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Thalassemia: cause, symptoms, diagnosis

by Josephine Andrews
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Thalassemia, or Mediterranean anemia, is a genetic disease of red blood cells. Due to a defective gene, the body produces too little red blood pigment (hemoglobin) or it is broken down too quickly. Depending on the location of the genetic defect, a distinction is made between alpha and beta thalassemia. Both forms lead to anemia. The doctor usually treats this with medication and blood transfusions. Read more about causes, symptoms, diagnosis and treatment here!

ICD codes for this disease:

ICD codes are internationally valid codes for medical diagnoses. They can be found, for example, in doctor’s letters or on certificates of incapacity for work.

D57 D56

quick overview

  • Description : Genetic disease of the red blood cells (erythrocytes) that leads to anemia.
  • Diagnosis: The doctor diagnoses thalassemia through a special blood test and an analysis of the genetic material (DNA analysis).
  • Causes: An inherited genetic defect that causes the body to produce too little or no red blood pigment ( hemoglobin ).
  • Treatment: The treatment is drug and blood transfusions, in some cases a bone marrow transplant is necessary.
  • Symptoms: Among other things, anemia, fatigue, an enlarged liver and spleen, growth disorders, bone changes, osteoporosis; in mild forms of thalassemia, there are often no symptoms.
  • Prognosis: Thalassemias vary in severity. The sooner symptoms are treated, the better the prognosis. A cure is currently only possible with a stem cell transplant or gene therapy.

What is thalassemia?

Thalassemias (also Mediterranean anemias) are a group of genetic diseases in which the formation of red blood cells (erythrocytes) is disturbed by a genetic defect. As a result, the body produces too little or no red blood pigment (haemoglobin) or it is broken down too quickly.

The blood cells are usually smaller than normal due to the altered hemoglobin and have a shorter lifespan, which over time leads to anemia, accompanied by typical symptoms such as tiredness and an accelerated heartbeat.

Thalassemia is one of the most common blood disorders in children and adolescents. They also belong to the group of hemoglobinopathies (hemoglobin disorders). Thalassemia can be inherited from generation to generation. Since thalassemia is particularly widespread in the Mediterranean region, it is also known as “Mediterranean anemia”.

How does thalassemia develop?

Hemoglobin is a protein that is contained in the red blood cells and is formed in the bone marrow. It enables red blood cells to carry vital oxygen from the lungs to all parts of the body.

Hemoglobin is normally made up of four protein chains, two of which are the same – two alpha and two beta chains. Hemoglobin also contains iron, which binds oxygen. In the case of thalassemia, the body forms no, too few or altered protein chains (alpha or beta chains) due to an altered gene (mutation).

As a result, fewer hemoglobin molecules can form that are functional. The red blood cells become smaller and increasingly break down. As a result, anemia occurs because the body is no longer sufficiently supplied with oxygen due to a lack of red blood cells.

Depending on which protein chain (alpha or beta chain) is affected, a distinction is made between α-(alpha)-thalassemia and β-(beta)-thalassemia.

alpha thalassemia

The rarer form is α-thalassemia. In this form, the body forms too few or no alpha chains at all.

beta thalassemia

Beta thalassemia is the more common form of thalassemia. In this form, the body produces too little or no beta hemoglobin chains.

There is also delta and gamma thalassemia, but both are very rare and usually mild.

How is thalassemia diagnosed?

Since the symptoms of thalassemia often appear in childhood, the first point of contact is usually the pediatrician. If necessary and for further examinations, he or she will refer you to a specialist in internal medicine (haematologist).

family history

Since thalassemia is an inherited disease, family history usually provides the doctor with the first clues. For example, the doctor asks whether there are known carriers of the disease in the family.

blood test

To confirm the diagnosis, the doctor performs a blood test including hemoglobin electrophoresis (Hb electrophoresis).

Hemoglobin Electrophoresis

In hemoglobin electrophoresis, the doctor dissolves hemoglobin from the patient’s blood in a liquid and applies it to a special carrier material (e.g. paper or gelatin). Then he applies a voltage.

Depending on the composition of the hemoglobin, it moves at different distances in a given time. Based on the distance traveled, the doctor assesses whether the hemoglobin is normal or defective.

Under a microscope, the doctor can usually see the characteristically shaped cells in the affected person’s blood. These are relatively pale red blood cells with a darker colored deposit of hemoglobin in the center. The blood cells are small and low in hemoglobin.

diagnosis in babies

Doctors recommend that newborns with a family history of thalassemia have blood tests (eg, newborn screening) done. To do this, the doctor takes some blood (e.g. from the umbilical cord ) immediately after birth and examines it for genetic changes. In this way, it is possible to detect the disease early and treat it in good time.

diagnosis in pregnancy

In unborn children, the examination for thalassemia (prenatal diagnosis) is carried out using a tissue sample from the placenta .

Doctors recommend expectant parents who know they are carriers of thalassemia to have this prenatal diagnosis done in the first 12 weeks of pregnancy.

Is thalassemia hereditary?

Thalassemias are hereditary. This means that people with thalassemia inherit the genetic defect from their parents and are born with the disease.

Heredity: alpha thalassemia

There are different degrees of severity in alpha thalassemia. A distinction is made between alpha thalassemia minima, minor, intermedia and major. The expression depends on the number of diseased genes that the parents pass on to the child. There are four genes for the alpha chain, two from the mother and two from the father.

A total of four genes are involved in the formation of alpha chains. In the case of alpha thalassemia major, all genes that the child inherited from the parents are defective. It is the most severe form of alpha thalassemia. Children with this form are rarely able to survive and usually die before birth or a few days later. Only in a few cases is it possible to keep the children alive with the help of a stem cell transplant.

People with alpha thalassemia minor or intermediate have inherited two or three defective genes from their parents. They are among the milder forms of alpha thalassemia and usually cause moderate, mild, or no symptoms in those affected.

If only one parent passes on a defective gene to their child, this is referred to as minimal alpha thalassemia. Those affected usually have no symptoms and live without impairment.

Heredity: beta thalassemia

There are also different degrees of severity for beta thalassemia. They are divided into minor, intermedia and major.

Thalassemia major (also called Cooley anemia) is the most severe form. It occurs when both parents pass the genetic defect on to the child.

In the case of beta-thalassemia major, it is necessary to exchange the blood of those affected regularly (about every third to fourth week) by means of infusions. If left untreated, those affected usually develop severe bone deformities. The affected children are also much more susceptible to infections, they are weak and usually do not develop according to their age.

Intermediate beta-thalassemia is an intermediate form. People with this form also inherited the defective genes from both parents. Its symptoms are usually not quite as pronounced as in the major form. They only need blood transfusions occasionally.

In the case of beta thalassemia minor, sufferers have inherited only one defective beta hemoglobin chain gene from one parent. The other parent has passed a functional gene to the child.

People with beta-thalassemia minor usually have no or only mild symptoms of anemia. Usually they do not require any treatment. However, as gene carriers, they are able to pass the thalassemia on to their children.

If both parents have minor beta thalassemia, there is a 25 percent chance that the child will inherit both mutations and develop major or intermediate thalassemia. There is a 50 percent chance that the child will inherit a minor form and there is a 25 percent chance that the child will be healthy.

In order to develop beta thalassemia, both parents must pass their defective genes on to the child. A carrier of the disease has only one defective gene, the other gene is functional. Although he does not get sick, he can pass the gene on to his children.

Where does thalassemia occur?

Thalassemia is also known colloquially as Mediterranean anemia, as it is widespread in Mediterranean countries such as Italy and Greece. However, it also occurs in the Near and Middle East and in parts of Africa and Asia. In Central Europe, thalassemia has spread through global trade links and migration.

Since the 1960s, thalassemia has also occurred in Central and Northern Europe (eg Germany, Austria, France, England, the Netherlands, Belgium and Scandinavia). Thalassemia is now one of the most common blood diseases in children and adolescents here as well.

How common is the disease?

It is estimated that around 500 to 600 people in Germany live with a severe form of thalassemia. Around 200,000 people in Germany suffer from the mild form of thalassemia. In addition, beta thalassemia occurs more frequently than alpha thalassemia.

How is thalassemia treated?

The doctor, usually a specialist (such as a pediatric hematologist), treats thalassemia based on the severity of the condition and the symptoms that are present. Treatment takes place in centers that specialize in the disease. Depending on whether those affected need a blood transfusion, a distinction is now made between transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) therapy for thalassemia.

Non-transfusion dependent treatment

Mild forms of thalassemia usually do not require treatment. During pregnancy, however, it is possible in rare cases for pregnant women to develop severe anemia due to mild thalassemia. They then need regular blood transfusions to protect mother and child.

Transfusion dependent treatment

The doctor replaces the blood of transfusion-dependent people (eg with thalassemia major or intermediate) with regular blood transfusions. Depending on the severity of the thalassemia, this usually occurs about every second to third week, usually for a lifetime.

The additional blood transfusions often lead to an excess of iron. In these cases, the doctor prescribes medication that removes the excess iron from the body (so-called chelators or iron chelators). The doctor in the hospital injects this under the skin (subcutaneously) or the patient takes tablets at home.

stem cell transplant

It is possible to cure thalassemia major with stem cell transplantation. However, this presupposes that there is a suitable donor for the person concerned.

gene therapy

Gene therapy for transfusion-dependent beta-thalassemia has been available since 2019. The therapy treats the causative gene defect and gives those affected the chance to live without transfusions for the rest of their lives.

This new treatment involves inserting an intact gene, which is capable of making healthy hemoglobin, into the patient’s blood stem cells. To do this, stem cells are first removed from the patient’s bone marrow and treated with a drug. After that, the affected person gets back their own stem cells (with their genes intact), which now produce healthy red blood cells and normal blood pigment.

The European Medicines Agency (EMA) has approved the treatment for those affected from the age of twelve who are suitable for this special form of therapy. Gene therapy is currently only possible in Germany. Very few patients are currently being treated with it.

diet and lifestyle

People with thalassemia are able to positively influence the course of their disease with the right diet and an adapted lifestyle. Please note the following:

  • Eat a balanced diet.
  • Avoid foods with extremely high iron content (eg liver).
  • Consume sufficient calcium through food (e.g. milk, yoghurt, cheese, spinach leaves, broccoli).
  • Don’t drink alcohol.
  • Get regular exercise (about three to four hours of exercise like brisk walking, jogging , or cycling per week).

What are the symptoms of thalassemia?

How severe the symptoms are depends on how much of the hemoglobin is pathologically altered. People with a mild form of thalassemia usually have no or hardly any symptoms.

If left untreated, babies with a severe form of thalassemia will develop health problems as early as the fourth or fifth month of life.

anemia

People who have thalassemia major or intermediate initially show typical symptoms of anemia:

  • They are pale or have yellowish skin.
  • You are tired all the time.
  • you feel dizzy
  • You have a headache.
  • You have an accelerated heartbeat.
  • During physical activity, they quickly become short of breath.
  • They often have an enlarged liver and spleen.
  • Their development is often disturbed.

At first glance, thalassemia resembles iron deficiency anemia. However, the iron level is low in iron deficiency, while it is usually normal in thalassemia.

Later, or if treatment is inadequate, those affected often experience severe side effects. These include, for example:

  • bone deformities
  • Frequent infections
  • heart problems
  • diabetes mellitus
  • osteoporosis

bone changes

People with thalassemia major or intermediate often also show altered bone growth:

  • The cranial bone enlarges.
  • Forehead, upper jaw and cheekbone are protruding.
  • Ribs and vertebral bodies are bent.
  • You have an increased risk of fractures.
  • You have bone pain.
  • You get osteoporosis.

excess iron

People with severe forms of thalassemia often store too much iron in the body (iron overload), which can no longer be broken down by itself. This may damage the organs (secondary haemochromatosis). The increased iron comes, among other things, from the additional blood that those affected receive regularly via infusions.

In addition, the body considers anemia to be an iron deficiency and tries to compensate for this by absorbing more iron from food. In addition, the body produces excessive amounts of blood cells. The liver and spleen then work at full speed to break them down again.

The excessive iron concentration causes other symptoms in those affected, such as:

  • heart muscle weakness (heart failure)
  • cardiac arrhythmias
  • liver dysfunction
  • Diabetes (diabetes mellitus)
  • short stature
  • Delayed puberty
  • Underactive thyroid (hypothyroidism)
  • Disorders of vitamin D metabolism

When to the doctor?

Since severe forms of thalassemia often show up in the first few months of life, it is important that parents see a pediatrician as soon as possible when the first signs (eg paleness) appear.

How to prevent?

Doctors advise people who know that they carry the gene for thalassemia to visit a human genetics counseling center before a planned pregnancy or if they want to have children.

Trained specialists there use a genetic blood test to determine possible genetic risks associated with pregnancy in couples.

People with a family history of thalassemia are also advised to seek counseling before becoming pregnant.

To prevent life-threatening infections, doctors also recommend that children with thalassemia be vaccinated according to the current vaccination schedule, just like healthy children. In some cases it is necessary to regularly treat children with thalassemia with certain antibiotics. These help prevent serious bacterial infections that people with thalassemia are particularly susceptible to.

Regularly measuring body temperature helps to identify infections as early as possible and to treat them as quickly as possible. If you have a fever of more than 38.5 degrees Celsius, you should see a doctor immediately. It’s possible that an infection is the cause.

It is also particularly important that those affected have regular medical check-ups. This is the only way to carefully monitor the course of the disease and to identify and treat complications at an early stage.

Is thalassemia curable?

Complete healing of thalassemia is currently only possible with stem cell transplantation or gene therapy. The life expectancy and quality of life of those affected has increased continuously thanks to new drugs, improved treatment and better education.

What is the prognosis for thalassemia?

People with a mild form of thalassemia (alpha or beta thalassemia minor) have a normal life expectancy. As a rule, those affected are able to live without impairments.

In more severe forms, it is often just as possible to achieve an almost normal life expectancy with the right and early treatment (e.g. regular blood transfusions). However, lifelong, continuous and intensive therapy is then necessary.

Sometimes the condition can be cured with stem cell transplantation and, in rare cases, gene therapy.

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