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Gaucher disease. Causes and clinic of Gaucher disease

Gaucher disease is a hereditary disease in which lipid metabolism in the body is disrupted. This disease is one of the most common among those characterized by lysosomal accumulations associated with the complete absence or deficiency of lysosomal enzymes.

The disease was first discovered in 1882 by the French scientist Philippe Gaucher, who was treating a patient with an enlarged spleen and liver.

Description of the disease

Gaucher disease is recorded extremely rarely: among 100,000 people, only one patient is found. At the same time, in the human body there are specific cells called macrophages, which are responsible for destroying cellular fragments in order to break them down for secondary use. This recycling process can occur within cellular structures called “lysosomes.” Lysosomes contain special enzymes that can break down glucocerebrosidases. In people who are sick with this disease, there is a decrease in this enzyme, which accumulates inside the lysosomes. Against this background, the number of macrophages begins to increase, and their growth progresses. Such formations are called “Gaucher cells”.

Types of Gaucher disease

Photos of patients are presented in the article. In modern medicine, there are three main types of this disease. But, unfortunately, the causes of Gaucher disease have not been fully studied.

The first type is the most common among the others and occurs in approximately 50 people out of 70,000. In some patients, it can proceed calmly, without causing significant symptoms, while in others, very serious disorders may occur, which often become life-threatening. In this case, the process of damage to the brain and nervous system begins.
With the second type of inheritance, Gaucher disease has symptoms of severe neuronopathy. It is extremely rare, occurring in approximately one case per 100,000 people. Symptoms of this type of Gaucher disease are observed already in the first year of life. In this case, the child develops serious neurological disorders. According to statistics, such children do not live to see three years of age.
The third type is characterized by the development of a chronic form of neuronopathy and is as rare as type 2 disease. In this case, pronounced neurological symptoms are observed, but the disease proceeds more calmly. Symptoms appear in early childhood, but, nevertheless, a person can live to adulthood.

Symptoms of Gaucher disease

The clinical picture of this disease is ambiguous. Sometimes it happens that diagnosing the disease is difficult. This is due to the symptoms being too mild. However, even in cases of their particular severity, doctors often find it difficult to make the correct diagnosis due to the rarity of the disease. This is also complicated by the fact that the symptoms of the disease are very similar to the processes of hematological diseases. The symptoms in this case are:

Enlargement of the spleen and liver, which usually provokes severe pain in the abdominal area, general discomfort, and a feeling of false satiety. Sometimes the liver increases in size slightly, but this can be observed when the spleen is removed.
Anemia.
General weakness and fatigue.
Pale skin color.
Thrombocytopenia is a decrease in platelet levels. This often leads to nosebleeds, bruising on the body and other hematological problems.
Sometimes there are cases of destruction or weakening of bone tissue, which can manifest itself in the form of fractures that occur in the absence of injury. There are known cases where Gaucher disease causes the development of a disease such as arthrodesis of the foot and leg.
Growth disturbance in children.

How is Gaucher disease diagnosed?

Diagnostic methods

Among the main methods for diagnosing this disease, there are only three studies that indicate the presence of the disease only in cases where all the results are positive. These methods include:

Blood test. This is one of the most accurate methods for diagnosing this disease, by which the presence or absence of Gaucher enzymes is detected. In addition, the level of glucocerebrosidase in leukocytes and the presence of fibroblasts are determined.
DNA tests. This method is second in popularity after determining the enzyme composition of blood. His results also show a deficiency of the above enzyme, but in addition, also genetic mutations that could trigger the development of Gaucher disease. This method was developed quite recently. It is based on the latest research by biological scientists. Its advantages lie in the fact that this method allows you to determine the disease in the initial stages, sometimes even in the early stages of pregnancy. The carrier of the disease can be identified with a probability of up to 90%.
The third method allows you to analyze the structure of the bone marrow and identify changes in its cells that are characteristic of Gaucher disease. Until recently, such diagnostics were the only method to determine whether a person had such a disease. However, it is very imperfect in the sense that the disease could be diagnosed only in cases where people were already sick. Today it is almost never used in practical medicine.

Acute form of the disease

This form of the disease affects exclusively infants and the process of its development begins in intrauterine life. The characteristic signs of this disease are the following:

developmental delay;
fever;
swelling in the joint area;
cough or cyanosis, which are causes of respiratory failure;
increase in abdominal size;
leaching of calcium from the body;
pale skin;
enlarged lymph nodes;
rashes on the skin of the face;
increased levels of lipids and cholesterol;
thrombocytopenia;
leukopenia;
anemia;
difficulty swallowing;
increased muscle tone;
various paralysis;
blindness;
strabismus;
convulsions;
opisthotonus;
cachexia;
dystrophic changes.

The prognosis for the course of the disease for such infants is extremely unfavorable. As a rule, the patient's death occurs in the first year of life.

Chronic course of the disease

Gaucher disease manifests itself around the ages of 5 to 8 years. Characteristic features are:

splenomegaly;
spontaneous pain in the lower extremities;
possible hip deformities;
change in skin color, pigmentation in the neck and face, as well as palms;
anemia;
leukopenia;
granulocytopenia;
thrombocytopenia;
cholesterol and lipid levels are normal;
content of p-globulins in the blood;
high activity of acid phosphate.

The condition of a sick child may remain in a satisfactory phase for a long time. At a certain point, the general condition may begin to deteriorate, developmental delays become most noticeable, and all the symptoms characteristic of Gaucher disease begin to progress. In addition, there is a significant decrease in immunity.

There is one very important nuance in this disease, which is that the development of the disease depends on the age of the patient. The younger the patient, the more difficult the disease is to treat, and the higher the likelihood of death.

Treatment of Gaucher disease must be comprehensive. It must also be carried out by a qualified specialist.

Treatment of this pathology

Due to the fact that this disease is very rare, its treatment is usually ineffective and is aimed mainly at suppressing symptoms and relieving pain.

Let's look at drugs for the treatment of Gaucher disease.

For therapy, glucocorticosteroids and cytostatics are most often used. Stimulants are widely used in modern medicine:

hematopoiesis;
plasma and blood transfusions;
introduction of sodium nucleinate, as well as a number of vitamins. Children suffering from Gaucher disease are, as a rule, monitored by specialists such as a hematologist and pediatrician. Any preventive vaccinations that are used for healthy children are contraindicated for them.

Features of treatment in adults

For people who develop the disease in adulthood, treatment can include removal of the spleen, orthopedic surgery to eliminate fractures resulting from the development of the disease, and enzyme therapy. The essence of the latter event is that once every two weeks the patient is given injections of a certain drug.

Replacement therapy for this disease

There are also a number of medications that successfully help fight lysosomal disorders in the body. This is replacement therapy, the essence of which is to compensate for the lack of enzymes in the body, or to artificially supplement the missing parts of enzymes. Such drugs are created based on the latest advances in genetic engineering and help replace natural enzymes either partially or completely. A positive result of drug treatment is achieved in the early stages of the disease.

In 1882, medical student Philippe Gaucher drew attention to the condition of his 32-year-old patient - the woman had a greatly enlarged spleen. The patient died of sepsis, and an autopsy and careful examination of the internal organs showed that the cells of the spleen and liver were much larger than normal.

Gaucher then decided that he was faced with a form of spleen cancer - the true cause of the disease, which was later named after this French doctor, became known already in the twentieth century, when scientists managed to isolate glucocerebroside, a fat that accumulates in them in large quantities, from spleen cells . In 1965, it became clear that it accumulates due to the absence of glucocerebrosidase (β-D-glucosidase), the enzyme necessary for its cleavage of glucose from glucocerebroside. It accumulates not only in the spleen and liver, but also in the bones, bone marrow, and kidneys, disrupting their normal functioning.

It's all about mutation

Glucocerebrosidase deficiency is associated with the presence of a specific mutation in the genome. The disease is inherited in an autosomal recessive manner, that is, for the disease to manifest, the mutant allele must be present in both the father and mother.

At the moment, several hundred mutations are known that affect the production of the enzyme - this is associated with the variety of symptoms observed in patients. Enlarged spleen, splenomegaly is the earliest and most common sign of the disease. Gaucher disease affects the musculoskeletal system: patients develop osteoporosis, deformed bones, and suffer from severe chronic bone and joint pain.

Gaucher disease is classified as a fairly hereditary disease - a lysosomal storage disease. “Gaucher disease is a rare disease associated with metabolic disorders in special cell structures - lysosomes. They are involved in the breakdown of complex molecules. In patients with lysosomal diseases, which include Gaucher’s disease, these molecules are not broken down, but accumulate in cells, leading to various disorders,” explains Ekaterina Yuryevna Zakharova, head of the laboratory of hereditary metabolic diseases of the Federal State Budgetary Institution of Medical Genetics Research Center, chairman of the expert Council of the All-Russian Society of Orphan Diseases.

Tablets instead of infusions

About 6 thousand people worldwide live with Gaucher disease - approximately 350 of them live in Russia. After the disease was included in the state program “7 nosologies”, all Russians with this disease were provided with the necessary medications.

For more than a quarter of a century, enzyme replacement therapy—intravenous administration of the missing enzyme, glucocerebrosidase—has been available to those suffering from the most common form of the disease, Gaucher disease type I. Gaucher's disease was the first disease for the treatment of which this approach began to be used - now enzyme replacement therapy is used for other lysosomal diseases and there are already more than ten such diseases.

This therapy does improve the condition of patients, but it is not easy to undergo. Infusions of the necessary enzyme are carried out in a hospital setting - patients are forced to go to the hospital every two weeks throughout their lives. Constant infusions cause the development of phlebitis - inflammatory diseases of the veins - when they occur, it becomes difficult to continue vital treatment.

“In addition to enzymes, they create special “small molecules” that can penetrate the blood-brain barrier, and most importantly, they are produced in the form of tablets, which is much more convenient for patients. And the effectiveness of this treatment is no less! A new approach to the treatment of Gaucher disease, namely the so-called substrate-reducing therapy (therapy aimed at reducing toxic compounds accumulated in cells), already registered in the Russian Federation (INN - eliglustat), allows one to avoid such “costs” of infusion therapy, since the drug is produced in in the form of tablets. This therapy will allow patients to lead a more fulfilling lifestyle,” says Sergei Ivanovich Kutsev, chief freelance geneticist of the Ministry of Health of the Russian Federation, director of the Federal State Budgetary Institution of Medical Genetics Research Center. He also emphasizes that already this year the production of the drug, which is vital for patients, will begin in Russia.

Ekaterina Zakharova adds that the medicine in tablets has already passed clinical trials in our country and can be recommended for the treatment of patients with moderate disease.

“It is quite possible that with the advent of a tablet drug, personalized therapy will be selected for patients with Gaucher disease in the foreseeable future: a combination of ERT and a tablet form. This approach may make it possible to first achieve normal values with infusions and then maintain the condition with tablets; perhaps this approach will be more effective in neurological forms of the disease.”

Gaucher disease usually called a disorder of sphingolipid metabolism, which is a response to a deficiency of the enzyme that destroys glucocerebroside; such a complication can lead to the deposition of glucocerebroside. Symptoms of Gaucher disease most often include hepatosplenomegaly or changes in the central nervous system. In order to correctly diagnose the disease, it is necessary to conduct cytochemical studies of leukocytes.

It is a disease that is not so common; it is transmitted hereditarily when both parents are carriers of the defective gene. Gaucher's disease first appeared on the pages of medical manuals in 1882.

A lack of the enzyme beta-glucocerebrosidase in membrane-enclosed cellular organelles can lead to the formation of a large amount of nutrient medium for microorganisms of this organic substance in the cells of the macrophage system of the whole body, as a rule, this process occurs and develops in the glands, as well as in the cells of the bone marrow and spleen.

To date, science has established three types of Gaucher disease:

Type 1 is most often found in people who have passed puberty, and is also permanent; this type cannot be characterized by the presence of neuronopathy. Type of disease number 1 can be called the most sluggish and common type, in which the central nervous system will not be affected.
Type 2, in which children are the targets, is not so common in science. With this type of disease, as a rule, neurons are affected, which entails almost complete atrophy of the entire nervous system. With this diagnosis, the child dies while still an infant.
Type 3 is usually called “juvenile” in science; in this type, the symptoms of the process are less pronounced, in which case atrophy of neuron cells is inevitable. It is worth noting that type 3 is also quite rare. Scientists characterize this type of disease as a gradual as well as chaotic involvement of the entire nervous system in this process.

The fact that Gaucher disease can exist in different external forms, as well as in conditions in which there is a different internal structure, confirms the diversity of changes in the highly structured glucocerebrosidase gene on chromosome 1. Despite this, diseases of varying degrees of severity can be traced among a given genotype . The main place in the question of the power of transformation is given to a sharp increase in the number of macrophages in organs and tissues, which is a response to the appearance of a large amount of glucocerebroside, however, the methods of its functioning are still not known.

The Gaucher zygote, as a rule, is like an oval and has a size of about 70-80 mm in diameter, as well as a pale cytoplasm. It contains two or more nuclei with increased pigmentation, which are shifted to the periphery. In the middle of these nuclei there are thread-like protein structures that are located simultaneously in relation to each other.

During the development of the disease, beta-glucocerebroside accumulates, which ultimately originates from disintegrated plasmalemmas, tends to become a sediment in membrane-surrounded cellular organelles and form elongated tubes measuring twenty and sometimes forty mm in length; these tubes can be seen when an increase of 2-3 thousand times. Such zygotes can be found in CML, as well as in tumors of the B-lymphocyte system, since as a result of these ailments, an accelerated process of beta-glucocerebroside metabolism is observed.

Symptoms of Gaucher disease

In the normal state, an organic substance is observed that destroys glucocerebroside, which hydrolyzes glucocerebroside, while forming glucose and ceramides. If during the development of the organism there was damage to organic matter obtained at the genetic level, then this can lead to the fact that the cells begin to capture and digest solid particles, thereby creating Gaucher zygotes. Accumulation of these zygotes in spaces
around the vessels in the substance of the human brain provokes the process of replacing dead or replaced neurons with glia cells. There are 3 types, which differ in the pattern of occurrence and spread of diseases of various etiologies, the activity of organic matter, as well as the nature of the manifestations:

Type 1 is characterized by the highest frequency of occurrence - this type is found in 90% of the population (non-neuronopathic).

The activity, which can be called residual, observed in organic matter, has the highest rate. The first manifestations can occur from 2 years to old age. The main symptoms are changes in bone cells, slow development in terms of physiology, delayed activity during puberty, and hemorrhages in the skin. The last symptom, accompanied by nasal hemorrhages, is quite common. After taking an x-ray, doctors usually find that the ends of the long bones have been widened and the bone plate of the oral cavity has become thinner.

Type 2 is characterized by the lowest frequency of occurrence (acute neuronopathic). With this type, a decrease in the residual activity of organic matter is observed. The first serious signs can be detected at an early age - after birth. The main symptoms are rapidly developing neurological disorders: inelasticity, unfortunately, this type in most cases leads to death at the age of about two years.

Type 3 is between the most common and the rarest (subacute neuronopathic). The vital activity of organic matter, as well as the severity of the disease, accordingly, are intermediate between types 1 and 2. The first symptoms of this type can be detected in childhood. Clinical manifestations may vary depending on the variety, and also include incoordination (Ilia), infection of organs and bone tissue (Nib) and degenerative diseases of the central nervous system with corneal opacification (Cs). If with this type the patient survives the teenage stage, in the future he, as a rule, lives for a long time.

Diagnosis of Gaucher disease

Diagnosis of this disease usually involves a cytochemical study of leukocytes. Types, as well as carriage, are usually identified based on analysis of the nature of mutations. Gaucher zygotes have diagnostic value.

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Treatment of Gaucher disease

For types 1 and 3, replacement treatment with special complex drugs using placental or recombinant glucocerebrosidase is recommended; for type 2, treatment, unfortunately, is useless, moreover, it is completely unknown to science and medicine. During treatment, a change in the enzyme occurs for its rapid and timely transport into a membrane-surrounded cellular organelle. Patients treated with special complex medications are prescribed daily monitoring of the level of blood dye, as well as colorless blood cells; constant monitoring of the size of the liver and spleen using CT or MRI; constant monitoring of bone tissue lesions with complete observation of the skeletal system as a whole, dual-energy x-ray absorptiometry scanning or MRI.

As a rule, patients are prescribed the following drugs: Miglustat, which must be taken in certain doses, namely, three times a day, one hundred mg orally, Miglu-stat - this type of medication reduces the concentration of glucocerebroside, and also becomes a kind of solution for patients who, for certain reasons are unable to undergo treatment with enzyme replacement therapy.

It is usually prescribed to patients with anemia, as well as when the number of leukocytes and platelets in the blood decreases, as well as when the spleen increases in size, which begins to cause discomfort.

For thorough treatment of patients with this disease, doctors resort to stem cells, however, this type of treatment is the most dangerous for the health and life of the patient, and therefore is used as rarely as possible.

In our conversation today, we will try to talk in the simplest words about such a disease as Gaucher disease. It is hereditary and disrupts lipid metabolism in the human body. Among lysosomal storage diseases, Gaucher disease is the most common. It is associated with a deficiency or absence of lysosomal enzymes.

This disease acquired its name in 1882. It was described by the French physician Philip Charles Ernest Gaucher, who in this year was the first to describe the disease in a patient with an enlarged spleen and liver. As you remember, at the very beginning of the conversation we mentioned the rarity of this disease. So, in order not to be empty words, we will present these figures. Out of a hundred thousand people, only one is affected by this disease..

The essence of the disease is based on the presence in the human body of special cells called macrophages. They are responsible for the destruction of cellular fragments in order to break them down for recycling. This recycling process occurs inside cellular structures called lysosomes. In turn, they contain a certain enzyme that breaks down glucocerebrosidase. In people who suffer from Gaucher disease, the amount of this enzyme is insufficient and it accumulates inside the lysosomes. In turn, there is an increase in the number of macrophages; their growth is due to the excess content of glucocerebroside. These cells are called Gaucher cells.

Types of Gaucher disease

Modern medicine distinguishes three types of this disease.

Type I (no significant neuronopathy)

It is the most common form of this disease. Occurs 1 in 40 or 60,000 people. Some patients have no symptoms, while others may develop severe or even life-threatening symptoms. The nervous system and brain are affected.

Type II (with pronounced acute neuronopathy)

In contrast to the first, it is extremely rare, namely, only one case per 100,000 thousand population. However, the symptoms are quite pronounced and develop in the first year of life. Its companions are pronounced neurological disorders, as well as other symptoms. In most cases, the life expectancy of the carrier is not more than two years.

Type III (with chronic neuropathy)

Occurs with the same frequency as in the first case. Neurological symptoms are typical for patients, but they are more pronounced than in the second type. Symptoms appear in childhood, but the person lives into adulthood.

Gaucher disease - symptoms

The clinical picture of this disease is ambiguous. There are cases when its diagnosis is quite difficult due to weakened or vaguely expressed symptoms. However, even if they are pronounced, it is extremely difficult for doctors to establish an unambiguous diagnosis. This is primarily due to lack of awareness. It is in such cases that all symptoms are interpreted as symptoms related to hematological diseases. Modern medicine is familiar with the following symptoms of Gaucher disease:

significant enlargement of the liver and spleen.
They are the ones who provoke abdominal pain, general discomfort and a false sense of satiety. However, there are cases of mild expression of liver enlargement, which is observed when the spleen is removed. In some cases, Gaucher disease can lead to liver problems. In turn, changes in the spleen can provoke:

anemia;
weakness;
manifestation of fatigue;
pallor of the skin.

Thrombocytopenia or a decrease in the number of platelets in the blood, which can lead to frequent bleeding from the nose, gums, the appearance, for no apparent reason, of hematomas or other hematological manifestations.

Possible cases of bone weakness, their expressed diseases, as well as pathological fractures that are not the result of injuries. Even arthrodesis of the ankle joint is possible.

Growth impairment occurs among children with Gaucher disease. It is worth noting that the external manifestations of the disease are ambiguous, and the symptoms are always specific and differ in each case. Therefore, these two factors complicate the process of diagnosing the disease.

Gaucher disease - diagnostic methods

There are only three methods for diagnosing this disease.

Blood test. Today it is the most accurate method. This way the Gaucher enzyme is detected. The level of glucocerebrosidase in leukocytes is also determined, and the presence of fibroblasts in culture, which will be the most reliable basis for establishing the correct diagnosis.
DNA analysis. It is the second most popular method, with the help of which both a deficiency of the enzyme glucocerebrosidase and genetic mutations are also detected. Developed relatively recently. Based on the latest advances in molecular biology. Its advantage lies in the possibility of carrying out the earliest diagnosis, or rather at the stage of pregnancy. Using this method, the carrier of the disease is detected with 90% probability. Only with its help can it be possible to predict even the severity of the disease in the future.
The third diagnostic method is based on bone marrow analysis and also provides the opportunity to identify changes in bone marrow cells characteristic of Gaucher disease. Not so long ago it was the only way. However, its flaw was in diagnosing the disease exclusively in people who already had the disease. Today it is practically not used.

Gaucher disease in children

There are two forms:

spicy;
chronic.

Acute form

In this case, only infants are susceptible to the disease. The disease begins in the first months of extrauterine life of the baby and is characterized by:

delay in physical and neuropsychological development;
fever;
significant increase in abdominal volume;
respiratory failure (cough, cyanosis);
swelling of the joints;
decalcification.
swollen lymph nodes (rare);
brown peculiar skin color;
petechial rashes in the facial area (sometimes on other parts of the body);
increased amount of cholesterol and lipids in the blood;
presence (always) of anemia, leukopenia, thrombocytopenia.

Among the numerous neurological symptoms observed:

lockjaw;
difficulty swallowing;
muscle hypertension;
paralysis of the most diverse localization;
opisthotonus;
blindness;
clonic and tonic convulsions;
strabismus.

Diagnosis of the disease occurs by studying the results obtained during a clinical and radiological examination, as well as on the basis of sternal puncture and the presence of Gaucher cells in it:

large;
round shape;
filled with cerebrosides.

The disease progresses quickly and develops:

dystrophy;
cachexia.

The prognosis for such babies is not favorable. Death occurs in the first year of life. In the majority of cases, death occurs in the 2nd or 6th month of the infant’s life from the onset of the disease. The cause of death is always an intercurrent associated disease.

Chronic form

Children aged 5 to 8 years are most often affected. However, it occurs in children of any age group. Characterized by:

early enlarged abdomen or splenomegaly;
spontaneous pain in the legs;
possible flask-shaped deformity of the hip, resembling a “bottle”.
brown skin of the face, palms, neck (with a bronze or ocher-yellow tint);
possible transition of pigmentation to diffuse with the capture of the mucous membrane;
possible hemorrhages of various shapes and sizes;
possible nasal and intestinal hemorrhages.

Regarding the chemical composition of blood, the following are observed:

leukopenia;
anemia;
thrombocytopenia;
granulocytopenia;
normal lipid and cholesterol levels;
increased activity of acid phosphate;
p-globulin content.

For a long time, the general condition of the child remains satisfactory for a long time. Then, a lag in physical development is gradually observed, and all of the listed manifestations of the disease begin to progress. There is a decrease in immunity, and anemia increases. In this case, the prognosis will be determined by the age of the child. The younger he is, the worse his situation becomes.

Gaucher disease and treatment of children

Due to the lack of any drugs, treatment is ineffective. In the case of expressed:

significant bone changes;
silenomegaly;
bleeding;
hemorrhages

splenectomy is used.

Sometimes they resort to the use of glucocorticoids in a dosage of 1 mg. per 1-in kg. body weight per day. It is taken in such doses until a positive effect occurs, followed by a gradual dose reduction. After this course, cytostatics are prescribed. Stimulants are widely used:

blood and plasma transfusions;
hematopoiesis,

and also the introduction:

sodium nucleinate;
vitamins;
saturated fatty acids.

Children should be constantly monitored by a pediatrician and hematologist. They are also contraindicated for any preventive vaccinations.

Gaucher disease and treatment of adults

Not so long ago, treatment was limited to:

removal of the spleen;
elimination of pathological fractures by performing orthopedic operations,

and also many other things that eliminated not the causes of the disease, but only its symptoms. Modern medicine uses a method called enzyme therapy. Its essence consists of injections, which are given once every fourteen days. Prescribed exclusively to those patients who suffer from severe symptoms.

Thanks to numerous developments in this area, there are a number of medications that are successfully used in cases of lysosomal storage diseases through enzyme replacement therapy, which is aimed at replenishing the lack of enzymes in the human body, as well as artificially replenishing the missing enzyme activity. Its artificial substitute is created based on the achievements of genetic engineering and allows you to exactly copy the functions and activities of the natural enzyme. Positive results are achieved through early treatment.

Not long ago, methods for diagnosing the disease were revised. Thus, an enlarged spleen, as well as a low level of red blood cells or red blood cells in the blood, cannot be used as signs that a patient has Gaucher disease. All this leads to erroneous diagnosis.

The disease belongs to lysosomal storage diseases (glucosylceramide lipidosis).

Characterized by deficiency of the enzyme glucocerebrosidase. This leads to metabolic disorders. Lipids are not broken down into re-consumption products, and glucocerebroside accumulates in macrophage cells. They enlarge, take on the characteristic appearance of soap bubbles and settle in the tissues of the body.

Gaucher syndrome develops: the liver, spleen, and kidneys enlarge, and the accumulation of glucocerebroside in the cells of bone tissue and lungs destroys their structure.

What is it?

In short, Gaucher disease is a genetic disease in which fatty substances (lipids) accumulate in cells and on some organs. Gaucher disease is the most common of the lysosomal storage diseases. It is one of the forms of sphingolipidosis (a subgroup of lysosomal storage diseases), as it manifests itself in the dysfunction of sphingolipid metabolism.

The disorder is characterized by fatigue, anemia, low levels of platelets in the blood, and an enlarged liver and spleen. This is caused by a hereditary deficiency of the enzyme glucocerebrosidase, which acts on the fatty acid glucosylceramide. When the enzyme is damaged, glucosylceramide accumulates, in particular in white blood cells, most often in macrophages (mononuclear leukocytes). Glucosylceramide can accumulate in the spleen, liver, kidneys, lungs, brain and bone marrow.

Reasons for development

At the genetic level, mutations occur in the genes that are responsible for the production of the enzyme glucocerebrosidase. This gene with anomalies is localized on chromosome 1. These mutations cause low enzyme activity. Thus, glucocerebroside accumulates in macrophages.

Mesenchymal cells, called Gaucher cells, gradually grow and become hypertrophied. Since modifications occur in these cells, and they are located in the spleen, kidneys, liver, lungs, brain and bone marrow, they, in turn, deform these organs and disrupt their normal functioning.

Gaucher disease is an autosomal recessive disease. Therefore, any person can inherit a mutation of this enzyme with all the features in the same proportion, both from the father and from the mother. Thus, the degree of the disease and its severity will depend on the damage to the genes.

Theoretically, each person can inherit the glucocerebroside gene with lesions or completely healthy. As a result of inheriting a gene with abnormalities, a mutation of this enzyme occurs, but this does not yet indicate a disease. But when a child receives both affected genes, then a diagnosis of Gaucher disease is made. When inheriting one affected gene, the child is considered only a carrier of the disease, so there is a possibility of transmitting this trait, with hereditary pathology, to future generations. Thus, if both parents are carriers of the disease, a child can be born with Gaucher disease in 25% of cases, a carrier child in 50% and a healthy child in 25%.

The frequency of occurrence of this hereditary pathology among ethnic races is 1:50,000, but it is much more often detected among Ashkenazi Jews.

Gaucher disease is also called a storage disease due to a deficiency of the enzyme, which should remove harmful metabolic products from the body, and not accumulate them. As a result of this, these substances accumulate in the macrophages of some organs and destroy them.

Classification and types of disease

The nature of the course of the disease varies in severity. Complications occur in childhood and adulthood. There are three types of disease:

The first non-neuronopathic type. Sociology shows that it is common among Ashkenazi Jews. This pattern is called the Gaucher reaction. The clinical picture is characterized by a moderate, sometimes asymptomatic course of the disease. The psychology of behavior does not change, the brain and spinal cord are not damaged. Symptoms appear more often after thirty years of age. There are known cases of diagnosis in childhood. Timely treatment gives a favorable prognosis.
The second type represents the neuronopathic infantile form and is rare. Symptoms appear in infancy as early as six months. Progressive damage to the child's brain occurs. Death can occur suddenly from suffocation. All children die before reaching two years of age.
The third type (neuronopathic juvenile form). Symptoms have been observed since the age of 10 years. The intensification of symptoms is gradual. Hepatosplenomegaly - enlargement of the liver and spleen - is painless and does not impair liver function. Possible violation of behavioral psychology, the onset of neurological complications, portal hypertension, venous bleeding and death. Damage to bone tissue by Gaucher cells can lead to limited mobility and disability.

Symptoms of Gaucher disease

The clinical picture depends on the type of disease, but there are also general signs of this disease. You can suspect Gaucher syndrome (see photo) based on the following manifestations:

pale skin;
growth disturbance in children;
general weakness;
inflammation of the lymph nodes;
enlarged liver and spleen;
fractures in the absence of injuries;
spontaneous nosebleeds;
hemorrhagic stars on the skin.

Gaucher syndrome does not depend on the gender of the child. In addition, the symptoms of the disease often resemble the clinical picture of hematological pathologies. This makes diagnosing the disease difficult.

Characteristic signs of different forms of Gaucher syndrome:

Gaucher disease in children

Symptoms may begin to appear at different ages. The second type of disease often manifests itself at the age of six months. Patients in this case live up to 1-2 years. The third type is typical for children 2-4 years old, although it is sometimes observed in adolescence. The same applies to the first form. It can appear both in early childhood and adolescence. Symptoms of Gaucher syndrome in children:

poor ability to suck and swallow;
eye movement disorders;
convulsions;
breathing problems;
whooping cough;
yellow-brown skin pigmentation.

Diagnostics

Collecting anamnesis and complaints of the disease (clarification of the time of appearance of the first symptoms of the disease, how they progressed over time).

The disease can be suspected if an enlargement of the liver and spleen is accidentally detected (for example, according to ultrasound), suppression of the hematopoietic system (changes in blood tests: decreased levels of hemoglobin, platelets, the appearance of atypical blood cells), and the appearance of symptoms of bone damage.

At the next stage, special studies are carried out to confirm the diagnosis:

Enzyme analysis - determination of the level of enzyme (glucocerebrosidase) in leukocytes and skin cells, which makes it possible to establish a diagnosis with absolute accuracy;
biochemical blood test (decreased β-glucocerebrosidase activity, increased chitotriosidase levels);
bone marrow examination (presence of characteristic Gaucher cells);
molecular studies at the gene level (detection of genetic disorders);
radiography and computer diagnostics (magnetic resonance imaging) of bones, since there may be areas of lower density that have specific signs for this disease.

Third type of Gaucher disease

How to treat Gaucher disease?

Specialized care for patients with the first and third types of the disease is aimed at eliminating symptoms and compensating for the primary genetic defect - increasing the amount of the missing enzyme, increasing the catabolism of glycosphingolipids. With type 2 pathology, therapeutic measures are not effective enough; doctors’ efforts are reduced to alleviating clinical manifestations - pain, cramps, respiratory disorders.

The general scheme includes the following areas:

Enzyme replacement therapy. The main treatment method is lifelong enzyme replacement therapy (ERT) using recombinant glucocerebrosidase. The effectiveness is quite high - the symptoms are completely relieved, the quality of life of patients increases. ERT is appropriate for the third and first types of the disease. The drugs are administered intravenously. Frequent infusions sometimes cause inflammatory diseases of the veins (phlebitis).
Substrate-reducing therapy. This direction is new in the treatment of Gaucher disease and is relatively widespread in the USA and European countries. Aimed at reducing the rate of production of the substrate glycosphingolipids and accelerating the catabolism of accumulating macromolecules. The drugs used are specific inhibitors of glucosylceramide synthase. The method is indicated for type 1 disease with mild to moderate symptoms.
Symptomatic therapy. In cases of osteoporosis, complex therapy is prescribed, including taking calcium-containing medications, vitamin D and following a diet enriched with calcium. These measures can slow down bone loss, increase bone strength, and prevent fractures. For skeletal complications, analgesics (NSAIDs) and antibacterial therapy are used. Symptoms of neurological disorders can be relieved with antiepileptic drugs, nootropics, and muscle relaxants.

Prevention

The only method of preventing Gaucher disease is medical genetic counseling. If a family has a child suffering from this disease, the presence of glucocerebrosidase in the cells of the amniotic fluid is determined during subsequent pregnancies. If there is a deficiency of this enzyme in the fetus, doctors recommend termination of pregnancy.

Forecast

With the first type of disease, early diagnosis, and timely initiation of replacement therapy for Gaucher disease, positive dynamics are possible. The second type of glucocerebrosidosis is the most unfavorable, as it is more severe. Sick children usually do not live more than two years. The third form of Gaucher disease, with timely diagnosis and adequate treatment, allows maintaining the patient’s vital functions. Otherwise, he dies quite quickly from complications that develop.