Thalassemia treatment. How to treat beta thalassemia minor. Genetic variants of alpha thalassemia

Currently, there are a huge number of hereditary diseases that a child receives along with genes from his mother or father. For some to manifest, it is necessary that both parents pass on the defective gene to their child. Thalassemia is one of these diseases. Few people know what kind of disease this is. In our article we will try to figure this out.

What is thalassemia

This is not even one, but a whole blood group that has recessive inheritance. That is, the child will receive it if both parents pass on the diseased gene to him. In this case, they say that there is homozygous thalassemia. The disease is characterized by disruption of the production of hemoglobin, which plays a major role in the transport of oxygen throughout the body.

Hemoglobin is a protein that has a protein part and a pigment part. The first consists of polypeptide chains: two alpha and two beta. Failure can occur in any of them, hence alpha thalassemia and beta thalassemia.

Impaired hemoglobin synthesis leads to a reduction in the lifespan of red blood cells, and this entails damage to cells and tissues. This process triggers a whole chain of reactions leading to the formation of various pathologies in the body.

Classification of the disease

There are several approaches to classifying this disease. If we consider in which circuit the failure occurred, we can distinguish:

• alpha thalassemia;
• beta thalassemia;
• delta thalassemia.

In each case, the severity of symptoms may vary significantly. Taking this into account, we distinguish:

• light form;
• average;
• heavy.

Depending on whether the child received the gene from both parents or from one, the disease is divided into:

1. Homozygous, in this case the diseased gene passes from mom and dad. This form is also called thalassemia major.
2. Heterozygous. Inherited from only one of the parents.

All varieties are characterized by their symptoms and severity.

Causes of the disease

Each disease has its own causes; thalassemia is also formed under the influence of genes that the child receives from his parents. This genetic disease is particularly complex, but it is also the most common in the world.

Thalassemia is inherited in a recessive manner through the autosome of the parents. This means that the probability of getting sick is 100% for those who received defective genes for this trait from their mother and father.

The disease develops when a mutation occurs in the genes that are responsible for the synthesis of hemoglobin. The alpha form of this disease is quite common in the Mediterranean and Africa. Some people associate thalassemia with malaria, as these areas often experience outbreaks of the disease.

The blame is attributed to the fact that a mutation occurs in genes and thalassemia develops; the photo demonstrates that a large number of patients are found in Azerbaijan, approximately 10% of the total population. This confirms that the prevalence of the disease is associated with mutations, and climatic conditions also influence the mutation process.

Symptoms of thalassemia major

If a child develops homozygous or thalassemia major, symptoms begin to appear almost immediately after birth. These include:

If a child is diagnosed with thalassemia, the symptoms are pronounced, then there is a high probability that he will not live to see his second birthday.

Symptoms of Thalassemia Minor

When the pathology is inherited from only one of the parents, we can talk about thalassemia minor or heterozygous. Since there is a second healthy gene in the genotype, it significantly smoothes out the manifestation of the disease, and symptoms may not appear at all or give a smoothed picture.

Thalassemia minor has the following main symptoms:

1. High and rapid fatigue.
2. Reduced performance.
3. Frequent dizziness and headache.
4. Pale skin with signs of jaundice.
5. The spleen may also be enlarged.

Despite the smoothed symptoms, the danger lies in the fact that the body’s susceptibility to all infections greatly increases.

Diagnosis of the disease

Medicine has the opportunity to make a diagnosis of thalassemia at the early stages of development; diagnosis is carried out on the basis of laboratory blood tests. They immediately show that hemoglobin has a disturbed structure. You can even determine which of the chains there are deviations.

In young children, the signs of thalassemia appear quite clearly, so there is usually no difficulty in making such a diagnosis. Parents, before deciding to have a child, should undergo examination, especially if there is a carrier of the gene or a patient in the family.

It is possible to make a diagnosis of thalassemia already in the early stages of pregnancy; amniotic fluid is taken for analysis and examined. It will always contain fetal red blood cells, upon examination of which the presence of pathology can be determined.

Early diagnosis is very important because it is possible to begin treatment without waiting for the birth of the child, which will give the most effective result.

Beta thalassemia

If the beta variety of the disease is formed, then the synthesis of hemoglobin beta chains is disrupted in the body. They are responsible for the production of hemoglobin A, which in an adult makes up 97% of the total number of molecules. If you look at beta thalassemia - what it is, then we can say, based on a blood test, that there is a decrease in the number of beta chains, but their quality does not suffer.

The reason is that they disrupt the functioning of the genes responsible for the synthesis of chains. It has now been established that there are not only mutations that cause disturbances in the functioning of genes, but there are also some sections of DNA that affect the manifestations of these mutations. As a result, it turns out that in people with the same mutations in the genes responsible for hemoglobin synthesis, the degree of manifestation of the disease can vary greatly.

Types of beta thalassemia

The clinical picture of the disease can be different, depending on this, beta thalassemia is divided into several groups. Not everyone is familiar with the concept of thalassemia; that this disease depends on many genetic factors is also not known to everyone.

There are several gene states that control the production of beta chains:

1. Normal gene. It is in this state that it is found in all healthy people.
2. A gene almost destroyed by mutation. The beta chain is not synthesized at all.
3. A partially damaged gene can only partially perform its job, so chain synthesis occurs, but in insufficient quantities.

Taking all this into account, the following types of thalassemia are distinguished:

Alpha thalassemia

In addition to beta, hemoglobin also contains alpha chains. If their synthesis is disrupted, then we can talk about a form such as alpha thalassemia. The disease is manifested by the formation of only the beta chain, and this risks the fact that hemoglobin of this structure will not be able to fulfill its main purpose - to carry oxygen.

The manifestations of the disease will depend on the severity of the mutation of the genes that control the synthesis of alpha chains. This process is usually under the control of two genes, one the child receives from the mother and the other from the father.

Types of alpha thalassemia

Depending on the degree of gene mutation, this form of the disease is divided into several groups:

If you have a mild form of alpha thalassemia, treatment may not be necessary, but with a severe form you will have to be under the supervision of doctors all your life. Only regular courses of therapy can improve a person’s quality of life.

Treatment of thalassemia

We figured out what kind of disease thalassemia is. Now we need to focus on treatment. It can be noted that therapy is aimed at maintaining hemoglobin at the required level and eliminating the heavy load on the body from large amounts of iron. Treatment methods also include the following:

In addition to the listed treatment methods, symptomatic therapy is also carried out, which alleviates the patient’s condition.

Disease prevention

For doctors and geneticists, if there is a diagnosis of thalassemia, it is clear that it is not curable. We have not yet found ways and methods to cope with this disease. But there are still measures to prevent it. The following preventive measures can be mentioned:

1. Carrying out prenatal diagnostics.
2. If both parents have this disease, then it is imperative to diagnose the fetus in order to identify this pathology. In some cases, it may be necessary to terminate the pregnancy.
3. If you have relatives in your family with this diagnosis, it is advisable to visit a geneticist before planning a pregnancy.

Every organism contains a huge number of mutating genes; it is practically impossible to predict where and when a mutation will appear. This is why genetic consultations exist to help married couples understand their ancestry, or rather, diseases that are passed on from one generation to another.

Prognosis for patients with thalassemia

Depending on the severity and form of the disease, the prognosis may vary. Patients with thalassemia minor live a normal life, and its duration is practically no different from the life expectancy of healthy people.

With beta thalassemia, a small proportion of patients survive to adulthood.

The heterozygous form of the disease practically does not require treatment, but with the homozygous, and even severe form, it is necessary to undergo regular blood transfusions. Without this procedure, the patient’s life is almost impossible.

Unfortunately, thalassemia is currently one of those diseases that science has not yet learned to cope with. You can only keep it under control to some extent.

Medicine knows many diseases of a genetic nature that develop as a result of a peculiar “confluence” of circumstances. When both parents who carry certain abnormal genes pass on a disease to their child, it is called “genetic.” Thalassemia is such a disease.

What is thalassemia

Thalassemia is a genetic disease also called hemoglobinopathy. The disease is characterized by a violation of the synthesis of one of the components of hemoglobin - the protein part.

Hemoglobin (Hb) is the main component of red blood cells - erythrocytes. The main function of blood cells is to carry out the respiratory function of the body by transporting oxygen (O2) through the circulatory system. Also, red blood cells deliver “waste” carbon dioxide back to the lungs for removal from the body.

The structure of the hemoglobin molecule allows for the transport of gases, however, anomalies in its structure lead to disruption of this function.

Hemoglobin consists of two parts: the protein component and the pigment part. The polypeptide chains that form globin (the protein component) consist of two parts: two alpha polypeptide chains and two beta chains. Thus, we get four components, the coordinated work of which allows the red blood cell to perform its functions.

The genetic disease is caused by disturbances in these chains. Failures in α-components lead to the development of the disease alpha thalassemia. And disturbances in the β-chain provoke the occurrence of beta thalassemia.

In both types of disease, the process of hemoglobin synthesis is distorted, which leads to short-lived activity of red blood cells. As a result, the supply of oxygen to the cells and tissues of the body is disrupted. Oxygen starvation develops. The situation is extremely dangerous and provokes the occurrence of pathologies in human organs and tissues.

Locations of the abnormal gene

Depending on the location of the failure, several types of disease are distinguished:

• Alpha thalassemia, which provokes a disorder in the synthesis of α-chains;
• Beta thalassemia;
• Delta thalassemia.
• γ-thalassemia;
• Thalassemia, provoked by a violation of the very structure of hemoglobin.

The most common diagnosis is beta thalassemia. The type of disease is divided into homozygous and heterozygous. Based on the severity of symptoms, beta thalassemia is divided into three forms:

• big;
• small;
• intermediate.

Homozygous thalassemia, or thalassemia major, develops if both the father and mother of the child were carriers of the defective gene. It is also called Cooley's anemia. By the first year of life, a child with a similar gene exhibits a number of symptoms.

Heterozygous thalassemia is caused by the presence of an unhealthy gene in only one of the parents. The disease is called “minor” because of its insignificant manifestation and ease of progression. It happens that the symptoms are so mild that they remain practically unnoticed throughout life.

Thalassemia intermedia is characterized by a non-classical course of homozygous thalassemia, in which obvious signs such as severe hemolytic anemia are absent. A person can do without blood transfusions.

Causes of severe form

The occurrence of beta thalassemia leads to the fact that “incorrect” beta globin predominates in the human blood, resulting in a decrease in the production of beta chains. The lack of these chains provokes the appearance of an excessive amount of alpha chains, which have a detrimental effect on the formation and further viability of red blood cells.

In the human bone marrow, most young blood cells die, and those that were able to survive and fully enter the bloodstream are at risk of destruction. Incomplete hemoglobin in such blood cells is weak and leads to the vulnerability of red blood cells. Also, such blood cells have a weakened membrane - a membrane that quickly collapses. This process is called hemolysis and leads to homolytic anemia.

Constant hypoxia of the body leads to developmental delays in the sick child.

Homozygous thalassemia is divided into three stages depending on the nature of the symptoms and the severity of the course:

• A severe form of the disease is diagnosed early. Pronounced symptoms contribute to this. Most sick children do not live more than one year.
• The moderate form is characterized by less aggressive symptoms, which allows the patient to live on average up to eight years.
• The form, called the mildest, allows a person to survive to adulthood, however, the prognosis still remains disappointing.

Homozygous thalassemia results in the body's inability to produce hemoglobin alpha chains, resulting in fetal hemoglobin not being synthesized in the fetus. This form of the disease is incompatible with life and leads to fetal death or the development of dropsy, which leads to termination of pregnancy.

Types of disease in violation of beta chains

The genes that control the production of beta chains can be in different states:

• Normal healthy gene. In healthy people, it is normal, which ensures the production of correct hemoglobin chains.
• Gene with partial deviations. This pathology allows the body to produce normal hemoglobin, however, it is produced in insufficient quantities.
• The gene is distorted so much that it completely prevents the formation of beta chains.

Depending on the extent of the disease, the following types of beta thalassemia are distinguished:

• Minor thalassemia. In this type of disease, only one gene is damaged. There are practically no symptoms. Slight anemia may occur. Apart from anemia, a person does not complain about his health.
• With a more serious pathology of the gene responsible for the synthesis of beta chains, thalassemia intermedia is observed. As a result of disruption of the hemoglobin production process, red blood cells are formed either underdeveloped or small in size. Blood transfusions are not necessary, however, the subsequent condition of the body directly depends on its ability to live with low hemoglobin levels.
• Beta thalassemia type "major" is characterized by a violation of all genes responsible for the synthesis of beta chains. Patients with this type of disease require regular blood transfusions. This procedure allows the patient to live.

Symptoms of beta chain disorder

Homozygous thalassemia is diagnosed either immediately after the birth of a child, or during the first 10-12 months of life. Symptoms of the disease rarely go unnoticed until the beginning of the second year.

However, in most cases, developmental disorders become widespread, which becomes the reason for diagnosing thalassemia.

Thalassemia is diagnosed if the following symptoms are present:

• A sick child has a deformation of the skull. The head has a square, tower shape.
• The jaw is large and protruding.
• General features resemble the Mongoloid type.
• The eyes, on the contrary, are small.
• The bridge of the nose is set deep, almost flattened. The nose is saddle-shaped. The nasal septum expands over time.
• Malocclusion is often observed.
• The skin has an unnatural color - yellowness of the skin is caused by anemia. Gray color of the dermis is also found.
• Hematopoiesis that occurs in the liver and spleen leads to an increase in these organs. When blood cells break down, hemosiderin is formed, which accumulates in tissues.

• The level of immunity is very low. Children suffering from homozygous thalassemia are prone to many diseases as the body's defense function is missing. With a mild form of the disease, children survive to adolescence, however, they lack secondary sexual characteristics or their development is delayed.
• Growth retardation is caused by a violation of the structure of the tubular bones. As a result of pathology, fractures may occur.
• Synovitis of the joints may occur.
• As a result of the disease, numerous ulcers of the lower extremities form.
• Hemosiderosis leads to liver cirrhosis, as well as to pathologies of the pancreas, against which diabetes mellitus develops. Heart failure also results from excess hemosiderin.
• Due to decreased immunity, the patient may suffer from pneumonia, as well as intestinal infections and sepsis.
• The amount of hemoglobin decreases to 30-50 g/l.
• As a result of elevated iron levels, cardiosclerosis develops.

Symptoms according to the heterozygous type of the disease

With the heterozygous type of thalassemia, it is not always possible to determine the presence of the disease. This is due to sluggish symptoms, usually of a general nature. The symptoms often resemble a number of other diseases, although patients often do not attach any importance to them. This type of disease can provoke symptoms similar to other diseases, however, the real cause is thalassemia, the diagnosis of which requires testing.

Symptoms characteristic of heterozygous thalassemia:

• The patient complains of weakness and increased fatigue. Decreased performance and frequent apathies are possible.
• Pale skin. There may be a slight manifestation of scleral icterus.
• Examination reveals a slight enlargement of the spleen.
• A blood test can show radically different results. Normal hemoglobin levels are possible, but most often they are low. Anemia is hypochromic in nature. But the decrease in color index is most often insignificant.
• Targeted blood cells are common. This may be a consequence of iron deficiency anemia or lead intoxication.

When diagnosing a disease, an important indicator is the presence of the disease in the patient’s family members.

Alpha chain disorder

Alpha thalassemia is diagnosed when the synthesis of hemoglobin alpha chains is impaired. An additional beta chain appears in their place. As a result, the main function of hemoglobin is disrupted: blood cells become unable to transport oxygen to cell tissue.

Symptoms depend on the degree of mutation of the genes that the child receives from his parents. Genes responsible for creating alpha chains can interfere with their formation to varying degrees.

Depending on the degree of gene mutation, alpha thalassemia disease is divided into forms:

• With pathology of only one region of the gene, the symptoms are mild. The disease may go unnoticed.
• The defeat of two loci results in the formation of red blood cells that are excessively small in size and leads to a decrease in hemoglobin levels. Loci can be affected either in one gene or in two different ones.
• The pathology of three loci leads to the impossibility of high-quality transport of oxygen through the circulatory system. An increase in the size of the spleen is often noted.
• If all gene loci are affected, the synthesis of alpha chains is completely disrupted in the fetus, which leads to death in the womb or death immediately after birth.

Diagnosis of the disease

The main criterion when determining the presence of thalassemia in a patient is the test results.

Diagnosis of thalassemia is based on the blood picture:

• Most forms of alpha thalassemia are characterized by a decrease in hemoglobin levels. The red blood cell count is in the range of 50-30 g/l, which is below normal.
• The color indicator in the blood test is at 0.5, which is critical.
• Anisocytosis is a pronounced change in blood cells, target-like red blood cells and basophilic granularity.
• The blood cells themselves are hypochromic.
• An increased level of reticulocytes is observed.
• Biochemical blood parameters are also elevated. High iron levels can damage the heart muscles.
• Exceeding the level of fetal hemoglobin in blood cells (sometimes up to 90%).

Treatment of hemoglobinopathy

Treatment of thalassemia depends on its type and the nature of the disease.

Thalassemia major refers to excessive hematopoiesis in bone tissue. With this type of disease, the patient becomes completely dependent on blood transfusions.

Treatment is carried out in three stages. At the initial stage, transfusions are carried out at an accelerated pace: in 14-21 days the patient undergoes from eight to ten transfusions. The result of this treatment is an increase in hemoglobin to 120-140 g/l.

The next stage is to reduce the frequency of transfusions. The procedure is carried out every three weeks in the amount of 20 milliliters per kilogram of weight. The goal of this process remains to maintain hemoglobin levels within 100 g/l. Thus, the symptoms caused by the disease “Cooley's anemia” are suppressed.

Then the frequency of transfusions is determined depending on the patient's condition and the course of the disease. This procedure not only improves overall well-being, but also has a positive effect on the skeleton, the condition of the spleen and has a beneficial effect on the development of the child.

A serious disadvantage of this method of treatment is the accumulation of iron-containing pigment in the body. The situation leads to an enlarged liver, as well as a disruption in the absorption of glucose by cells.

To eliminate the problem, treatment includes the drug Desferal, which is administered intramuscularly in a certain amount. It depends on how much blood the patient is transfused, as well as the age of the child. Often the medicine is combined with small doses of ascorbic acid.

In most cases, the described methods lead to an improvement in the condition; however, recently, bone marrow transplantation to the patient has been widely practiced, which also has positive results.

Treatment of heterozygous type

For heterozygous thalassemia, emergency treatment is not required. Since most often the hemoglobin level is within the normal range, transfusions are not needed for such patients.
The spleen rarely increases to a critical size, so cases of organ removal are rare.

Desferal is used to treat elevated iron levels. The drug also helps prevent siderosis.

Siderosis is a disease characterized by sedimentation in the lungs as a result of elevated iron levels.

A decrease in hemoglobin levels is observed with immunity disorders, namely with its decrease. Pregnant women are also at risk. Folic acid is prescribed as treatment, the dosage of which is determined individually.

The use of iron-containing drugs is extremely dangerous for patients with this disease. The introduction of such drugs into the body can cause death in a patient who previously felt normal.

With thalassemia, doctors: a therapist and a hematologist are involved in diagnosing and prescribing treatment.

Often children can inherit from their parents not only characteristic traits and positive qualities, but also a hereditary disease.

The likelihood of getting any hereditary disease depends directly on the presence of defective genes in the parents. Thalassemia refers specifically to such genetic diseases that are inherited from parents to their children.

What is thalassemia

Thalassemia is a group of genetic blood diseases (ICD 10 code – D56), which causes an abnormal mutation of red blood cells, resulting in a disruption in the transport of oxygen molecules to the cells and tissues of the body.

Hemoglobin makes up the bulk of the blood cell and is the main substance for binding oxygen molecules and moving them throughout the body. With this disease, the entire process of synthesis of hemoglobin polypeptide chains is disrupted, which leads to defective and short-lived red blood cells.

As a result of such changes, there is a lack of oxygen in the tissues of the body, which leads to pathology and deterioration in the functionality of human organs.

The carriers of this disease are defective genes that are responsible for the construction of hemoglobin. Their inferiority lies in the impossibility of compiling the correct set of amino acids in the chromosomal chain.

Forms of thalassemia

Polypeptide chains are responsible for the performance of hemoglobin: alpha (α) and beta (β). Impaired synthesis in any of these chains can result in abnormal red blood cells.

There are two types of this disease based on the irregular abnormality of the polypeptide chains:

1. alpha thalassemia (ICD 10 code – D56.0);
2. beta thalassemia (ICD 10 code – D56.1).

And also any type of thalassemia may differ in the way the mutant gene is acquired from the parents. Heterozygous thalassemia is acquired from only one parent and is usually a mild form of the disease. Homozygous thalassemia is acquired from both parents and can have a moderate or severe form of the disease.

Alpha thalassemia

Four genes (two genes from each parent) are responsible for building the alpha chain.

The severity of thalassemia disease will depend on the number of transmitted “sick” genes:

1. Mutation in one gene. The disease is not detected due to the absence of clinical manifestations. A person with this form of thalassemia can only be a carrier, which will lead to the likelihood of transmitting the disease to their children in the future.
2. Mutation in two genes. Thalassemia minor is characterized by a low level of hemoglobin in the blood and small red blood cells. May be acquired from one or both parents.
3. Mutation in three genes. The average form of the disease has a clear violation of the oxygen supply of the body. Various pathologies can occur in the systems and organs of the human body.
4. Mutation in four genes. Major form of the disease or alpha thalassemia major. With this anomaly, the alpha chains responsible for the transfer of oxygen molecules into cells are completely absent. This form of the disease leads to the death of the child in the womb or in the first days after birth.

Beta thalassemia

Only two genes (one from each parent) are involved in creating the beta chain in hemoglobin. When a mutation occurs in one or two genes of this chain, beta thalassemia appears.

There are three forms of this type of disease:

1. Minor or minor form of thalassemia occurs when there is a single mutant gene. It is characterized by a subtle decrease in beta chains, which affects the absence of external signs of the disease.
   For blood tests small red blood cells are detected. A person with this form of the disease lives a relatively healthy life.
2. Intermedia or thalassemia intermediate form is formed by a slight mutation of two genes. Significant damage to the beta chains occurs, which affects very low hemoglobin levels and the presence of a large number of underdeveloped red blood cells. Without treatment, the moderate form usually becomes severe.
3. Major or major form of thalassemia(Cooley's anemia) occurs with a complete mutation of both genes responsible for beta chains. This form requires constant blood transfusions to maintain hemoglobin levels.

Symptoms

In forms of thalassemia minor and major, symptoms manifest differently. According to the method of acquisition, thalassemia minor is classified as heterozygous, that is, the thalassemia gene is transmitted from one parent. In this case, due to the healthy gene from the second parent, the entire overall picture of the disease will be slightly noticeable.

The main symptoms of the minor form include:

• general fatigue, lethargy and weakness;
• frequent headaches and dizziness;
• pallor and yellowness of the skin;
• accumulation of gases, flatulence;
• high susceptibility to viral and intestinal infections;
• possible enlargement of the spleen and liver upon palpation and ultrasound diagnostics.

Moderate and severe forms of thalassemia are classified as homozygous, since defective genes are received from the father and mother at once.

Symptoms for these forms of the disease are pronounced:

• tower-shaped skull;
• formation of Mongoloid facial features;
• enlargement of the upper jaw and expansion of the nasal septum throughout the course of the disease;
• yellowness and pallor of the skin. Also read our article about.
• mental and physical developmental delays are observed;
• formation of bone growths on the feet;
• enlargement of the spleen and liver due to lack of oxygen;

Children with severe thalassemia rarely exceed the five-year mark.

During the transition to adolescence, patients experience additional symptoms:

• frequent bone fractures;
• frequent lung infections;
• sepsis due to contact with infection
• delayed sexual development.

Diagnostics

Modern medicine is able to diagnose this blood disease in the early stages if the diagnosis is carried out correctly.

The first step is timely genetic consultation before planning pregnancy to determine the heredity of thalassemia in future parents. Prenatal diagnosis is possible as early as the eleventh week of pregnancy. Early detection of the disease will help to begin to fight thalassemia in advance.

Sometimes a family history and external examination of the patient allows one to suspect a blood disease in the early stages.

To confirm the diagnosis and begin treatment, the following tests are prescribed for thalassemia:

1. general blood test - checks the level of hemoglobin, the size and shape of red blood cells, the presence of reticulocytes.
2. blood biochemistry - checking bilirubin levels, iron concentration, ability to bind iron.
3. PCR – detection of a defective thalassemia gene in the chromosome. Allows you to definitively confirm or reject the diagnosis of thalassemia.
4. Ultrasound diagnostics - the size of the liver, spleen and the presence of bilirubin stones are examined.
5. bone marrow puncture - the composition and nature of the malfunction of the hematopoietic system.
6. X-ray examination - detection of defects of the skeleton and bone tissue.
7. specific blood tests to determine damage to the circulatory system.

Causes of the disease

• Thalassemia is the most complex hereditary disease, since it is transmitted from parents to children through defective genes that have undergone mutation. Sometimes parents, being carriers, may not be aware of the existence of this disease in their blood. But thalassemia can fully manifest itself in the genes passed on to children.
• If you have the wrong genes hemoglobin synthesis is disrupted in chromosomes, which leads to loss of functionality of red blood cells.
• Foci of spread This disease occurs mainly in the Mediterranean, the Middle East and Central Africa, and is extremely rare in Latin America.
• Occurrence of a primary mutation parent gene is due to Plasmodium falciparum. It has been scientifically proven that it is Plasmodium, when it enters the human blood, that has the main influence on the mutation of genes in the sixteenth and eleventh pairs of chromosomes, which are responsible for the creation of alpha and beta chains.

Treatment

Thalassemia is still one of the rare treatable diseases. This is primarily due to the poor effectiveness and complexity of the treatment method.

With thalassemia minor, no special treatment is required, but there is an action plan to maintain the patient’s moderate condition:

1. Regular collection of blood tests to monitor hemoglobin, red blood cells and iron.
2. Compliance with the recommended lifestyle and nutrition.
3. Reducing iron levels in the human body using food and medicine.

For moderate and major forms of thalassemia, a number of treatment measures are being developed:

What is the danger of the disease

1. In a mild form of this disease the patient is exposed to minimal danger. Since the disease is practically asymptomatic and does not have serious consequences. The only danger is the subsequent transmission of the abnormal thalassemia gene to a future generation.
2. For thalassemia major There is a high mortality rate, especially among newborn patients. In mature and adolescent patients, there is a risk of developing additional serious diseases such as cancer, sepsis, and infections.

Thalassemia prognosis

For patients with thalassemia, the prognosis depends on the severity of the disease:

• With thalassemia minor people often live full, long lives. The difference between such a patient and a healthy person is weaker immunity to various infections.
• Patients with severe thalassemia have a separate way of life. In newborns with this disease, all symptoms appear in the second year of life. People with thalassemia require regular blood transfusions to keep the body functioning. Often the consequences of thalassemia are diabetes, liver cirrhosis, myocardial infarction, and severe joint diseases.
• When appearing in a family history This disease poses a risk of further spread and infection of thalassemia in all subsequent generations.

Prevention

The main goal of prevention is to identify the risk factor for inheriting thalassemia.

There is a set of measures aimed at preventing and preventing this disease:

1. Prenatal diagnostics and genetic consultation, which identify the predisposition of parents and the unborn child.
2. Prenatal diagnosis. It is carried out when an abnormal gene is detected in one or both parents. Sometimes the result of such a diagnosis can be a planned termination of pregnancy.
3. Constant monitoring of patients diagnosed with thalassemia by geneticists, hematologists and therapists.
4. Patients with thalassemia are required to constantly follow a regimen that helps avoid infections.

Every person who does not know his family history is required to undergo a genetic test in advance to detect thalassemia in the blood. It is important to know that this disease is not acquired during life, the child is already born with thalassemia in his genes.

Accumulating in the skin and mucous membranes ( oral mucosa, conjunctiva of the eye), bilirubin gives them a characteristic yellowish tint. The presence of jaundice is typical for severe forms of the disease and is an unfavorable prognostic sign.

Enlarged spleen ( splenomegaly)
The spleen is the main organ responsible for removing old and damaged blood cells from the bloodstream. In thalassemia, the main number of red blood cells formed in the bone marrow and released into the systemic circulation are small in size and have a deformed surface. They cannot pass through the capillaries of the spleen, as a result of which they are retained and accumulate in it in large quantities, causing the organ to enlarge.

With prolonged splenomegaly, not only deformed red blood cells, but also other normal blood cells begin to be retained in the spleen ( platelets, leukocytes). They cannot pass through the capillaries of the organ, since they are completely filled and blocked by red blood cells. The result of this process is the development of hypersplenism, a pathological process characterized by the destruction of normal blood cells in the enlarged spleen.

Urate diathesis
One of the substances released into the bloodstream during the destruction of blood cells is purine. It is part of nucleic acids - DNA ( deoxyribonucleic acid) and RNA ( ribonucleic acid), which are part of the genetic apparatus of cells. Once purine enters the bloodstream, it is transported to the liver, where it is converted into uric acid.

With an increase in the concentration of uric acid and its salts ( urates) in the blood, they can form crystalline compounds that settle in various tissues of the body, causing their damage.

The accumulation of uric acid and its salts can manifest itself:

• Damage to joints. As a result of the deposition of uric acid salts on the articular surfaces of the bones, their deformation occurs, which is manifested by pain during movement. With a long course of the disease, deformation of the articular cartilages and limited range of motion in the affected joints develop.
• Kidney damage. Urate accumulates in the kidney tissue and destroys it, which can lead to kidney failure.
• Formation of urate stones. Crystals of uric acid salts can accumulate and form stones in the kidneys or bladder. Clinically, this is manifested by pain in the lumbar region, difficult and painful urination, as well as a tendency to infections of the genitourinary organs.

Diagnosis of thalassemia

The main methods used in the process of diagnosing thalassemia are:

• additional laboratory tests;
• X-ray examination;
• ultrasonography;
• bone marrow puncture;
• polymerase chain reaction ( PCR).

General blood analysis

Blood collection procedure
Blood is taken in the morning, on an empty stomach. A nurse collects blood for analysis. To prevent infection of the skin of the fingertip ( most often the nameless one on the left hand) is treated with a cotton swab soaked in 70% alcohol, after which a special disposable game is used to make a puncture to a depth of 2 - 4 millimeters. The first drop is removed with a cotton swab, after which several milliliters of blood are drawn.

Blood test in the laboratory
Part of the collected blood is transferred to a glass slide and stained with a special dye, after which it is examined under a microscope. The number of red blood cells is determined ( and other blood cells), their shape, size, color.

Another option is to place the test material in a special device - a hematology analyzer, which automatically performs a quantitative count of all cellular elements of the blood. This method more accurately determines the number of blood cells, but does not provide information about their shape and structure.

Changes in complete blood count in thalassemia

Blood chemistry

24 hours before blood collection it is necessary to exclude:

• severe physical activity;
• eating large amounts of fatty foods;
• taking certain medications ( if possible);
• consumption of alcohol and/or drugs;

Before starting the procedure, the patient's arm is bandaged with a rubber band in the shoulder area ( the outflow of blood is disrupted, the veins of the arm become filled with blood and become more visible, which makes it easier to determine their location).

Having previously treated the site of the intended injection with a cotton swab soaked in alcohol, the nurse inserts a needle into the vein, to which an empty syringe is attached. The needle should be inserted towards the patient's body, which corresponds to the direction of blood flow in the vein ( this prevents blood clots from forming after the procedure).

While inserting a needle into a vein, the nurse constantly pulls back the syringe plunger. When the needle is in the vein ( as evidenced by the appearance of dark cherry-colored blood in the syringe), the tourniquet is removed from the patient’s shoulder and a few milliliters of blood are drawn into the syringe, after which a cotton ball with alcohol is pressed to the injection site and the needle is removed. The blood is transferred into a test tube and sent to the laboratory for analysis. The patient is asked to sit in the corridor for 15–20 minutes to avoid complications ( dizziness, loss of consciousness).

Biochemical parameters determined for thalassemia

Additional laboratory tests

The following are used in the diagnosis of thalassemia:

• determination of the total iron-binding capacity of plasma;
• determination of ferritin concentration in blood serum;
• determination of erythropoietin levels.

The total iron-binding capacity of plasma reflects the number of free active transferrin centers in the blood. Blood is taken from a vein in compliance with all the rules described earlier. The essence of the method is quite simple - a predetermined excess amount of free iron is added to a test tube with blood. Some of the iron binds to the free active centers of transferrin, the rest is removed and its amount is determined using special instruments. Based on the data obtained, conclusions are drawn about the life insurance system.

Normal values ​​of TLC are in the range from 45 to 77 µmol/l. With thalassemia, the amount of free iron in the blood is significantly higher than normal. All active centers of transferrin are in a bound state and are practically devoid of the ability to bind iron, as a result of which the TCI decreases.

Determination of serum ferritin concentration
Research in recent years has established that the amount of ferritin in plasma is directly dependent on the amount of free iron in the body - as it increases, the concentration of ferritin also increases.

Based on the described mechanism, many methods have been developed for determining the concentration of this protein in the blood. One of the most commonly used is radioimmunoassay. Blood for this study is taken from a vein, in the morning, on an empty stomach ( fence rules are described above).

The essence of the method is as follows - a special substance is fixed on a certain solid carrier ( antibody), which can selectively bind to ferritin. A sample of the blood being tested is added to it, and all the ferritin binds to this substance, forming a strong connection.

The next step is to add other specific antibodies to the solution, to which a radioactive label is attached ( the iodine atom is more commonly used). Free antibodies bind to ferritin and, when the solution is removed, are retained on the solid support.

The last step is a study in a special gamma counter, which allows you to determine the amount of radioactive iodine on the antibodies attached to ferritin. Based on the data obtained, conclusions are drawn about the concentration of ferritin in the blood.

The serum ferritin level depends on gender and is:

• in men – 20 – 250 mcg/l;
• in women – 10 – 125 mcg/l.

Determination of erythropoietin levels
The essence of the method is to determine the amount of erythropoietin in the blood plasma. Radioimmunoassay can also be used for this purpose. The technique and rules of implementation are the same, only instead of antibodies to ferritin, specific antibodies to erythropoietin are used.

The normal concentration of erythropoietin in the blood is 10 – 30 mIU/ml ( international milliunits in 1 milliliter). In thalassemia, this indicator is increased several times, which is due to excess production of erythropoietin by the kidneys.

X-ray examination

Different organs and tissues absorb X-rays at different intensities, causing their shadow images to appear more or less clear on X-ray film. Bone tissue has the maximum absorption capacity in the human body, which is characterized by the lightest areas on x-rays. Air practically does not absorb X-rays and is defined as the darkest area in the image.

X-ray examination of patients with thalassemia can reveal:

• Deformation of the skull bones. Their expansion and decrease in density on the radiograph are noted, which is due to the proliferation of bone marrow and a decrease in the amount of bone tissue.
• Deformation of long tubular bones. It manifests itself as a decrease in bone density, thickening and curvature.
• Increased size of the spleen and liver.

Contraindications to performing an x-ray examination are:

• early childhood;
• tumor processes in the body;
• the presence of metal implants in the area under study.

Ultrasonography

The method is based on the ability of ultrasonic waves ( whose frequency exceeds 20,000 hertz) pass through body tissues and are partially reflected by them. The maximum degree of ultrasound reflection is determined at the boundary of two different media ( e.g. air and liquid, air and organ tissue, organ tissue and bone). In this way, it is possible to obtain an image of internal tissues and organs, to study their structure, density and consistency.

Modern ultrasound machines are quite compact and easy to use, so the examination can be carried out directly in the doctor’s office. The patient lies down on the couch and exposes the part of the body being examined. A special gel is applied to the surface of the skin, which fills microcracks in the skin ( the air they contain may interfere with testing), after which a sensor emitting ultrasound is applied to the skin.

The reflected ultrasound waves are recorded by a special receiver, and after computer processing, an image of the organ or area being examined appears on the screen.

When diagnosing thalassemia, the following is carried out:

• Ultrasound of the liver. The liver is enlarged in size, increased density, heterogeneous consistency, with uneven edges. There may be denser areas consistent with the growth of scar tissue.
• Ultrasound of the spleen. The spleen is significantly enlarged, has a heterogeneous consistency and increased density, and is filled with blood.
• Ultrasound of the kidneys and bladder. Allows you to detect the presence of stones formed as a result of increased excretion of uric acid in the urine.

Bone marrow puncture

The collection of material for research is carried out under sterile conditions using sterile instruments. Most often, bone marrow is taken from the sternum, but puncture of other flat bones is also possible ( pelvic bones, vertebrae).

After treating the puncture site with a solution of 70% alcohol, a syringe with a special needle is used to pierce the periosteum and the upper part of the bone. The needle is advanced 1–1.5 cm deep, after which 0.5–1 ml of bone marrow substance is collected. The needle is removed and the puncture site is covered with a sterile bandage. The resulting material is sent to the laboratory, where it is stained with special dyes and examined under a microscope.

When examining bone marrow puncture from patients with thalassemia, a pronounced increase in the number of cells, mainly erythrocyte precursors, is determined. They have a characteristic structure and size ( small light-colored cells with an accumulation of hemoglobin in the center).

Polymerase chain reaction

The principle of the method is the formation of a large number of copies of a certain gene and its subsequent study. The study requires a small amount of biological material containing cells ( blood, saliva, urine, etc.). The material being studied is placed in a test tube, and a set of special enzymes and reagents is added to it, which activate the process of doubling a strictly defined gene on a specific chromosome, and only if this gene is present in the genetic apparatus of the cell.

In other words, in order to obtain copies of the gene encoding, for example, the formation of the globin a-chain, it is necessary that it be present on chromosome 16 and not be deformed. In this case, special substances recognize this gene, attach and copy it, after which the process is repeated many times. If this gene is not on the chromosome ( for a-thalassemia), no reactions occur.

The same principle is used to determine the presence or absence of all genes responsible for the formation of various globin chains. This helps to establish the form of thalassemia and determine the likelihood of transmitting the disease to descendants.

Elimination of complications of thalassemia

Mild forms of thalassemia often do not require treatment. Such patients are recommended to have a preventive general blood test every six months. In more severe forms, treatment should begin as early as possible, since a lack of oxygen in the body can lead to the development of irreversible changes in the internal organs.

The main directions in the treatment of thalassemia are:

• increasing the level of red blood cells and hemoglobin in the blood;
• eliminating excess iron;
• reduction of urate diathesis;
• surgical removal of the spleen;
• bone marrow transplantation.

Increasing the level of red blood cells and hemoglobin in the blood

The only effective way to increase the number of red blood cells and hemoglobin in the blood is donor blood transfusion. The target hemoglobin level is 100 – 120 g/l.

Indications for blood transfusion are:

• confirmed ( laboratory) diagnosis of thalassemia;
• decrease in total hemoglobin below 70 g/l;
• growth retardation;
• deformation of the skull bones;
• identification of foci of extramedullary hematopoiesis.

Possible adverse reactions during blood transfusion are:

• increased body temperature;
• allergic reactions;
• massive destruction of red blood cells ( as a result of transfusion of incompatible blood);
• infection of the recipient ( patient receiving blood transfusion).

Methods to increase the level of red blood cells and hemoglobin

Elimination of excess iron in the body

Drug treatment of excess iron in the body

Reduction of urate diathesis

Drug treatment of urate diathesis

Surgical removal of the spleen

Indications for surgical removal of the spleen for thalassemia are:

• Development of hypersplenism.
• Severe destruction of red blood cells in the spleen, requiring frequent transfusions of red blood cells.
• A significant increase in uric acid and its salts in the blood that is not amenable to drug therapy.
• Severe jaundice caused by the release of large amounts of bilirubin from destroyed red blood cells.

The operation is performed under general anesthesia. The access is most often laparotomic - an incision is made in the abdomen, the vessels of the spleen are first ligated and then cut, and the organ is removed. The incision site is sutured with sterile threads and a sterile bandage is applied, which is changed every day. After surgery, it is recommended to avoid physical activity for at least one month.

Bone marrow transplantation

Carrying out a bone marrow transplant includes many stages, the main ones being:

• Search for a donor. It is the most important and labor-intensive process, since the donor’s bone marrow must closely match the recipient’s bone marrow according to many criteria. It is recommended that the donor and recipient are not closely related, but if there is no other option, a genetic study is carried out before a bone marrow transplant ( PCR), in order to identify minor forms of thalassemia that do not manifest themselves clinically.
• Donor preparation and bone marrow collection. After numerous compatibility tests, the donor is hospitalized. In a sterile operating room, under general anesthesia, a special needle connected to a syringe is used to puncture the pelvis and femur bones, from which a certain amount of bone marrow is collected. The total volume of material obtained should not exceed 2000 ml. The donor can be discharged from the hospital the next day.
• Recipient preparation. In order for donor bone marrow to engraft, it is necessary first to completely destroy your own bone marrow. For this purpose, for several days before the transplant, the recipient receives maximum doses of potent cytostatic drugs ( busulfan, cyclophosphamide), which ideally should lead to the death of absolutely all hematopoietic cells in the body ( including extramedullary foci of hematopoiesis in the spleen and liver). Sometimes radiation exposure of the recipient's body can be used for the same purpose.
• Injection of bone marrow into the recipient. Bone marrow is administered through a catheter - a special tube installed in the recipient's central vein ( more often subclavian). The process itself is quite simple and is not much different from a regular blood transfusion.
• Monitoring the recipient. For the first 3–4 weeks, the patient requires constant transfusions of all blood components and large doses of antibiotics, since previous chemotherapy has destroyed almost all the body’s protective functions. If the bone marrow takes root, then after a few months the level of hemoglobin and all cellular elements in the patient’s blood will begin to increase. When laboratory data normalizes, the patient is discharged from the hospital ( on average 6 – 8 weeks after transplantation). During the first year, monthly monitoring of blood counts is required, and then a general blood test is performed every six months.

Thalassemia occurs when there is a mutation in the genes that are responsible for the synthesis of peptides - the main elements of hemoglobin. The severity of the disease depends on the number of mutated genes. Thalassemia leads to a deficiency of hemoglobin, a protein that plays a key role in transporting oxygen and carbon dioxide. Hemoglobin molecules contain two alpha globin and beta globin. The gene mutation leads to changes in blood composition and subsequent death of red blood cells.

Thalassemia causes the following effects in the body:

• excess iron occurs in hemoglobin, which disrupts the functioning of the heart, liver and endocrine system;
• Immunity is impaired and the body becomes more susceptible to infections;
• heart diseases develop (arrhythmia and chronic heart failure);
• the volume of bone marrow increases, which leads to deformation of the bones of the skull and limbs;
• the spleen increases in size, where red blood cells mainly die (in severe cases, the enlarged spleen is removed surgically);
• growth and puberty are delayed.

Thalassemia is a hereditary disease, meaning it is passed on to the child from the parents. The risk of developing the disease increases if it has previously been observed in one of your close relatives. Ethnicity is also a risk factor. Thalassemia is most common in the countries of the Mediterranean, Central Asia and Africa.

There are two main types of thalassemia: alpha and beta. The first of them involves a mutation of the genes responsible for the synthesis of alpha globins, and the second - of beta globins. The severity of the disease and its main features will depend on the type of genes affected, as well as on the number of pathological sections of DNA. Considering that alpha globins are encoded by four different genes, the following types of the disease are distinguished:

1. One altered gene is an asymptomatic form. A person is a carrier of the disease and can pass it on by inheritance.
2. Two genes - mild course of the disease.
3. Three genes - severe course of the disease.
4. Four genes is a rare type of thalassemia that is most often fatal. Most fetuses with genetic changes in hemoglobin die before birth, and newborn babies die within the next few days or develop the disease for life. In rare cases, the situation can be saved by a bone marrow transplant from a healthy person with an identical DNA structure and blood composition.

As for beta globins, they are encoded by a single gene located on chromosome 11. If there is a defective gene in only one of the paired chromosomes, a mild degree of the disease develops - thalassemia minor. If both chromosomes are affected, a serious disease occurs - thalassemia major (Cooley's disease).

Symptoms of Thalassemia

Modern medical technologies make it possible to detect thalassemia during prenatal diagnosis. In this case, the expectant mother may be prescribed special treatment that can eliminate the pathology before the birth of the child. In born children, signs of thalassemia appear depending on the type of disease and the number of mutations. In some cases, symptoms are recorded immediately after birth, and in others - during the first two years of life.

The following are common symptoms of the disease:

• pallor or yellowness of the skin;
• growth slowdown;
• darkening of urine;
• deformation of bones, especially the bones of the skull;
• abdominal enlargement.

Diagnosis of thalassemia

Most often, symptoms characteristic of thalassemia do not allow a confident diagnosis. To do this, you need to undergo a special examination. First of all, the patient undergoes a general blood test, which reveals a decrease in the number of red blood cells and the appearance of smaller cells of different sizes and shapes. In addition to mature cells, their precursors, blasts, may be present in the blood.

Other specific blood tests are also prescribed to determine the severity of the disease. Special molecular tests (PCR) may also be prescribed, which help identify mutations at the gene and cellular level. In addition to blood tests, diagnostics of the liver and spleen are required - the organs most affected by thalassemia. In addition, it is necessary to check the condition of the bone tissue. For this purpose, ultrasound and radiography are performed.

It is extremely important to try to diagnose thalassemia in a child during pregnancy, especially if one or both parents have previously had this disease or are potential carriers of it. In this case, diagnostic methods are used such as chorionic villus biopsy (at the 11th week of pregnancy) and amniotic fluid sampling - amniocentesis (prescribed at the 16th week).

Treatment of the disease

When a diagnosis such as thalassemia is made, therapy is prescribed depending on the stage and severity of the disease. If the symptoms are mild or absent altogether, no treatment is carried out. The patient only needs periodic blood transfusions, especially after surgery and childbirth, as well as to prevent various complications. At the same time, people with beta thalassemia require more frequent blood transfusions, and in order to normalize the increased level of iron in the body, they are forced to take specific drugs that bind and remove this substance.

If the disease occurs in a pronounced or severe form, the following treatment methods are used:

1. Frequent blood transfusions (every few weeks), combined with medications that remove excess iron from the body.
2. Bone marrow transplantation is the most effective method of treating thalassemia, allowing you to completely get rid of the disease with a favorable outcome. Transplantation is a serious operation that is not always successful.
3. Taking special medications to correct symptoms and complications.

Prognosis for thalassemia and prevention of complications

The mild form of thalassemia has a fairly good prognosis. These patients do not require ongoing treatment and complications are extremely rare. Moderate and severe forms of the disease also have a favorable prognosis, but for this the patient must undergo regular blood transfusions and use iron-binding drugs.

In most cases, death occurs due to excessive accumulation of iron in the body, as well as disruption of vital organs. However, even negative consequences can be dealt with through surgery. As practice shows, most people who follow the doctor's instructions live a completely normal life.

If a diagnosis such as thalassemia has been made, it is very important to take a responsible approach to starting a family. In case of pregnancy, the expectant mother must undergo a blood test and ultrasound according to a special schedule in order to ensure as early as possible the presence or absence of disease in the fetus. Otherwise, it is recommended to avoid taking any vitamin-mineral complexes or dietary supplements that contain iron. Patients are also prescribed a balanced and varied diet. Finally, they are obliged to carry out timely prevention of infectious diseases through vaccination.