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Thalassemia is a generic name for a group of hereditary genetic diseases of the red blood cells that result from a defect in the protein chains that make up the hemoglobin.
Thalassemia causes anemia in varying degrees. In its severe form, the disease causes significant anemia, requiring blood transfusions for life.
Similar to other hemoglobinopathies, such as sickle cell anemia, Thalassemia is common in the Mediterranean area; Their prevalence is high in countries such as Greece, Italy, North Africa, and others.
An interesting observation is that carriers of Thalassemia and other hemoglobin diseases have been resistant to malaria in areas where they are common.
Hemoglobin is a four-part molecule made up of four chains of the globine and heme molecule.
Normally, in an adult, the globine chains consist of a pair of alpha chains and a pair of beta chains. This is hemoglobin A - which accounts for about 95% of hemoglobin in red blood cells.
The main component of hemoglobin in the embryo is fetal hemoglobin, hemoglobin F - which has an alpha chain that connects with the gamma chain. The fetal hemoglobin decreases before birth, and in the adult person it is a marginal (minor) component of 2.5-3% of total hemoglobin.
Another marginal component in an adult is hemoglobin A2, which is composed of a combination of alpha chains with delta chains. This hemoglobin accounts for 2.5% of hemoglobin in an adult.
In Thalassemia there is a reduced production of one of the globine chains: alpha (alpha Thalassemia) or beta (beta Thalassemia). The disorder is quantitative - normal hemoglobin is formed, but less than normal.
Symptoms and Signs
There are two major disease conditions in beta Thalassemia:
Carriers of Thalassemia - with whom only one of the gene alleles is pathological. Their clinical symptoms are mild.
Homozygous Thalassemia - received a defective gene from both parents. They are characterized by Thalassemia major, also called Cooly's anemia.
This is a serious disease: the increased destruction of red blood cells causes jaundice, gallstones, severe anemia and hypoxia (lack of oxygen in the blood).
The patient's body tries to compensate for hypoxia; in an attempt to create more blood cells, there is growth of the bone marrow and its invasion into other areas. This causes changes in the bones and the creation of "extramedullary hematopoiesis" - the formation of blood in organs where there is usually no blood formation.
Patients need repeated blood transfusions to survive; this leads to the accumulation of iron, which sinks into various organs of the body (heart, liver, pancreas), causing additional complications.
The complications of the disease:
Due to an attempt to create blood cells in different bones, such as in the skull, a typical appearance develops: cheekbones and forehead are very prominent. This is due to the fact that the medulla of the skull bone is hypertrophy and there is an expansion of the bone marrow.
Increased spleen and liver, because of increased blood damage and blood production in these organs.
Complications as a result of blood transfusions:
Risk of contracting infectious diseases (viral hepatitis, for example(
Iron loading, Hemochromatosis: In each blood vessel there is a significant amount of iron. Due to lack of effective mechanisms to get rid of excess iron, excess iron sinks into various organs and causes great damage. Sinking in the liver will eventually lead to liver cirrhosis.
Iron also sinks in the heart and causes severe cardiomyopathy, which leads to heart failure, which can cause death.
Iron also sinks into endocrine organs, such as the pancreas, thyroid, and parathyroid gland. As a result, there may be diabetes, growth inhibition and the need for hormone replacement therapy.
Diagnosis of carriers (heterozygous(:
For the diagnosis of Thalassemia carriers, blood hemoglobin levels, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) are used. In addition, a hemoglobin electrophoresis test is performed, which measures the different subtypes of hemoglobin in the same person.
In β-Thalassemia, the size of the red blood cells and their degree of concentration are reduced (MCV and MCH are low). In addition, there is an excess level of hemoglobin A2. In a healthy person, hemoglobin A2 accounts for less than 3.5% of hemoglobin. In Thalassemia patients, due to the relative excess in alpha-globine chains, they connect to the Delta chains to form hemoglobin alpha 2 delta 2, hemoglobin A2.
In alpha Thalassemia, the only thing that suspects the carriers is the presence of small blood cells. The size of the blood cells is estimated in the MCV and MCH indices. The MCV is measured in the Femtoliter volume (fL). If the value is below 78, alpha Thalassemia cannot be ruled out. The MCH is considered low if its value is below 26 picograms (pg - picogram). There are no more accurate ways to evaluate, except genetic analysis of DNA.
A large beta-Thalassemia diagnosis is easier because the disease is manifested in severe anemia at the earliest stages of life, and children need early-stage blood transfusions.
Thalassemia carriers need mainly follow-up, counseling and prenatal diagnosis. As well as support for situations where hemoglobin is further reduced, such as pregnancy.
The most important thing is performing prenatal diagnosis in the pregnancy of two carriers. In countries where Thalassemia is common, a marriage license cannot be obtained if both spouses have not undergone a Thalassemia screening. If both parents are carriers, a prenatal diagnosis can be made of the fetus, and if he is ill, it is possible to terminate the pregnancy.
In patients with severe Thalassemia, blood transfusions are needed once every few weeks on a permanent basis.
In addition, treatment is provided for the absorption and removal of iron from the body (iron chelation); Previously the primary treatment was by providing Desferal (Deferoxamine mesylate) in subcutaneous injections. Over time oral preparations were developed, such as Ferriporox (Deferiprone), which was much more convenient for patients. Recently, a product called Exjade (Deferasirox) has been developed orally and is considered to be very effective.
During the course of the follow-up, the complications of the disease and the complications of excess iron, hormonal disorders (hypothyroidism and hypothyroidism) are also treated, delayed growth and impaired sexual development.
The only long term treatment is a bone marrow transplant.