Major thalassemia. Genetic diseases

Thalassemia is a pathology of the blood, which is characterized by disturbances in the formation of one or several hemoglobin chains in red blood cells. This causes the development of small, low-quality red blood cells.

With this disease, there is a deterioration in the transport of oxygen to the tissues and cellular elements of the body. This causes their hypoxia, the manifestations of signs of the disease become apparent.

Previously, the disease was more often observed in climatically hot places where people suffer from malaria: Southeast Asia, Africa, and the Mediterranean countries. But in the modern world, it is diagnosed in a variety of regions due to population migration. Pathology is formed equally in females and males.

About 200,000 children are born with this disease every year, 50% of them are diagnosed with a homozygous form of β-thalassemia. The latter quickly leads to death.

In the heterozygous form, the disease does not manifest itself, this is possible only in extreme situations. However, the risk of its development in descendants is high, they can get it as a hereditary pathology.

Causes of thalassemia

They are well studied, since the disease is quite common. It is reliably known that the first changes are observed in violation of the synthesis of protein chains of hemoglobin, which is able to bind to oxygen molecules and transport them to all tissues of the body.

Most often, the disease develops due to the genes that children inherit from their parents. In those of them that are responsible for the synthesis of hemoglobin, a mutation is detected.

When studying the structure, a pigment is detected, which includes iron and 2 pairs of protein compounds: alpha and beta chains. If the synthesis of one of them is disturbed, then the second one accumulates.

Provoke such changes those genes that are responsible for the formation of hemoglobin protein. With such a mutation, there is a violation of the correct set of amino acids in the chain. The phenomenon is also characteristic of the causative agent of malaria.

Heredity in a child can manifest itself in two ways:

1. Homozygous type of pathology - from mom and dad at the same time.
2. Heterozygous - from one of the parents.

Classification

If the abnormal hemoglobin protein is inherited from both parental sides, then this is a severe form, which is characterized by pronounced manifestations. This is thalassemia major, or Cooley's disease (after the doctor who described it).

It is inherited as a recessive type (two-halle system), based on a decrease in the synthesis of polypeptide chains. If this comes from one parent, then in the absence of extremely unfavorable circumstances, there are no signs.

In the modern classification, the following forms of the disease are distinguished:

• Alpha thalassemia. It is observed in the absence of one or more genes, which normally should be two from the mother and father. It is this amount that ensures sufficient production of alpha-globin chain proteins. In the absence of two genes, symptoms of anemia may appear. With a lack of three genes, hemoglobinopathy H is diagnosed, which is clearly manifested by symptoms of anemia. The absence of four genes is a rather rare phenomenon, which is called “fetal dropsy”. Such children die before, during or immediately after birth..
• Beta thalassemia is observed when one or two genes are disturbed, which normally comes one from father and mother. An insufficient amount of beta-globin protein is produced. With the modification of one gene, a person is a carrier of the disease, the manifestation of moderate anemia is not excluded. When both genes are changed, intermedia beta-thalassemia (Cooley's anemia) is diagnosed at the same time. With the main one, a severe form of anemic syndrome also develops. The homozygous beta form reveals itself by the year of the child's life and differs in the manifestation of signs. Heterozygous (thalassemia minor) is characterized by vague symptoms, or there are no signs at all.

It should be borne in mind that in some cases the homozygous form proceeds easily, it cannot be qualified as thalassemia major, therefore it is noted as intermediate.

This pathology has three degrees:

1. Heavy. Abnormal changes are so strong that the child dies in the first year of life.
2. Medium. A child can live for about eight years.
3. Light form. An adult person dies before reaching old age.

Despite a common diagnosis, β-thalassemia in humans can vary significantly in study results, presentation of symptoms, clinical course, treatment, and future prognosis.

Symptoms and manifestations

Signs depend on the form and time of occurrence of the mutation. Thalassemia major occurs with a homozygous origin, manifests itself in children immediately after birth:

• Elongated cranium.
• The upper jaw is more developed than the lower.
• The facial skeleton of the skull resembles a Mongoloid one.

By the age of one year, the following signs are observed:

• Expansion of the nasal septum, its flattened shape.
• Formation of abnormal bone growths in the feet.
• Eating disorders.
• Yellowness of the skin due to dysfunction of the spleen.

Oxygen deficiency in the tissues causes the following symptoms:

• Liver enlargement, development of early cirrhosis.
• Formation of heart failure. Excess iron accumulates on the myocardial muscle and disrupts the contractile activity of the heart muscle.
• Delay in physiological and intellectual development.
• Formation of diabetes.

Adults show the following symptoms:

• The formation of ulcers on the skin, they are provoked by abnormal disorders in the blood circulation.
• Frequent pneumonia.
• Regular bone fractures.
• Inflammatory processes in the gallbladder associated with the deposition of stones.
• Cardiosclerosis is a pathology of the heart characterized by the growth of a connective scar in the myocardium, muscle replacement and deformation of the valves.
• The formation of sepsis in infectious pathologies.
• Gender disorders.

With the development of an intermediate form of the disease, there are no changes in the appearance of a person, mental and physical development is normal, but there is an increase in the spleen and bone fragility.

Signs of thalassemia major

Observed immediately after birth:

• Elongated skull.
• Mongoloid type of face.
• Enlargement of the upper jaw.
• Enlargement of the nasal septum.

Carrying out a blood test indicates hepatomegaly, which ends with the formation of cirrhosis and diabetes.

If thalassemia is diagnosed at birth, and the signs are bright, then most often such children can live for about a year.

Symptoms of thalassemia minor

If a gene mutation is transmitted from one of the parents, then thalassemia minor develops. Symptoms in this case are blurred or do not appear at all. The clinical picture is as follows:

• Increased fatigue.
• Deterioration in performance.
• Regular headaches, causeless dizziness.
• Pale skin with jaundice.
• Enlargement of the spleen.

The greatest danger of this condition is to increase the risk of infection in the body.

Diagnosis of the disease

The survey includes several stages:

• Collection of anamnesis. Dangerous pathologies that were diagnosed in a woman during pregnancy and could cause the development of pathology are determined.
• Assessment of the course of the childbearing period.
• Thorough examination by a doctor: the general condition of the patient, the condition and color of the skin are assessed, the abdominal region is palpated to determine hepatosplenomegaly.
• Questioning the parents or the patient himself to ascertain the severity of symptoms and the severity of the disease.

The following laboratory tests are also scheduled:

• Blood chemistry.
• PCR tests.
• Study of the biological synthesis of hemoglobin chains.
• General blood test.
• Hemoglobin electrophoresis.

It is also necessary to carry out instrumental diagnostic methods:

• Ultrasound of the abdominal cavity (detects an enlarged spleen).
• X-ray of bones.
• Puncture of the bone marrow.
• The development of the fetus in the womb.

If a homozygous form of pathology is detected, an artificial termination of pregnancy is prescribed.

Treatment

Having determined what it is and what are the signs, it is necessary to choose methods of therapy. Therapeutic measures are primarily aimed at normalizing the amount of hemoglobin.

In addition, there are other methods of treatment:

• In severe forms of the disease, frequent blood transfusions are necessary, but this gives a temporary result.
• Iron chelate is prescribed.
• In modern medicine, it is possible to transfuse thawed or filtered erythrocytes. This procedure is safer for children.
• With an enlarged spleen, its removal is prescribed. Surgical treatment is possible only after 5 years of life, it is necessary to take into account the increased risk of infection.
• Bone marrow transplantation, but finding a donor is problematic.

Clinical recommendations include a special diet, which involves the intake of nuts, tea, soy, cocoa (foods that resist the absorption of iron). Reception of ascorbic acid, which contributes to the removal of iron from the body.

Possible Complications

In moderate and severe forms, therapeutic measures are aimed at prolonging the period of life and eliminating possible complications, such as:

• Pathology of the heart and liver. High levels of iron in the body can cause damage to various tissues, with the heart muscle and liver being the most affected. This often causes death, so regular blood transfusions are necessary.
• The penetration of infection into the body is also often the cause of death of the patient, especially for those who underwent surgery to remove the spleen.
• Osteoporosis. With this pathology, the bone elements are subject to frequent fractures.

Prevention

It is impossible to cure thalassemia, therefore it is necessary to take preventive measures, which are as follows:

• Diagnosis during pregnancy, especially if both parents have thalassemia.
• Conducting genetic research.
• If necessary, an artificial termination of pregnancy is performed.

Forecasts

When diagnosing thalassemia minor, the prognosis is good, the person leads a normal life, the duration of which is almost the same as that of a healthy person.

With beta thalassemia, only some patients are able to survive to puberty.

The severe homozygous form requires ongoing treatment, as only interventions such as blood transfusions keep the patient alive.

Reading 7 min. Views 74

Thalassemia is a disease due to which there is a violation of the synthesis of hemoglobin. The name of the pathology literally means "anemia of the sea coast." The disease is inherited by a recessive type, manifested as a result of genetic mutations. Knowing what thalassemia is will be helpful in family planning.

Classification

For some time, scientists could not figure out what thalassemia is. Only with the discovery of DNA and the properties of polypeptide chains, it was possible to determine the following classification of pathology:

• Alpha thalassemia. At the same time, the synthesis of α-chains of hemoglobin A is suppressed in the body. The disease develops as a result of heterozygous carriage of the manifest, or “silent”, thalassemia gene or homozygous dropsy of the embryo. Sometimes hemoglobinopathy develops H.
• Beta thalassemia. The mechanism of formation of β-chains of hemoglobin A is suppressed in the body. Includes Cooley's anemia, homo- and heterozygous δβ-thalassemia.
• Gamma thalassemia. There is a suppression of γ-chains of hemoglobin.
• Delta thalassemia. There is an inhibition of δ-chains of hemoglobin.
• Thalassemia, due to which the structure of the blood protein responsible for the transfer of oxygen is disturbed.
• Lepore-hemoglobinopathies.
• Hemoglobinopathy Constant Spring (GS).

The most common is beta thalassemia. It can be small, large and intermediate. A small form of the disease is characterized by a slight severity of symptoms. According to the severity of the course, the pathology is divided:

• on the lung (patients can survive until the onset of puberty);
• for moderate (life expectancy of patients does not exceed 10 years);
• to severe (death occurs in the first years of life).

Gamma and delta variants of the disease are extremely rare.

How often do you take a blood test?

Poll Options are limited because JavaScript is disabled in your browser.

Only by appointment of the attending physician 30%, 950 votes

Once a year and I think it's enough 18%, 554 vote

At least twice a year 15%, 460 votes

More than twice a year but less than six times 11%, 344 vote

I monitor my health and take it once a month 6%, 197 votes

I'm afraid of this procedure and try not to pass 4%, 135 votes

21.10.2019

The reasons

Thalassemia is a genetically determined pathology that is inherited in an autosomal recessive manner. The immediate causes of the development of the disease are mutations in the gene that codes for the synthesis of a particular chain of hemoglobin. The mutation occurs as a result of abnormal RNA synthesis, inefficient gene transcription. Due to mutations, the synthesis of hemoglobin protein polypeptide chains is disrupted, due to which it loses its functions.

An excess or deficiency of some hemoglobin polypeptide chains leads to a disruption in the formation of erythrocytes, to their gradual destruction. In beta thalassemia, "fetal" hemoglobin accumulates in red blood cells. It cannot carry oxygen to tissues and cells, which is why they experience oxygen starvation.

Due to the growth of the bone marrow, a violation of the structure of the skeleton occurs. As a result of oxygen starvation, anemia and inefficient formation of red blood cells, the normal development of the child is delayed.

The homozygous form of thalassemia has 2 pathological genes that are inherited from two parents. In heterozygous thalassemia, a person has only 1 gene inherited from one parent.

Symptoms

If a child was born with thalassemia, its symptoms appear from the first weeks and months of life. The general clinical picture of the disease includes the following signs:

• change in the shape of the skull (it has an almost square shape);
• saddle shape of the bridge of the nose;
• the presence of a Mongoloid incision of the eyes (i.e., the palpebral fissure narrows in a child);
• increase in the upper jaw;
• enlargement of the liver, spleen (these processes develop from the first days of the patient's life);
• hemosiderosis (accumulation in the tissues of hemosiderin pigment, which is formed due to the breakdown of hemoglobin);
• pallor and yellowness of the skin and mucous membranes;
• deposition of bilirubin stones in the bile ducts;
• dropsy of the fetus (this symptom is incompatible with life, because the disease irreversibly affects the brain);
• lag in sexual and physical development;
• malocclusion;
• weakness;
• fatigue;
• decreased immune defense.

Currently, there are a huge number of hereditary diseases that a child receives along with genes from mom or dad. For some to manifest, it is necessary that both parents pass on the defective gene to their baby. One such disease is thalassemia. Few people know what kind of disease it is. In our article, we will try to deal with this.

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, it is said that there is a homozygous thalassemia. The disease is characterized by the fact that the production of hemoglobin is disrupted, and it plays a major role in the transport of oxygen throughout the body.

Hemoglobin is a protein, which in its composition 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 the alpha thalassemia and beta thalassemia.

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

Disease classification

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

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

In each case, the severity of symptoms can vary significantly. Given this, 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. It is inherited from only one of the parents.

All varieties are characterized by their symptoms and severity of the course.

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 parent's autosome. This means that the probability of getting sick is 100% for someone who received defective genes for this trait from mom and dad.

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, in Africa. Some associate thalassemia with malaria, as outbreaks of the disease are common in these regions.

The blame is attributed to the fact that a mutation occurs in the genes and thalassemia develops, the photo shows that a large number of patients are also 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 affect 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 inheriting pathology from only one of the parents, we can talk about small or heterozygous thalassemia. Since there is a second healthy gene in the genotype, it significantly smoothes the manifestation of the disease, and the 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 is greatly increased.

Diagnosis of the disease

Medicine has the ability to diagnose thalassemia in the early stages of development, diagnosis is based on laboratory blood tests. They immediately show that hemoglobin has a disturbed structure. You can even determine in which of the chains there are deviations.

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

It is possible to make a diagnosis of thalassemia already in the early stages of pregnancy, take the amniotic fluid for analysis and examine it. It will always contain fetal erythrocytes, the study of which can establish the presence of pathology.

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

beta thalassemia

If a beta type 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 is 97% of the total number of molecules. If you understand, 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 work of the genes responsible for the synthesis of chains. At present, it has already 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 manifestation of these mutations. As a result, it turns out that in people with the same mutations in the genes responsible for the synthesis of hemoglobin, the degree of manifestation of the disease can vary greatly.

Varieties of beta thalassemia

The clinical picture of the disease may be different, depending on this, beta-thalassemia is divided into several groups. Not everyone is familiar with such a concept as thalassemia, that this disease depends on many genetic factors, and not everyone is also aware.

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

1. normal gene. It is in this state that it is found in all healthy people.
2. Virtually destroyed by mutation gene. The beta chain is not synthesized at all.
3. A partially damaged gene can only partially do its job, so the synthesis of chains goes on, but in insufficient quantities.

Given all this, the following types of thalassemia are distinguished:

Alpha thalassemia

In hemoglobin, in addition to beta, there are also alpha chains. If their synthesis is disturbed, then we can talk about such a form as alpha thalassemia. The disease is manifested by the formation of only a beta chain, and this is fraught with the fact that hemoglobin of such a 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 child receives from the mother, and the second from the father.

Varieties of alpha thalassemia

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

If alpha-thalassemia is mild, treatment may not be needed, 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.

Thalassemia treatment

We figured out thalassemia - what kind of disease is it. Now it is necessary to stop on treatment. It can be noted that therapy is aimed at maintaining hemoglobin at the required level and eliminating the heavy load of the body from a large amount of iron. Also, the methods of treatment include the following activities:

In addition to the above methods of treatment, symptomatic therapy is also carried out, which alleviates the patient's condition.

Disease prevention

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

1. Carrying out prenatal diagnosis.
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 with such a diagnosis in your family, then it is advisable to visit a geneticist before planning a pregnancy.

In every organism there is a huge number of mutating genes, it is practically impossible to predict where and when a mutation will manifest itself. For this, genetic consultations exist to help couples understand their pedigree, or rather, diseases that are transmitted from one generation to another.

Prognosis for patients with thalassemia

Depending on the severity and form of the disease, the prognosis may be different. With thalassemia minor, patients live a normal life, and its duration practically does not differ 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 do regular blood transfusions. Without this procedure, the life of the patient is almost impossible.

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

• What is Thalassemia
• Symptoms of Thalassemia
• Thalassemia Treatment
• Which Doctors Should You See If You Have Thalassemia

What is Thalassemia

Under thalassemia understand a group of hereditary diseases manifested by a violation of the synthesis of any of the globin chains. With this form of pathology, hypochromic anemia is noted with a normal or elevated serum iron content.

The disease in question was first described by American pediatricians in 1925. They observed 5 children from families of Italian emigrants. The children showed signs of severe hypochromic anemia, a significant enlargement of the liver and spleen, and bone changes. After the publication of the message, the work of Italian authors appeared, describing a similar, but much milder form of the course of thalassemia, in which persons suffering from this pathology lived to adulthood.

Term "thalassemia" was proposed in 1936. Cooley's disease became known as thalassemia major ( thalassemia major), considering it as a homozygous form of hereditary pathology. For the first time, the idea that thalassemia is the result of a violation of the synthesis of globin chains was independently expressed by several scientists. Thalassemia, in which the synthesis of the globin beta chain is disrupted, is called beta thalassemia; in α-thalassemia, the synthesis of the α-chain is disrupted. Cases of y-, S-, 8-thalassemia with impaired synthesis of the corresponding globin chains are also described. The most common is beta thalassemia.

Pathogenesis (what happens?) during Thalassemia

In thalassemia, one of the globin chains is synthesized in small amounts or not at all. Normally, the synthesis of globin chains is balanced. The number of a- and non-a-chains is the same, and there are no free globin chains in the norm. Disturbed synthesis of one of them leads to imbalance. The chain, which is produced in excess, aggregates and is deposited in erythrokaryocytes. Most of the clinical manifestations of thalassemia are associated with this.

With α-thalassemia, in most cases, there is a loss of a portion of the chromosome of the structural genes responsible for the synthesis of the α-chain, it is encoded not by one, but in most people by two pairs of genes located on chromosome 11. The absence of the α-chain in the fetus leads to the development of dropsy and intrauterine death. A deletion in one of the 4 α-chain encoding genes causes a mild α-chain deficiency; a deletion in 2 genes is a more pronounced deficiency, but the clinical manifestations of the disease largely depend on which 2 genes do not function - on the same chromosome or on different ones. The value of 2 pairs of genes responsible for the synthesis of the a-chain is not the same: one pair is the main one, the other is secondary. The clinical picture also depends on in which 2 of the 4 genes the mutation occurred. If 3 genes are missing, then patients have hemoglobinopathy H. Hemoglobin H consists of 4 beta chains. It is very unstable, aggregates, and at the same time, severe hemolytic anemia develops.

The mechanism of beta-thalassemia is much more complicated. The synthesis of the beta chain is impaired in a number of different diseases: beta thalassemia, hereditary persistence of fetal hemoglobin, hemoglobinopathies Lepore. However, these disorders are not the same. The gene encoding the synthesis of the beta chain is located on chromosome 16. On the same chromosome next to it are the genes responsible for the synthesis of the y- and 8-chains. In beta thalassemia, when the beta chain is not produced at all, gene deletions could not be detected. In thalassemia, there are signs of RNA instability. The main cause of some cases of beta thalassemia is a violation of splicing (the process of "stitching" the coding regions). Splicing refers to the changes that mRNA undergoes on its way from the nucleus, where it is synthesized, to the cytoplasm. Primary mRNA transcripts are arranged in such a way that protein-coding regions alternate with non-coding regions. These non-coding regions are normally excised from the RNA molecule, and the coding parts of the molecule are connected to each other. Disruption of splicing can lead to disruption of mRNA stability.

The deletion of the gene responsible for the synthesis of the 8-chain was also found in other forms of pathology. This is beta-8-thalassemia. The deletion of the 0- and 8-chain gene was found in hereditary persistence of fetal hemoglobin. This is a peculiar disease with very mild anemia or without it, when the content of fetal hemoglobin is greatly increased (up to 95-98%). In contrast to homozygous beta-thalassemia, in which the same high fetal hemoglobin content is sometimes found, with hereditary persistence of fetal hemoglobin, there is no imbalance in the synthesis of chains. Hemoglobinopathies Lepore - a consequence of a deletion in the genes responsible for the synthesis of 8- and y-chains.

Symptoms of Thalassemia

At the heart of the clinical manifestations of thalassemia, the main importance is attached to an excess amount of the globin chain. So, in beta-thalassemia, due to a violation of the synthesis of the beta chain, there are many free a-chains. Excessive synthesis of the a-chain is the main cause of inefficient hematopoiesis in beta-thalassemia. Erythrocytes die in the bone marrow. The death of erythrocytes and, to a lesser extent, reticulocytes and erythrocytes of peripheral blood in the spleen leads to severe anemia. In this case, foci of red hematopoiesis can form in the spleen and liver. Intensive hematopoiesis in the bones can lead to their distortion, severe hypoxia - to a violation of the development of the child. There is a correlation between the depth of anemia and excess of the a-chain in beta-thalassemia. With a higher content of fetal hemoglobin, cells are destroyed less. This is due to the fact that excess a-chains are not in a free state, but in a state associated with y-chains in the form of hemoglobin F. Some patients with homozygous thalassemia do not have severe signs of the disease. Their anemia is not so deep, they can live without constant blood transfusions, and clinically the disease is not defined as thalassemia major, but as thalassemia intermedia. There are patients with more severe heterozygous beta-thalassemia. In these patients, inclusions of precipitated excess a-chains are often found. The severity of heterozygous thalassemia in these patients is due to the insufficient ability of cells to get rid of excess a-chains. Usually, in heterozygous thalassemia, there is a compensatory increase in the utilization of excess a-chains.

With α-thalassemia, in the absence of synthesis of the α-chain and, in connection with this, hemoglobins A, A2 and F, dropsy of the fetus develops, which leads to its death. An excess of beta chains in thalassemia is able to form hemoglobin, consisting of 4 beta chains - hemoglobin H. Cells containing hemoglobin H are very easily removed from the circulation by the spleen. Anemia in hemoglobinopathy H is due to both hemolysis of peripheral erythrocytes and impaired synthesis of globin.

homozygous beta -thalassemia

In homozygous beta-thalassemia, which was described in 1925, clinical manifestations are noted by the end of the first or, less often, the second year of a child's life. In the first months of life, only moderate anemia is found, and it is far from always clear whether the child inherited the disease from one or both parents.

homozygous beta-thalassemia is accompanied by a significant increase in the spleen, jaundice and a grayish tint of the skin and mucous membranes, severe pallor. A sharp hyperplasia of the hematopoietic bone marrow leads to a wide variety of skeletal deformities: an almost square skull, a strongly flattened bridge of the nose, narrowing of the palpebral fissures are noted.

X-ray examination reveals an increase in the thickness of the spongy layer of the bones of the cranial vault, as well as transverse striation on the outer plate of the frontal and parietal bones. Children lag behind in physical development, their resistance to various infections is reduced, sexual development is delayed and even disturbed.

The content of hemoglobin is reduced to 30-50 g/l. Developed hypochromia of erythrocytes is revealed, the color index is usually 0.5 and lower. The number of reticulocytes is increased, the irritation of the red germ is much more pronounced than the reticulocytosis corresponding to this irritation. The content of reticulocytes rises to 2.5-4%. Serum iron content is most often elevated, but may not go beyond the upper limit of normal. In the bone marrow, the content of sideroblasts is increased.

An increase in the level of bilirubin due to the indirect fraction is a characteristic feature of the homozygous beta-thalassemia.

Due to excessive deposition of iron, cirrhosis of the liver, cardiosclerosis, and diabetes mellitus are formed. There is also an underdevelopment of secondary sexual characteristics.

According to the severity, they distinguish: severe homozygous thalassemia, in which patients die in the first year of life, moderate, in which children live up to 5-8 years, and a milder form, which allows patients to live to adulthood.

Diagnosis of homozygous beta-thalassemia is confirmed by the study of the content of fetal hemoglobin in erythrocytes. With homozygous thalassemia, this indicator increases to 20-30.

Heterozygous beta thalassemia

Heterozygous beta- thalassemia - the result of inheritance of the disease from only one of the parents, possibly with an asymptomatic course or with mild clinical manifestations. Violent clinical manifestations are the most rare. Complaints of patients with heterozygous thalassemia are of a general nature and are manifested by weakness, increased fatigue, decreased performance, the most seriously ill patient perceives physical labor. The skin of such patients is pale, a slight icterus of the skin and sclera is characteristic.

An enlarged spleen is a fairly common symptom of heterozygous beta-thalassemia.

Blood parameters in heterozygous thalassemia are extremely diverse. The hemoglobin content may be close to normal. So-called thalassemia minima accompanied by hemoglobin values ​​of 110-120 g/l, or it is reduced to 90-100 g/l ( thalassemia minor), rarely the indicator reaches 70 g / l. Anemia is hypochromic. The decrease in color index can be significant (0.5-0.7). In addition to erythrocyte hypochromia, anisocytosis and poikilocytosis, erythrocyte targeting are often detected.

Also, erythrocyte targeting is found in iron deficiency anemia, lead intoxication, in individuals who have undergone splenectomy.

A typical sign of thalassemia is basophilic punctured erythrocytes.

The content of reticulocytes in heterozygous thalassemia usually rises to 2-5%. A significant irritation of the red germ of the bone marrow is found. Often the red sprout is 1-3 times higher than the white one. The number of mature erythrokaryocytes containing hemoglobin is reduced. The content of iron granules in the bone marrow is increased or, rarely, normal. Serum iron content in patients with heterozygous thalassemia is normal, rarely elevated. Iron reserves, determined by the desferal test, are elevated.

In 75% of cases of heterozygous beta-thalassemia, an increase in the level of indirect bilirubin is detected.

The diagnosis of heterozygous beta-thalassemia is made on the basis of an increase in the content of the hemoglobin A2 fraction. The content of hemoglobin A2 in heterozygous beta-thalassemia increases to 4.2-8.9% of the total amount of hemoglobin. Approximately half of the patients show an increase in the content of fetal hemoglobin up to 2.5-7%.

An important diagnostic feature is a similar disease in family members of the patient.

Alpha thalassemia

The synthesis of the α-chain of globin, in contrast to the synthesis of the beta-chain, is controlled by two pairs of genes that are not the same in value; therefore, there are various variants of the course of α-thalassemia.

In the complete absence of the a-chain, homozygous dysfunction of all 4 genes, fetal hemoglobin is not synthesized in the fetus, dropsy develops, resulting in death. Violation of the function of 1 or 2 genes leads to anemia, usually mild. Clinical manifestations of a-thalassemia with damage to 2 genes depend on which genes are affected, and almost completely repeat heterozygous beta-thalassemia. Often there is an enlargement of the spleen, less often - the liver.

Moderate hypochromic anemia with target erythrocytes and erythrocytes with basophilic puncture, a slight increase in the level of reticulocytes, a slight hyperbilirubinemia and an increase in serum iron, an increase in the osmotic resistance of erythrocytes are determined. There is a sharp irritation of the red germ of the bone marrow. As a rule, blood relatives of the patient have the same anemia.

However, unlike beta-thalassemia, α-thalassemia does not increase the amount of fetal hemoglobin and hemoglobin A2. α-thalassemia can be diagnosed only in the case of studying the biosynthesis of globin chains in vitro (in vitro).

Alpha thalassemia is sometimes detected in newborns: a blood test detects hemoglobin Bart, devoid of an a-chain. This hemoglobin consists of 4 y-chains.

Hemoglobinopathy H is one of the variants of α-thalassemia. It is relatively mild, manifested by an increase in the size of both the spleen and liver, slight jaundice, mainly due to an increase in the fraction of indirect bilirubin, anemia of varying severity, usually the hemoglobin content does not fall below 70-80 g / l. Marked hypochromia of erythrocytes, their targeting, basophilic puncture are noted. As with other forms of thalassemia, with hemoglobinopathy H, signs of ineffective hematopoiesis are found: a sharp irritation of the red germ of the bone marrow with a slight increase in the level of reticulocytes. Hemoglobinopathy H differs from other forms of thalassemia by multiple small inclusions in all erythrocytes.

Hemoglobinopathy H was first described in 1955 by Rigas et al. These scientists observed 2 patients with hemolytic anemia, in whom an additional fraction moving ahead of hemoglobin A was detected during hemoglobin electrophoresis in alkaline buffer.

Hemoglobinopathies Lepore - these are forms of thalassemia in which the synthesis of the a-chain of globin is normal, and the synthesis of the second chain is impaired. Instead of a normal beta chain, a peculiar chain is synthesized, consisting of fragments of 0- and 8-chains. Clinical signs of hemoglobinopathies Lepore very similar to those in homozygous beta thalassemia.

About 70-80% of fetal hemoglobin and about 20% of hemoglobin are detected Lepore. Heterozygous form of hemoglobinopathies Lepore clinical and hematological features cannot be distinguished from heterozygous thalassemia. The content of hemoglobin ranges from 90 to 100 g/l, the spleen is often enlarged. Heterozygotes have a hemoglobin content Lepore is 7-8%, while the content of hemoglobin A2 decreases and the content of fetal hemoglobin increases.

Hemoglobinopathies Lepore are rare.

Thalassemia Treatment

Treatment of homozygous thalassemia. Since the manifestations of the disease are determined by hypoxia and active hematopoiesis in the bones, where it is usually absent, erythrocyte transfusions are carried out to the patient from an early age.

Initially, a shock course of treatment is applied (8-10 transfusions in 2-3 weeks). In this case, the hemoglobin content usually rises to 120-140 g/l. Then transfusions are done less frequently, every 3-4 weeks, at the rate of 20 ml/kg. They try to maintain the level of hemoglobin at 90-100 g / l. Massive transfusions for thalassemia not only improve the general condition, but also reduce skeletal changes, enlargement of the spleen, improve the development of children, and reduce the incidence of severe infections.

Frequent complications of this therapy are pyrogenic reactions, mainly with the use of whole blood or insufficiently washed erythrocytes.

One of the serious complications of transfusion is excessive deposition of iron-containing pigment, which leads to a significant increase in the liver, diabetes mellitus, and heart failure. Treatment of homozygous thalassemia includes the obligatory use of Desferal to remove excess iron. The dose of Desferal (administered intramuscularly) depends on the number of transfused erythrocytes and the age of the patient: for young children - 10 mg / kg, for adolescents - 500 mg / day. Large doses are also acceptable - 1 g / day. It is recommended to combine Desferal with 200-500 mg of ascorbic acid orally.

A significant increase in the spleen, the addition of leukopenia, thrombocytopenia to the signs of hypochromic anemia make one think about splenectomy.

Treatment of homozygous thalassemia by these methods improves the general condition of patients, increases their life expectancy.

Currently, bone marrow transplantation is widely used in patients with thalassemia, as a result of which stable improvement is achieved in most cases.

Treatment of heterozygous beta thalassemia not required in most cases. Patients feel well. The content of hemoglobin ranges from 90 to 110 g/l. With heterozygous beta-thalassemia blood transfusions are not required. Removal of the spleen is extremely rare and only with a very large spleen.

Desferal should be used in heterozygous beta-thalassemia when there is a high amount of serum iron and iron in the urine after the administration of 500 mg of desferal. However, Desferal only prevents siderosis (a human disease caused by deposition of dust containing iron in the lungs), without leading to an increase in hemoglobin levels.

With a decrease in the level of hemoglobin due to infectious diseases, during pregnancy it is necessary to use folic acid at 0.005 g 1-2 times a day, since with ineffective hematopoiesis associated with thalassemia, a significant amount of folic acid is consumed.

In heterozygous thalassemia, iron preparations are contraindicated, since there is always some excess of iron without clinical manifestations of hemosiderosis. However, patients taking iron supplements feel much worse. The most dangerous in thalassemia is the parenteral administration of iron preparations: patients who were in a satisfactory condition may die from severe hemosiderosis, in particular from circulatory failure associated with myocardial siderosis.

Treatment of a-thalassemsh practically does not differ from the treatment of heterozygous thalassemia, with the exception of H.

With hemoglobinopathy H, due to the instability of this hemoglobin and its precipitation, there are signs of not only ineffective hematopoiesis, but also a pronounced destruction of peripheral blood erythrocytes. This destruction occurs mainly in the spleen, as a result of which it increases. The main treatment for hemoglobinopathy H in severe anemia is the removal of the spleen.

Violation of the general composition of the components present in the blood can provoke the occurrence of a huge number of diseases, many of which are familiar to patients. However, there are those about which they have no idea. In this article, we will pay attention to one of these ailments, having studied in more detail what kind of thalassemia disease is, what are the methods for diagnosing it and how to further fight the disease.

Thalassemia and its classification

Many parents, faced with such a disease, are wondering what is thalassemia? Thalassemia is a so-called group of diseases that involves a violation of the process of synthesis of hemoglobin chains. In medicine, this disease is considered hereditary, that is, having a predisposition in a child at the genetic level. It should be noted that such a syndrome is a fairly common phenomenon among born babies.

Depending on what the course of the disease is and what its form is, thalassemia can be divided into:

• severe - can only be detected in a child during the first year of life, since it is this period that the child will be able to live with this kind of blood composition disorders;
• fatal - a disease is detected in a child under 8 years of age, in this case the disease proceeds less intensively than in the previous form;
• light - is found at a more conscious age, however, even in this form a person can live for a relatively short time.

In addition, this disease is divided as follows. Allocate:

• homozygous thalassemia - can be acquired from both parents, characterized by an excessive presence of red pigment, while it can occur closer to a year after birth and have a number of fairly pronounced symptoms and disorders in the child's body;
• heterozygous thalassemia - has another name - thalassemia minor, which is the result of the transition of pathology from one of the parents, in this case, signs of anemia are practically not expressed in the child, and symptomatic signs and disorders are completely absent.

The division of this disease described above takes place only in the case of the classical variant of thalassemia. Violations of such a division of thalassemia are not excluded. In any case, the patient needs an urgent consultation with a specialist, further examination and immediate effective treatment of the disease.

Causes

What is thalassemia disease and what are its main causes? The main cause of thalassemia among patients is the manifestation of mutations in the DNA of cells responsible for the level of hemoglobin. As a result, there may be a violation of the process of normal performance of this substance, which ultimately leads to the occurrence of a hemolytic process - anemia or anemia in a child.

As mentioned earlier, the process of transmission of the disease is carried out from parents to children.

In addition, the causes of the disease should include:

• synthesis of abnormal messenger RNA;
• deletion of structural genes;
• mutations of regulatory genes;
• inefficient gene transcription.

All these causes contribute to gradual bone marrow hyperplasia, which entails deformation of the bone tissue of the patient's skeleton. Such violations negatively affect the further development of the child, especially his growth.

Symptomatic signs

All pronounced signs of thalassemia directly depend on the severity of the disease itself and on the age characteristics of the patient. The most common symptoms in a child include:

• constant feeling of fatigue even after a long rest;
• the presence of a feeling of weakness throughout the body (the reason for this is a decrease in hemoglobin levels);
• violation of the correctness of the shape of the facial skeleton;
• difficulty or complete stop of general development (mainly its slow progress);
• the occurrence of flatulence due to excessive accumulation of gases;
• change in the appearance of urine (it becomes dark brown).

Each type of disease such as thalassemia is characterized by its own specific symptoms, which are presented in more detail in the table:

Typical type of disease	The most common symptoms
Alpha thalassemia moyora	change in the appearance of the skin (in most cases become pale); bloating is found; hematological disorders in newborns.
Beta thalassemia minor	hemolytic anemia is diagnosed; increased pallor of the epidermis; detection of hepatosplenomegaly; pronounced changes in bones; malocclusion; changes in blood sugar levels; pathological processes in the thyroid gland; in some cases, paralysis may occur, especially in a child with severe anemia.

As for the functionality of the internal organs, in many patients an increase in the liver and spleen can be detected, which is actively affected by the impaired type of hematopoiesis. The protective function of the child's body decreases, which entails the constant transfer of various infectious and viral diseases from the side of a small patient. The disease thalassemia and the symptoms of its manifestation are individual.

Diagnostic measures

Diagnosis of the disease in patients is carried out by conducting certain studies, the main of which include:

• study of the bone marrow;
• hemoglobin electrophoresis;
• taking a blood test to determine the level of hemoglobin.

In most cases, with thalassemia, it is enough for the patient to take a general blood test, the results of which may already indicate the presence of a pathological process and a violation of the child's health.

A comprehensive examination before the birth of a child should be carried out at 11 weeks of pregnancy. For this, a fragment of the placenta is taken, and the infection of the fetus with thalassemia is determined by examining the amniotic fluid at about 16 weeks.

For this, specialists use a special needle, with this needle they take a sample for further study.

Currently, the latest technology of preimplantation genetic diagnosis of thalassemia is especially popular. This method enables the mother to give birth to a healthy child in the future. Since the main diagnosis is a laboratory study of analyzes, it makes sense to pay attention to the interpretation of the results obtained and to what are the deviations from the norm of the main indicators:

• when studying blood, the level of hemoglobin decreases to common limits - 50-30 g / l;
• a disappointing color indicator as a result of calculations varies between 0.5 and below;
• erythrocytes have changed sizes;
• resistance of blood cells is clearly increased;
• the number of reticulocytes significantly exceeds normal values.

Changed for the worse and bilirubin, which in turn indicates an excessive amount of iron present. Such violations can provoke the occurrence of parallel diseases - cirrhosis of the liver and the development of diabetes mellitus. In some cases, damage to cardiac functionality is not excluded.

Basic Treatments

Thalassemia disease implies a comprehensive treatment that makes it possible to prevent its further progression. In this case, the treatment of thalassemia has its own specific features. The detection of this oxygen deficiency at the cellular level indicates that the patient needs an emergency blood transfusion. At the initial stages of the treatment of the disease, this patient needs about 10 transfusions. This method is essential to restore the level of hemoglobin in the blood to normal levels. Subsequently, the total number of transfusions decreases, but the hemoglobin level is carefully monitored.

This technique for the treatment of thalassemia is aimed at:

• improvement of the general condition of the patient;
• elimination of the possible detrimental effect of the disease on the skeletal system;
• increase and strengthen the immune system;
• preventing further enlargement of the spleen;
• favorable development of the child.

It is especially important for specialists to remove excess iron from the body during treatment. In this case, intramuscular injections of Desferal are prescribed, especially in combination with vitamin C. Often, for a stable improvement in the general state of health, the patient may be shown surgical treatment for bone marrow transplantation.

However, there are difficulties here, for example, with the selection of a donor and the subsequent recovery period after surgical treatment.

The most common and effective treatments for Thalassemia include:

1. Transfusion of erythrocytes. This is especially true when diagnosing a severe form of the disease. Over time, the patient begins to develop the so-called transfusion dependence. This reaction of the body is characterized by a stable decrease in hemoglobin. This may threaten the life of the patient or the disease will begin to actively progress. This procedure has significant drawbacks. In this case, problems may arise with the search for the most suitable donor, since careful individual selection is required.
2. Splenectomy. This procedure is called splenectomy, and the method is considered necessary due to the effect of an enlarged organ on hemoglobin values. Thus, the elimination of this internal organ can affect the course of the disease. The operation can be performed only when reaching the age of 8. However, this also has its drawbacks, since liver enlargement can be provoked. The decision to remove an organ should be made with extreme caution.
3. Bone marrow transplant. It is considered one of the radical methods of therapy. It is important to conduct a biological study of all family members for compatibility. This will make it possible to find a more suitable donor. In addition, this procedure has a relatively high cost.

Not less popular is the elimination of the disease thalassemia and treatment with the help of genetic engineering. In this case, it is important to adhere to a specially selected diet (table number 5), drink drinks that contain tannin, such as tea or cocoa. To maintain the functionality of the liver, the patient can be prescribed medications - hepatoprotectors: lipoic acid, vitamin E, Essentiale, as well as a course of choleretic herbs - mint, barberry and tubage.

There are also ways to treat other forms of thalassemia disease, such as interstitial. In this case, the patient does not need a constant blood transfusion, it can be limited to only single procedures that are carried out in the interval from several weeks to several months.

Summing up all of the above, it should be noted that such a disease as thalassemia can be completely eliminated only in isolated cases, provided that it is diagnosed in the early stages of development. It is important to carry out the necessary treatment in order to prevent possible complications and prolong the life of the patient.

In contact with