Among the orphan (rare) diagnosis Gaucher disease is a special place. It refers to the accumulation of disease pathology, which is associated with the inability of the body to get rid of waste products.
- DISEASES ACCUMULATION ASSOCIATED WITH THE ACTIVITY OF LYSOSOMES
- WHAT ARE GAUCHER CELLS AND HOW THEY ARE FORMED
- GENETIC COMPONENT OF GAUCHER DISEASE
- AS THE DISEASE MANIFESTS ITSELF
- TREATMENT OF GAUCHER DISEASE
Diseases accumulation associated with the activity of lysosomes
Each cell is a separate organism in which there are processes of synthesis and degradation. Naturally, all the waste products of the cells must be disposed of in time, otherwise the cell loses the ability to normal functioning.
The cell has special organelles lysosomes, the main role of which consists in the splitting of unnecessary products. The lysosome contains a cocktail of different fissile enzymes and acids, which is sent for recycling cellular debris. Essentially the lysosome is the recycling plant of the cell, which works consistently and without side waste for the body.
As you understand, lysosomes perform important functions in the body, allowing you to maintain homeostasis, and if there are no enzymes in the organelle is not enough, then violations occur. Such diseases are called lysosomal storage diseases,. Found that patients diagnosed with such disease, the activity of key lysosomal enzymes is about 20% of normal. Thus, there is the unnecessary accumulation of waste products in the cell, which ultimately leads to her death and therefore the destruction of tissues and organs that are composed of these cells.
Lysosomes with accumulated glucocerebroside
What are Gaucher cells and how they are formed
In the composition of cell membranes have a specific complex fats glucocerebroside that consist of fats and carbohydrates. Normal, to maintain balance, these fats should degrade and formed again in new cells. In particular, glucocerebroside contained in the formed elements of the blood erythrocytes and leukocytes, and to maintain their vital functions required for optimal activity of the enzyme glucocerebrosidase, which breaks down complex fat. During aging of these cells, they are utilized by macrophages containing large amounts of lysosomes, which includes this enzyme.
Lysosomes of macrophages absorb glucocerebroside, however, if in the lysosomes is not enough enzyme, the fats begin to Deposit. And formed Gaucher cells. In the cells becomes more and more lysosomes filled with glucocerebroside, which have toxic effects on cells.
In Gaucher disease primarily affects the organs, where is the utilization of formed elements of blood. It’s the spleen, liver and bone marrow. If the disease affects other organs and systems, in particular, bones, kidneys, lungs, the organs Gradually increase in size, which has a negative impact on General health of the patient.
Genetic component of Gaucher disease
For the first time this pathology described a young French physician Philippe Gaucher in 1882, who studied the tissue enlarged spleen of a dead woman. The doctor was surprised by histological tissue analysis where he found enlarged atypical cells, which subsequently was called Gaucher cells.
In the 30-ies of the last century, it became clear that the increase of cells and tissues in Gaucher disease guilty glucocerebroside, and in 1965 established that the pathology occurs due to the lack of the enzyme glucocerebrosidase.
As you know, an enzyme is a protein structure, and this means that it needs to be encoded by one or more genes in the cell. Analysis of the human genome has established that the gene encoding glucocerebrosidase, is located in the first chromosome. Installed dozens of mutations of this gene that can lead to partial or complete blockage of the production of the enzyme. This disease is inherited in an autosomal recessive manner.
On average, Gaucher disease occurs with a frequency of 1 in 40-60 thousand. However, Ashkenazi Jews the incidence is significantly higher in 1 in every 450 births. This means that in this ethnic group fairly high level of carriers of the disease when one of the chromosomes contains the mutant gene.
As the disease manifests itself
The main symptom in the early stages of the disease splenomegaly (enlarged spleen). In some cases the increase reaches catastrophic performance 5-15 times!
In addition, in this pathology in 1,5-2 times increases the size of the liver (in more severe cases increase up to 3-5 times). Laboratory tests to glucocerebroside show that their norm exceeded 20-300 times.
Due to the abnormally enlarged spleen is the destruction of red blood cells, which leads to the development of anemia. Also develops and thrombocytopenia that can lead to the development of multiple hemorrhages. Against this background, developing and General symptoms such as weakness and fatigue patient.
With the progression of the disease occurs deformity of the bones. When the accumulation of Gaucher cells in bone tissue have pain, inflammation and the risk of bone fractures.
Treatment of Gaucher disease
Doctors and scientists are absolutely convinced that in the near future this disease will be corrected with the help of genetic revision, but until such technology is not available to mankind.
For a long time the treatment of Gaucher disease was limited to the removal of the spleen, which, naturally, led to the development of a number of other pathological changes, in particular the accumulation of waste products of body in other organs and systems, liver and skeletal system.
In 1991 a new era in treatment of this disease. In the U.S., has developed an enzyme alglucerase, which successfully held enzyme replacement therapy. In other words, like insulin in diabetes, in Gaucher disease regularly injected the drug based on a synthetic enzyme, which is included in the macrophage and breaks down glucocerebroside, thus preventing their accumulation in the lysosomes.
One of the mysteries of Gaucher disease time symptoms. In some patients it occurs at a young age and develops so rapidly that leads to death after 2-3 years. In some patients, the disease is found in a ripe old age before these people did not experience any health problems. In this sense, scientists still have much to understand.
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