition, the recessivity of this mode of transmission of the disease reflects the fact that the presence of two copies of the allele mutated for the gene of interest is necessary for the development of the associated phenotype. (3)

The risk factors associated with the disease are genetic. Indeed, the disease is transmitted by a recessive way linked to the X chromosome (sex chromosome).

In this sense, the individual must present the two mutated alleles for the gene of interest on his X chromosome to see the phenotype associated with the disease develop.

The differential diagnosis of Fabry disease is based on the development of characteristic symptoms in the patient. In addition, a blood test allows the analysis of the enzymatic activity of the enzyme alpha-galactosidase A. (3)

The diagnosis of Fabry disease is also based on: (1)

• a birth screening test;
• genetic analysis to highlight the presence of the mutated gene

Laboratory diagnostic tests involve enzymatic labeling. The enzymatic analysis then makes it possible to highlight the deficient functioning or even the absence of functioning of the enzyme alpha-galactosidase A. (2)

The usual treatments for Fabry disease are based on taking analgesics (reducing pain), drugs to act on kidney damage (angiotensin, etc.), antiarrhythmics, pace-makers, implantation cardiac defibrillators, dialysis or kidney transplantation. (2)

Patients with a severe form of the disease may benefit from drugs such as carbamazepines or diphenylhydantoins. These types of treatments are often taken every day to prevent and reduce pain as well as to reduce the risk of developing more severe symptoms (heart and / or kidney damage)

A specific treatment of the disease on an enzyme replacement is currently topical in research related to the disease. Indeed, the synthesis vitro alpha-galactosidase A enzyme allows replacement of the deficient or absent enzyme in the patient. This treatment has not yet been implemented for sick individuals but research is promising.

The risk of the disease affecting vital organs increases with an individual’s age. The final stage of the disease in terms of renal and cardiovascular damage limits the person’s life expectancy. (2)

It is also necessary to proceed with prevention in people with Fabry disease. Indeed, affected people are advised to avoid stressful situations, prolonged and repeated exposure to the sun or heat, to temperature changes or to avoid intense physical exercises. (3)