The Fabry's disease Is an inherited pathology that is related to an accumulation of a particular type of lipid in different Structures of the organism (Genetics Home Reference, 2016).
This medical condition has a genetic origin associated to the X chromosome and its clinical characteristics are caused by the presence of levels Deficient of the α-galactosidase enzyme (Martínez-Menchón et al., 2004).
The clinical course of Fabry disease (PE) may occur early in life, especially in males and may include signs and symptoms Symptoms such as neuropathic pain, hypohidrosis, skin lesions, corneal abnormalities, fatigue fatigue, hearing loss, Heart failure, renal failure and / or stroke (Guelbert et al., 2015).
The severe multisystemic involvement of PE will lead to a significant deterioration in the quality of life , Which can lead to Development of other secondary medical pathologies and even the early death of those affected (Barba Romero et al., 2012).
The diagnosis of PE is usually made based on the existence of a defined clinical picture, in addition, an analysis of Laboratory of the enzymatic activity and a genetic study to confirm the pathology.
The treatment used in PE is intended to prevent the development of secondary medical complications and to compensate for the deficit Enzymatic activity (Ortiz and Brown, 2003). In this case, therapeutic intervention through enzyme substitution has proven to be widely effective in The prolongation of hope and quality of life (Barba Romero et al., 2012).
Characteristics of Fabry disease
Fabry disease (PE) is a genetic pathology, the symptoms of which occur as a result of the accumulation of Lipids In the cells of Different organs and structures of our body (Genetics Alliance, 2016).
In the organism there are thousands of active substances, among which are the enzymes. The Enzymes , Constitute a type of protein molecule that Have a prominent role in the regulation and / or acceleration of certain biochemical reactions.
Thus, for example, in the intestinal structure, we have enzymes that help us to break down food to regulate the digestive process and extraction Of the essential nutrients for the organism (Genetics Alliance, 2016).
In addition, a good part of these enzymes are stored in a specific region of the cellular structure, denominated Lysosome . It is able to provide To the support body for the breakdown of lipids, carbohydrates and proteins (Genetics Alliance, 2016).
Thus, in Fabry disease, the functioning or lack of an enzyme essential for the metabolism of lipids and other substances Similar, called Α-galactosidase , Causes insufficient degradation.
Therefore, lipids tend to accumulate in different regions of the Organism such as the nervous system, cardiovascular system, apathetic, ocular, etc. (National Institute of Neurological Disorders and Stroke, 2016).
With the passage of time, the development of pathology and the persistent accumulation of substances thanks, will begin to appear different manifestations Clinics that will include neurological, renal, cardiac, cutaneous, vestibular alterations, among others (Orphanet, 2012).
In addition, Fabry disease presents two clinical forms, classified according to their intensity and / or severity:
- Type 1 or"classic": affects Mainly to men and is characterized by the complete presentation of the clinical course of this patrology.
- Type 2 or"Late onset": may Systematically affect both sexes and is characterized by the partial or incomplete presentation of the clinical course, generally with a higher intensity (National Institute of Neurological Disorders and Stroke, 2016).
About us
Fabry disease is a rare medical condition in the general population. Statistical studies show that it has a prevalence of Approximately 1 case per 40,000-60,000 people (Genetics Home Reference, 2016).
On the other hand, in relation to the incidence of Fabry syndrome, it has been pointed out that there may be one case per 80,000 live births per year. Without However, this information can vary substantially if one considers those cases in which the definitive diagnosis is established late (Orphanet, 2012).
As for its distribution by sex, is a disorder that affects mainly males, however, there is a milder form, which can occur With more in women (Genetics Home Reference, 2016).
Characteristic signs and symptoms
Although the symptoms are differentially expressed between the phenotypic forms of Fabry's disease and among patients, some authors García de Lorenzo et al., (2011), point out some of the most frequent clinical features in this pathology organized according to their evolution temporary:
Clinical characteristics during childhood and adolescence
- Persistent pain and acrosopesthesia : The development of distal pain in the upper extremities is one of the earliest symptoms of Fabry disease. However, with the evolution of the pathology, it is common that it becomes episodes of intense pain or burning in the hands and feet. The period of presentation usually varies, but it is common for the episode to last hours or days and, moreover, are usually triggered by the presence of Fever, stress, or physical exercise.
- Eye abnormalities : Ocular alterations are mainly related to the accumulation of lipids in the Corneas . Despite That in initial stages does not usually affect the capacity of vision, however, can cause structural and functional alterations in the vessels Blood vessels.
- Changes related to sweating : In many of the affected people there can be a decrease or absence Significant of sweating, resulting in a serious problem for the regulation of body temperature.
- Gastrointestinal disorders : In this case, the Diarrhea , Recurrent vomiting, or cramps and discomfort ABS.
- Tiredness and fatigue : Generalized intolerance to physical exercise and / or activities with a high motor intensity usually appears.
Clinical characteristics during adulthood (18-40 years)
- Development of angiokeratomas : It is a type of alteration related to the development of lesions in the skin, it is frequent the appearance Blisters, red spots or lifts and lumps.
- Hematuria : Renal anomalies can lead to small deposits of blood in the urine.
- Renal Chronic Disorders : They are characterized by the development of nephropathies, renal insufficiency and / or reduction of the capacity of Urinary concentration.
- Changes related to sweating : As in the earliest phase of Fabry's disease, a Significant decrease or absence of sweating.
- Increased body temperature : Poor sweating can hinder the ability to decrease and control the High body temperatures, therefore, it is common at this stage for affected persons to have recurrent episodes of fever.
- Arrhythmias : The affectation of the cardiovascular system can lead to the development of an alteration or irregularity of the frequency or heart rate.
- Abdominal pain and diarrhea: Intestinal anomalies continue to be related to persistent stools and discomfort Abdominals, in addition, it is also possible to develop cases of intestinal malocclusion.
- Tiredness and fatigue: As in the first phase, the physical capacity is usually severely impaired, so it usually appears A generalized intolerance to physical exercise and / or activities with high motor intensity.
Clinical characteristics during late adulthood (40 years or older)
- Cardiac abnormalities and abnormalities : The clinical course of Fabry disease may reach most tissues Cardiac disorders. We can observe the development of an increase of the heart volume, ventricular hypertrophy or alterations of the cardiac rhythm.
- Chronic ranchial alterations : The cellular and vascular lesions in this system progress to chronic renal failure, The use of therapeutic measures such as dialysis Or transplantation.
- Development of accidents and cerebro-vascular alterations : The deposits of fatty substances in the blood vessels located in Nervous regions, especially in brain , Can occlude or reduce blood circulation and, therefore, lead to the development of episodes Ischemic or hemorrhagic.
In addition, if we consider the two types of clinical presentation of Fabry's disease, we can point out that the most common signs and symptoms in each One of them are the following (National Organization for Rare Disorders, 2015):
- Type I : Acroparesthesia, hypohidrosis, gastrointestinal disorders, corneal dystrophy, angiokeratomas, fatigue and fatigue, nausea, Renal alterations, cardiac alterations, headache , among other.
- Type II : Cutaneous lesions, pain crisis, movement intolerance or Corneal dystrophy . In general, at this stage, the symptoms Presented with a reduced intensity.
On the other hand, several symptoms related to the psychological domain in Fabry's disease (Genetics Alliance, 2016) have also been described:
- Feelings of depression or hopelessness.
- Isolation.
- Denial of pathology and / or symptoms.
Causes
Fabry disease presents an inherited nature, associated to the presence of genetic alterations linked to the X chromosome . Specifically, the Clinical pattern is related to a mutation of a gene located on this chromosome (Genetics Home Reference, 2016).
The etiological mutation of this pathology was identified in 1989, it was found to be related to the gene encoding the α-galactosidase enzyme in The position Xq 22.11 (Barba Romero et al., 2012).
The enzyme α-galactosidase or α-Gal A, has the essential function of breaking or decomposing glucose molecules of complex lipids, called Glycolipids : Globotriasoliceramida (GL-3), smooth-globotriasoliceramida (smooth-GL3).
Thus, when the genetic mutation affects the production of α-galactosidase, deficient levels of this enzyme will lead to less decomposition Of the glycolipids. Thus, there will be persistent accumulation of GL3 and other lipid substances at different cell locations (National Organization for Rare Disorders, 2015).
As a result, there will be progressive degeneration of cells from different structures, especially the heart, kidneys or system (National Organization for Rare Disorders, 2015).
Diagnosis
The clinical features of Fabry disease may appear in all affected individuals of either sex or age; however, it is more common That begin to develop later in the female sex (Genetics Alliance, 2016).
Thus, the diagnosis of this pathology begins with clinical suspicion: findings of renal or cardiac insufficiency, ictus Without known cause, hypertrophy Corneal, among others (Barba Romero et al., 2012).
In this phase, it is fundamental to collect data about family and individual medical conditions and history, with the objective of identifying the Possible presence of hereditary Fabry disease factors.
Once clinical findings, consistent with a possible enzyme deficiency, are observed, a Α-galactosidase or α-Gal A in the body.
Generally, the most commonly used laboratory test is blood testing. Once a small blood sample has been extracted, it is possible to observe the Concentrations of α-galactosidase (Genetics Alliance, 2016).
If a poor concentration is detected, then a genetic confirmation study of Fabry's disease, specifically, It is necessary to detect a mutation in position Xq 22.11.
In addition to this, it is important to rule out the presence of other medical conditions such as rheumatic pathologies, peripheral vascular syndromes or Neurological disorders .
Are there treatments?
There is no curative therapy for Fabry disease, however, enzyme replacement is a therapeutic intervention that has reported Important medical benefits (Cleveland Clinic, 2016).
Specifically, enzyme replacement therapy attempts to increase blood α-galactosidase concentrations and, therefore, reduce the Storage or lipid retention (Cleveland Clinic, 2016).
When it is possible to control lipid persistence, it is expected that the medical complications associated with multistémic lesions will Significantly. However, some symptoms such as pain or renal failure can be treated by pharmacological approaches.
Some of the drugs prescribed by medical specialists are the Phenytoin , Carbamazepine or Metoclopramide (Cleveland Clinic, 2016).
References
- Alliance, G. (2016). Fabry's Disease . Retrieved from National Center for Biotechnology Information, U.S. National Library of Medicine.
- Barba Romero, M., Rivera Gallego, A., & Pintos Morell, G. (2012). Comparison of patients from a Spanish registry of Fabry's disease in two periods of time. Med. Clin (Barc) , 379-384.
- Cleveland Clinic. (2016). Fabry Disease . Obtained from Cleveland Clinic.
- García de Lorenzo, A. (2011). Consensus for the study and treatment of Fabry disease. . Med Clin (Barc) , 178-183.
- Gilbert, N., Politei, J., Szlago, M., Robledo, H., Lescano, S., Giner de Ayala, A., & Angaroni, C. (2015). Evaluation of neuroimaging and Description of the multisystem compromise in a family with Fabry disease. Neurol. Arg. , 100-104.
- Martínez-Menchón, T., Nagore, E., Pérez-Ferriols, A., Febrer, I., Maiques Santos, L., & Fortea-Baixauli, M. (2004). Diagnosis and treatment Enzymatic substitution in Fabry's disease. Actas Dermosifiliogr , 436-439.
- NIH. (2016). Fabry disease . Retrieved from the Genetics Home Reference.
- NIH. (2016). Fabry Disease Information Page . Retrieved from the National Institute of Neurological Disorders and Stroke.
- NORD. (2015). Fabry Disease . Retrieved from the National Organization for Rare Disorders.
- Orphanet. (2012). Fabry Disease . Obtained from Orphanet.