The Gaucher disease (EG) is a pathology of genetic origin that is characterized by its clinical heterogeneity, from the asymptomatic forms to the Severe neurological conditions (Giraldo et al., 2008).
At the biomolecular level, Gaucher disease is caused by a deficient activity of the lysosomal beta-glucocerebrosidase enzyme which, as a result, Leads to an abnormal storage of glycosylceramide (fatty substance) in different structures, including liver, spleen, Bones, lungs, or the nervous system (Capablo Liesa et al., 2011).
On the other hand, at the clinical level, signs and symptoms can begin to develop from infancy or adulthood, some of them include Lesions, malformations and visceral pathologies and / or nerve lesions (National Institute of Neurological Disorders and Stroke, 2016).
Thus, the diagnostic suspicion of this pathology is based on the clinical findings, presence of visceromegalias, bone pain, anemia , Etc., whereas the diagnosis is confirmed through a study of enzymatic activity (Gilando, 2011).
Currently, there are several therapeutic approaches designed for Gaucher disease, many of them, aimed at enzymatic substitution.
Although it has important benefits for those affected, in some cases, secondary neurological complications Related to this pathology (Giraldo et al., 2008).
Characteristics of Gaucher disease
Gaucher disease is a metabolic disorder, rare in the general population and hereditary in nature, whose signs and symptoms Characteristics are due to poor enzymatic activity (National Organization for Rare Disorders, 2014).
This pathology was initially described by Dr. Philipe Gaucher in 1882. In his clinical report he described the case of a woman affected by a An abnormal increase in the size of one of its upper extremities, associated with an abnormal accumulation of fatty material (Spanish Association of the Sick And Family of Gaucher Disease, 2016; National Gaucher Foundation, 2016).
He Metabolic system Human is responsible for regulating all processes related to the generation and recycling of those substances that are vital For our survival.
This is pre-programmed for us to produce, among others, substances called enzymes, that is to say, molecules of protein character that, Catalyze or accelerate biochemical reactions and processes.
Specifically, one of the products we produce is called the glucocerebrosidase, whose essential function is the decomposition and recycling of a type of lipid, Fatty substance, called glucoesfingolígicos, like glucosilceremida (National Human Genome Research Institute, 2012).
Specifically, in Gaucher disease, the presence of certain genetic alterations, leads to a deficient production of the enzyme Glucocerebrosidase. Thus, the Macrophages , Cells responsible for collecting these fatty substances begin to store them inside (Association Spanish Society of Family Sick People of Gaucher's Disease, 2016).
Consequently, the absence of metabolization leads to an abnormal accumulation of fatty substances in the organism, especially in organs, Bone structure or the nervous system (National Institute of Neurological Disorders and Storke, 2016).
Types
As we have pointed out, in the clinical course of Gaucher disease, enzymatic deficiencies involve fat accumulation in different regions and Systems of organism.
Although Gaucher's disease has a heterogeneous symptomatological pattern and, really variable in its severity, this pathology has been Object of different classifications that try to categorize their characteristics (National Gaucher Foundation, 2016).
Thus, depending on the level of neurological and multisystemic involvement, Gaucher disease has been classified classically into three types (Capablo Liesa Et al., 2011; National Institutes of Health, 2014):
- Type I Gaucher Disease : It is considered the most prevalent type and is characterized by the absence of neurological involvement with Presence of visceral and bony anomalies.
- Gaucher Disease Type II : In this case, the clinical presentation is early, mainly in childhood. In addition, the The neurological alterations are serious, reason why can lead to the death of the person affected.
- Type III Gaucher Disease : Although the severity is lower than in the previous cases and the clinical presentation allows The survival of the affected person, signs and symptoms may appear associated with the neurological, visceral and bone area.
About us
It is estimated that Gaucher disease has a prevalence of approximately 1 case per 50,000-100,000 people in the general population (Genetics Home Reference, 2016).
Depending on the classification described above, it has been observed that Type I is the most common at the clinical level and, in addition, it is associated with a A significant increase in the number of cases in the Central and Eastern European areas (Genetics Home Reference, 2016).
Interestingly, the prevalence of Gaucher disease amounts to 1 case per 500-1,000 people of aschkenazí descent, The inhabitants of Jewish origin settled in Central and Eastern Europe (Genetics Home Reference, 2016).
However, the other forms of Gaucher disease described are not usually highly prevalent, they are uncommon in the general population and Are not associated with geographical regions or particular ethnic or cultural groups.
Signs and symptoms
As we have pointed out, Gaucher disease presents a variable clinical course, with a significant affectation of different body systems.
While some people lack significant symptoms or medical complications, others experience chronic pathologies and often, Potentially deadly (Mayo Clinic, 2015).
However, there is a set of signs and symptoms that occur most frequently in most affected persons (National Organization For Rare Disorders, 2014; Mayo Clinic, 2015; Spanish Association of Patients and Families of Gaucher's Disease, 2016):
Neurological affectation
Neurological alterations are the most serious medical condition, often the symptoms usually appear from the earliest stages of development Of Gaucher's disease, typically during childhood. In addition, with features in forms II and III.
- Muscle hypotonia / spasticity: Accumulation of Lipids Nerve areas responsible for motor regulation may Development of various alterations related to tension or muscle tone. In the case of hypotonia, an abnormal reduction of Tone or muscle flaccidity, while in the case of Spasticity , A high stiffness or muscular tension can be observed, usually characterized by Involuntary contractions.
- Ataxia: The muscular pathologies described above, seriously impair the coordination and execution of movements or Motor acts.
- Convulsive episodes: Neurological involvement may lead to the development of spontaneous neuronal discharges with a course disorganized. Thus, the most frequent is to observe a brief episode in which the person shakes his body involuntarily and uncontrollable. The Muscular structure tends to contract and, in many cases, fainting or loss of consciousness occurs.
- Visual paralysis: In some cases, it is possible that neurological involvement occurs at the level of the nervous tracts it controls Ocular function and coordination. It is possible that some affected individuals may have difficulty or inability to perform voluntary movements Horizontal or vertical with your eyes.
- Generalized delay of development: In general, there is a considerable delay in acquiring the Development, walking, walking, language, etc. In addition, in cases of late filing, it is possible to observe a significant deterioration of some Cognitive functions, attention problems, memory problems, difficulty concentrating, inability to solve problems, etc.
Bone Impairment
As in the previous case, the accumulation of fatty material in the bone structure, will cause a series of medical pathologies, among which we can find:
- Bone crisis : These crises are characterized by the presence of episodes of intense pain, especially in the long bones. Further, These are usually accompanied by inflammation and even abnormal or pathological elevation of body temperature. Bone crises are especially common In the presentation of Gaucher's disease.
- Osteopenia : It is a medical condition characterized by a decrease in bone volume, ie bone mineral material.
- Osteoporosis : Pathological decrease of bone volume leading to an exaggerated increase in the fragility of the bone structure bodily.
- Osteonecrosis or Avascular Necrosis : It is a pathology produced by a decrease or interruption of the blood supply of some Particular bone area. When the bone tissue does not receive blood supply, its cells can die and, therefore, could collapse by decomposing or sinking Under its structure.
Visceral affectation
Visceral signs and symptoms usually affect the liver, lungs, or extremities. Some of the most common pathologies Include:
- Hepatomegaly : This medical condition is characterized by an abnormal or pathological increase in liver volume. The liver is Involved in the regulation of various functions of our organism, therefore, this pathology can lead to the development of another type of Disorders related to this structure, such as liver failure.
- Splenomegaly: In this case, there is a pathological increase in arm size. The involvement of this structure can cause Persistent pain, nausea, vomiting, among others.
- Interstitial lung disease: This type of pathologies usually occur with the development of inflammation or scar tissue Pulmonary diseases. Among other functional consequences, it is possible that the affected person presents respiratory insufficiency or Aspiration pneumonias .
- Dropsy: This term, is often used in the medical literature to refer to a generalized or focused accumulation of Liquid or fatty material in body tissues.
Hematologic Affectation
Lipid storage can also affect normal or expected hematological functioning, so it is possible that various changes occur Related to imbalances in its components:
- Thrombocytopenia : In this case, there is a significant decrease in the levels of Blood platelets , Therefore, occurs An imbalance of blood clotting, and abnormal or recurrent bleeding may occur.
- Anemia: In this case there is a decrease in the volume or size of red blood cells. They are in charge Mainly of the transport of oxygen towards the corporal organs and tissues. As a consequence, among the symptoms that may appear is the Headaches , Recurrent fatigue and fatigue, dizziness, shortness of breath, etc.
Causes
Gaucher disease has a genetic origin, the three forms (Type I, Type II and Type II), are due to autosomal recessive traits, that is, one Individual will present his clinical statement if he inherits the same defective gene from each parent (National Organization for Rare Disorders, 2014).
Specifically, the cusa of this pathology is associated to the presence of a mutation in the gene that controls the production of the enzyme Glucocerebrosidase, located on chromosome 1, at location 1q21 (National Organization for Rare Disorders, 2014).
Diagnosis
In the presence of several signs and symptoms of those described above, there may be clinical suspicion of Gaucher disease.
After the study of individual and family history, physical and neurological examination, the diagnosis is fundamentally based on the Performance of a biochemical laboratory study of the enzyme beta-glucocerebrosidase. Normally, its concentration in dry blood of Leukocytes and Fibroblasts (Gort and Coll, 2011).
In addition, a genetic study is often performed to detect the possible presence of anomalies compatible with Gaucher disease, and thus Confirm their diagnosis (Gort and Coll, 2011).
Treatments
Gaucher disease is a type of disorder in which both the underlying medical symptoms and their cause can be treated at the medical level Etiological
Thus, generally the therapeutic interventions are of the pharmacological type and are oriented to the enzymatic replacement, that is to say, the enzyme is replaced Deficient through artificial management (Mayo Clinic, 2015).
In addition, there are also other types of drugs, such as Miglustat Or the eliglustat, that interfere in the production and accumulation of fats in the Tissues of the body (Mayo Clinic, 2015).
In most cases, these interventions are effective for the treatment of Gaucher's disease, however, in severe cases or stages Advanced, structural injuries, such as neurological ones, are difficult to repair.
References
- AEEFEG. (2016). Gaucher disease . Retrieved from the Spanish Association of the Sick and Familiars of Gaucher Disease.
- Alfonso Palacín, P., & Pocoví, M. (2011). Genetics of Gaucher disease. Genotype-phenotype correlation. Med Clin (Barc) , 17-22.
- Capablo Liesa, J., Sáez de Cabezón, A., Alarcia Alejos, R., & Ara Callizo, J. (2011). Clinical features of neurological forms of Gaucher disease. Med Clin (Barc) , 6-11.
- Giraldo, P. (2011). Guideline for action in patients with Gaucher disease. Med Clin (Barc) , 55-60.
- Giraldo, P., Capablo, J., Alfonso, P., Latre, P., García, B., & Pocovi, M. (2008). Neurological manifestations in patients with Gaucher disease And their families. Med Clin (Barc) , 175-179.
- Gort, L., & Coll, M. (2011). Diagnosis, biomarker and biochemical alterations of Gaucher disease. Med Clin (Barc) , 12-16.
- Mayo Clinic. (2015). Gaucher's disease . Obtained from Mayo Clinic.
- NGF. (2016). What is Gaucher Disease? Retrieved from the National Gaucher Foundation.
- NIH. (2012). Learning About Gaucher Disease . Retrieved from the National Human Genome Research Institute.
- NIH. (2014). Gaucher Disease . Obtained from MedlinePlus.
- NIH. (2016). Gaucher Disease . Retrieved from the Genetics Home Reference.
- NIH. (2016). Gaucher Disease Information Page . Retrieved from the National Institute of Neurological Disorders and Stroke.
- NORD. (2014). Gaucher Disease . Retrieved from the National Organization for Rare Disorders.
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