Because Mediterranean anemia (thalassemia) is more common in Mediterranean countries, it is called by this name, but this disease is also a common genetic blood disorder in Africa and Southeast Asian countries. Mediterranean anemia (beta-thalassemia) is a preventable, hereditary blood disorder passed from parents to children, and its symptoms include weakness, easy fatigue, palpitations, and shortness of breath. Although there are different treatment options for the disease, the permanent and definitive treatment method is bone marrow transplantation!
Mediterranean anemia, also known as thalassemia major, is a genetically inherited blood disorder that affects our red blood cells. Since it is genetically inherited, consanguineous marriages increase the risk of this disease.
Anemia is caused by changes in the structure and number of a molecule called hemoglobin, which is found in our red blood cells and plays a role in transporting oxygen throughout our bodies.
Pediatric Hematology Specialist Prof. Dr. Barış Malbora explains the disease as follows:
"In case of a deficiency or defect in hemoglobin production, the oxygen transport function cannot be performed adequately, and a decrease in oxygen in tissues and organs can lead to complaints such as pallor, weakness, easy fatigue, palpitations, and developmental delay. Depending on the type of defect in this molecule, the disease is referred to by various names and shows different clinical features. In our country, the most common cause of hemoglobin disorders is beta-thalassemia (Mediterranean anemia). However, there are also rarer hemoglobin disorders such as sickle cell anemia and alpha-thalassemia."
HOW COMMON IS THALASSEMIA IN OUR COUNTRY AND AROUND THE WORLD?
Pediatric Hematology Specialist Prof. Dr. Barış Malbora states that while alpha-thalassemia is commonly seen in Central Asia, beta-thalassemia, or more commonly known as Mediterranean anemia, is more prevalent in our country. He says, "3% of the world's population is a beta-thalassemia carrier, and 5-10% of the Southwest Asian population is an alpha-thalassemia carrier."
Stating that there are approximately 1,400,000 beta-thalassemia carriers and around 4,500 beta-thalassemia patients in Turkey, Pediatric Hematology Specialist Prof. Dr. Barış Malbora says, "Thalassemia carrier status is very common in our country, especially in the Mediterranean, Aegean, and Marmara regions. However, due to inter-regional migration, the disease is also known to be seen in other parts of our country. Across Turkey, one in every 40-50 people carries the genes that can lead to thalassemia; in Antalya, Adana, and the Southeastern Anatolia Region, it's one in every 10 people."
HOW DOES MEDITERRANEAN ANEMIA (THALASSEMIA MAJOR) OCCUR?
For Mediterranean anemia to occur, at least one of the two parents must be a carrier of the disease or have the disease. Pediatric Hematology Specialist Prof. Dr. Barış Malbora warns that due to the genetic inheritance of the disease, there is a 25% chance of a child having the disease if both partners are carriers.
However, thalassemia, which is a major health problem worldwide and one of the most common genetic diseases in our country, can be detected with screening tests. For this reason, Mediterranean anemia is called a 'preventable disease.'
Thalassemia screening is performed with simple tests taken from couples before marriage. If neither partner has the disease gene, they do not need to fear this disease. Their children will never have this disease. If one of the partners is a carrier, there is no risk of having a sick child. In this case, the worst-case scenario is that they might have a child who is a carrier like them. If both the mother and father are carriers, this is the biggest risk factor for the disease. In this case, for every child they have, there is a 25% chance of being normal, a 50% chance of being a carrier, and a 25% chance of having the disease (thalassemia major; Mediterranean anemia).
The detection of carrier status in the mother and father does not prevent them from having a healthy child. When couples want to have children, they should first be followed by a specialist in obstetrics and gynecology. In this case, healthy embryos obtained with the Preimplantation Genetic Diagnosis (PGD) method can lead to the birth of healthy children through insemination or in vitro fertilization.
WHAT ARE THE TYPES OF MEDITERRANEAN ANEMIA?
THALASSEMIA MAJOR
Pediatric Hematology Specialist Prof. Dr. Barış Malbora states that the most serious form of the disease is beta-thalassemia and explains it as follows: "It usually appears after the baby turns 6 months old and can lead to organ damage in the years to come. Once the disease is detected, it is attempted to be controlled with blood transfusions.
Patients carry both thalassemia genes inherited from their mother and father. In addition to severe anemia, thalassemia patients may experience jaundice, swelling in the abdomen due to enlarged liver and spleen, gallstones, weakness, fatigue, susceptibility to infections, stunted growth and development, bone expansion and thinning, a flattened nose bridge, and an abnormal facial appearance with forehead and other facial bone protrusions. In girls, the onset of menstruation may be delayed. Patients need lifelong blood transfusions and medications to remove excess iron from the body. In patients with thalassemia major, ulcers on the legs and darkening of the skin can be seen in advanced age. If the excessive iron accumulated in the body due to blood transfusions is not removed in patients undergoing thalassemia treatment, problems such as heart failure, hormonal system disruption, bone deformities, and spleen enlargement can occur. Today, the definitive treatment for this disease is bone marrow transplantation."
THALASSEMIA INTERMEDIA
This is an intermediate form of the disease. Both parents are carriers, but unlike thalassemia major, the genetic changes lead to moderate anemia. Patients usually do not need blood transfusions. Symptoms become noticeable between the ages of 2 and 4. There can be jaundice, enlarged spleen and liver, and stunted growth. They may need blood transfusions during infections.
THALASSEMIA MINOR (THALASSEMIA CARRIER)
Individuals have one of the two thalassemia genes, but the other gene is healthy. Therefore, the person is healthy except for mild anemia. However, if the person has a child with another carrier, the child has a chance of having thalassemia. This mild anemia does not negatively affect the person's quality of life and does not require treatment. Since the risk of thalassemia is high, especially in consanguineous marriages, it is very important for these individuals to get the necessary tests done before marriage. Another importance of this condition is that thalassemia carrier status can be easily confused with anemia due to iron deficiency. The blood count markers show a great similarity between thalassemia carrier status and iron deficiency anemia. To distinguish between these two conditions, it is usually sufficient to perform iron deficiency tests on the person.
THALASSEMIA SILENT CARRIER
The symptoms are the same as in thalassemia minor, but hemoglobin electrophoresis is normal. It is unfortunately not possible to detect these individuals with screening tests. The diagnosis is made with genetic analysis.
HOW IS MEDITERRANEAN ANEMIA DIAGNOSED?
In families known to have a patient or a carrier, a diagnosis can be made with screening tests during pregnancy. Thalassemia can also be detected with a newborn blood test (heel stick test).
A diagnosis is made in children who show symptoms of thalassemia after birth or are brought in due to anemia. Carriers are mildly anemic but do not need treatment. Patients have severe anemia; a definitive diagnosis is made by performing a complete blood count, hemoglobin electrophoresis, and genetic tests on the mother, father, and child.
For individuals suspected of having Mediterranean anemia, a complete blood count and peripheral smear (microscopic examination of blood cells) should be done initially. If suspicion of the disease continues after these tests, more advanced tests such as hemoglobin electrophoresis and genetic screening (DNA analysis) should be used. It is possible to make a definitive diagnosis with these tests. Especially in cases where both partners are carriers, genetic counseling should be given, and pre-pregnancy tests should be done.
HOW IS MEDITERRANEAN ANEMIA (THALASSEMIA) TREATED?
Since thalassemia affects various tissues of the body, its treatment should be carried out with the participation of many specialist physicians. Patients are followed and their treatments are planned by specialists in Hematology, Cardiology, Endocrinology, Psychiatry, and pediatric surgeons. The cooperation between the physician, patient, and patient's family is very important for the regular continuation of the treatment and for not neglecting the necessary tests.
BLOOD TRANSFUSION
People with Mediterranean anemia, if they do not undergo a bone marrow transplant, need regular blood transfusions throughout their lives. While blood is needed every 2 to 3 months after the initial diagnosis, the need for blood increases to a frequency of every 2 to 3 weeks in some patients as the years go by. In situations where the need for blood transfusion increases, the entire or a part of the spleen may need to be removed to reduce this need. In untreated patients, conditions such as skeletal deformities, pathological bone fractures, liver fibrosis and cirrhosis, diabetes, underactive thyroid and parathyroid glands, and sexual development disorders can occur. As a result of iron accumulation in the heart muscle, heart rhythm disorders, heart failure, and increased pulmonary pressure can develop. For this reason, it is important to monitor the person for possible hormonal problems and to have regular imaging tests of their organs such as the gallbladder, liver, and heart.
BONE MARROW TRANSPLANTATION
Today, the definitive treatment for Mediterranean anemia is a bone marrow transplant. As a result of a successful transplant, the patient can continue their life without blood support and its side effects.
The most suitable donor for a thalassemia patient is the patient's sibling. The fact that the stem cell donor is a thalassemia carrier is not an obstacle for the transplant. However, after the transplant from a thalassemia carrier, the patient will continue their life as a thalassemia carrier. After the transplant, their blood count will be lower than that of healthy people. However, this low count will not negatively affect the patient's life. The patient's tissue types must be compatible for the body not to reject the bone marrow. The sibling is the most suitable donor for this. Compatibility is determined by certain tests. After the transplant, since the healthy marrow will produce red blood cells containing normal hemoglobin, there may be no need for blood transfusions. In patients who do not have a suitable sibling donor, parents and relatives can be screened. The absence of a donor within the family and relatives does not mean the end of the road for these patients. These patients are first offered the option of having a healthy child with a compatible tissue type through in vitro fertilization. If the parents accept, they can have a child with the in vitro fertilization method and a stem cell transplant can be performed on the patient from this sibling. If this option is not accepted, a bone marrow transplant can be successfully performed by obtaining well/fully compatible donors from the TÜRKÖK and global stem cell banks.
The success rate of stem cell transplantation varies from patient to patient, depending on the patient's age and whether they have additional health problems. This rate ranges from 60% to 95%. The success of the transplant is higher in patients who have the transplant at an early age, who have not received many blood transfusions, who have low iron accumulation in their bodies, and who have not developed organ failure.