Thalassemia are forms of inherited (genetic) autosomal recessiveblood disorders that originated in the Mediterranean region.. In thalassemia, the disease is caused by the weakening and destruction of red blood cells. Thalassemia is caused by variant or missing genes that affect how the body makes hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen. People with thalassemia make less hemoglobin and fewer circulating red blood cells than normal, which results in mild or severe anemia. Thalassemia can cause significant complications, including iron overload, bone deformities and cardiovascular illness. However, this same inherited disease of red blood cells may confer a degree of protection against malaria, which is or was prevalent in the regions where the trait is common. This selective survival advantage on carriers (known as heterozygous advantage) may be responsible for perpetuating the mutation in populations.

There are an estimated 60-80 million people in the world carrying the beta thalassemia trait alone. This is a very rough estimate; the actual number of thalassemia major patients is unknown due to the prevalence of thalassemia in less developed countries. Countries such as India and Pakistan are seeing a large increase of thalassemia patients due to lack of genetic counseling and screening. There is growing concern that thalassemia may become a very serious problem in the next 50 years, one that will burden the world's blood bank supplies and the health system in general.


As this conditionoriginated in the Mediterranean region thus the name of this condition derives from the GreekThalassa (sea), and haema ( blood). The term was first used in 1932.


Normally, hemoglobin is composed of four protein chains, two a and two ß globin chains arranged into a heterotetramer. In thalassemia, patients have defects in either the a or ß globin chain causing production of abnormal red blood cells.

Types of Thalassemias

The two main types of thalassemia

The thalassemias are classified according to which chain of the hemoglobin molecule is affected. Hemoglobin includes two kinds of protein chains called alpha globin chains and beta globin chains. In a thalassemias, production of the a globin chain is affected, while in ß thalassemia production of the ß globin chain is affected.Alpha and beta thalassemias have both mild and severe forms.

Alpha thalassemia

When one or more of the four genes needed for makingthe alpha globin chain of hemoglobin are variant ormissing. Moderate to severe anemia results when morethan two genes are affected. The most severe form of alpha thalassemia is known as alpha thalassemia major.It can result in miscarriage.

  • Alpha thalassemia “silent carrier”
  • Mild alpha thalassemia, also called alpha thalassemia minor or alpha thalassemia trait
  • Hemoglobin H disease
  • Hydropsfetalis, or alpha thalassemia major

Four genes are involved in making the alpha globin part of hemoglobin—two from each parent. Alpha thalassemia occurs when one or more of these genes is variant or missing.

Beta thalassemia

When one or both of the two genes needed for making the beta globin chain of hemoglobin are variant. The severity of illness depends on whether one or both genesare affected and the nature of the abnormality. If both genes are affected, anemia can range from moderate to severe. The severe form of beta thalassemia is also known as Cooley’s anemia.

  • Beta thalassemia minor, also called thalassemia minor or thalassemia trait or carrier
  • Beta thalassemia intermedia, also called thalassemia intermedia or mild Cooley’s anemia
  • Beta thalassemia major, also called thalassemia major or Cooley’s anemia or Mediterranean anemia
  • Two genes are involved in making the beta globin part of hemoglobin—one from each parent. Beta thalassemia occurs when one or both of the two genes are variant.
  • If one gene is affected, a person is a carrier and has mild anemia. This condition is called beta thalassemia trait, or beta thalassemia minor.
  • If both genes are variant, a person may have moderate anemia (beta thalassemia intermedia, or mild Cooley’s anemia) or severe anemia (beta thalassemia major, or Cooley’s anemia).

Who Is At Risk for Thalassemia?

  • Thalassemia is passed from parents to children through their genes.
  • Thalassemia affects both males and females.
  • Beta thalassemias affect people of Mediterranean origin or ancestry (Greek, Italian, Middle Eastern) and people of Asian and African descent.
  • Alpha thalassemias mostly affect people of Southeast Asian, Indian, Chinese, or Filipino origin or ancestry.

What Are the Signs and Symptoms of Thalassemia?

  • The symptoms of thalassemia depend on the type and severity of the disease. Symptoms occur when not enough oxygen gets to various parts of the body due to low hemoglobin and a shortage of red blood cells in the blood (anemia).
  • “Silent carriers” and persons with alpha thalassemia trait or beta thalassemia trait (also called carriers) usually have no symptoms. Those with alpha or beta thalassemia trait often have mild anemia that may be found by a blood test.
  • In more severe types of thalassemia, such as Cooley’s anemia, patient may present with following signs and symptoms, though not limited to:
    1. Anaemia
    2. Fatigue (feeling tired) and weakness
    3. Pale skin or jaundice (yellowing of the skin)
    4. Protruding abdomen, with enlarged spleen and liver
    5. Dark urine
    6. Abnormal facial bones and poor growth
    7. Expanded marrow space
    8. Leg ulcers
    9. Cholelithiasis
    10. Bone changes and fractures
    11. Growth failure
  • Babies with all four genes affected (a condition called alpha thalassemia major, or hydropsfetalis) usually die before or shortly after birth

How Is Thalassemia Diagnosed?

Usually diagnosed in early childhood because of signs and symptoms, including severe anemia. Some people with milder forms of thalassemia may be diagnosed after a routine blood test, including a complete blood count (CBC) and special hemoglobin studies. Doctors suspect thalassemia if a child has anemia and is a member of an ethnic group that is at risk for thalassemia.

  • Family genetic studies are also helpful in diagnosing thalassemia.
  • Prenatal testing can determine if an unborn baby has thalassemia and how severe it is likely to be.

How Can Thalassemia Be Prevented?

  • Although thalassemia cannot be prevented, it can be identified before birth by prenatal diagnosis.
  • People who have or believe that they may carry the thalassemia genes can receive genetic counseling to avoid passing the disorder to their children.

Thalassemia has an autosomal recessivepattern of inheritance

If two people with beta thalassemia trait (carriers) have a baby, one of three things can happen:

  • The baby could receive two normal genes (one from each parent) and have normal blood (1 in 4 chance, or 25 percent).
  • The baby could receive one normal gene from one parent and one variant gene from the other parent and have thalassemia trait (2 in 4 chance, or 50 percent).
  • The baby could receive two thalassemia genes (one from each parent) and have a moderate to severe form of the disease (1 in 4 chance, or 25 percent).

How Is Thalassemia Treated?

Blood Transfusion

  • Severe forms of thalassemia are treated by regular blood transfusions. A blood transfusion, given through a needle in a vein, provides blood containing normal red blood cells from healthy donors. In thalassemia treatment, blood transfusions are done on a schedule (often every 2–4 weeks) to keep hemoglobin levels and red blood cell numbers at normal levels. Transfusion therapy can allow a person with severe thalassemia to feel better, enjoy normal activities, and live longer.
  • Transfusion therapy, while lifesaving, is expensive and carries a risk of transmitting viral and bacterial diseases (for example, hepatitis). Transfusion also leads to excess iron in the blood (iron overload), which can damage the liver, heart, and other parts of the body. To prevent damage, iron chelation therapy is needed to remove excess iron from the body.


Mild thalassemia : people with thalassemia traits do not require medical or follow-up care after the initial diagnosis is made. People with ß-thalassemia trait should be warned that their condition can be misdiagnosed for the common iron deficiency anemia. They should avoid routine use of iron supplements;yet iron deficiency can develop during pregnancy or from chronic bleeding. Counseling is indicated in all persons with genetic disorders, especially when the family is at risk of a severe form of disease that may be prevented.

Severe thalassemia : People with severe thalassemia require medical treatment. A blood transfusion regimen was the first measure effective in prolonging life.

Multiple blood transfusions can result in iron overload. The iron overload related to thalassemia may be treated via chelation therapy with the medications deferoxamine, deferiprone or deferasirox. These treatments have resulted in improved life expectancy in those with thalassemia major.

Bone marrow transplant

Bone marrow transplantationmay offer the possibility of a cure in young people who have an HLA-matched donor.Success rates have been in the 80-90% range. The best results are with very young patients.Mortality from the procedure is about 3%.


Iron overload: People with thalassemia can get an overload of iron in their bodies, either from the disease itself or from frequent blood transfusions. Too much iron can result in damage to the heart, liver and endocrine system, which includes glands that produce hormones that regulate processes throughout the body. The damage is characterized by excessive deposits of iron. Without adequate iron chelation therapy, almost all patients with beta-thalassemia will accumulate potentially fatal iron levels.

Infection: people with thalassemia have an increased risk of infection. This is especially true if the spleen has been removed.

Bone deformities: Thalassemia can make the bone marrow expand, which causes bones to widen. This can result in abnormal bone structure, especially in the face and skull. Bone marrow expansion also makes bones thin and brittle, increasing the risk of broken bones.

Enlarged spleen: the spleen aids in fighting infection and filters unwanted material, such as old or damaged blood cells. Thalassemia is often accompanied by the destruction of a large number of red blood cells and the task of removing these cells causes the spleen to enlarge. Splenomegaly can make anemia worse, and it can reduce the life of transfused red blood cells. Severe enlargement of the spleen may necessitate its removal.

Slowed growth rates: anemia can cause a child's growth to slow. Puberty also may be delayed in children with thalassemia.

Heart problems: such as congestive heart failure and abnormal heart rhythms (arrhythmias), may be associated with severe thalassemia.

Key points :

  • Thalassemia is an inherited (genetic)blood disorder that causes anemia due to reduced hemoglobin and fewer red blood cells .
  • About 100,000 babies worldwide are born with severe forms of thalassemia each year
  • Thalassemia is caused by variant or missing genes that affect how the body makes hemoglobin.
  • Hemoglobin is the protein in red blood cells that carries oxygen to all parts of the body.
  • People with thalassemia make less hemoglobin and fewer circulating red blood cells than normal. The result is mild or severe anemia
  • In people with thalassemia, the genes that code for hemoglobin are missing or variant (different than the normal genes).
  • Severe forms of thalassemia are usually diagnosed in early childhood and are lifelong conditions.