Thalassemia

Thalassemia is an inherited blood disorder caused by alteration in the synthesis of one or more of the chains that composed hemoglobin.

Hemoglobin is a protein found in red blood cells (RBCs) that is the responsible to transport oxygen to cells and tissues of the body. When there is not enough hemoglobin, red blood cells cannot carry enough oxygen to the cells and a disorder called anemia appears. Anemia is related to symptoms such as fatigue, weakness, or headache.

Therefore, thalassemia is a type of anemia classified within the group of hereditary anemias.

Hemoglobin is a protein made up of four polypeptide chains called globins: two alpha globin chains and two beta globin chains.

Thalassemia is the consequence of a genetic mutation that results in reduced or absent production of globins.

Depending on the type of globin that is affected, thalassemia can be classified into:

• Alpha thalassemia: Where the alpha globin chain is affected. Four genes, two on each copy of chromosome 16, regulate the synthesis of alpha globin. There are different types of alpha thalassemia depending on the amount of affected genes:
  • Alpha thalassemia silent carrier: Produced by one missing or damaged gene
  • Alpha thalassemia minor or trait, also called alpha thalassemia carrier: Produced by two missing or damaged genes
  • Hemoglobin H disease: When there are three missing or damaged genes
  • Hemoglobin Bart, alpha thalassemia major or Bart's hydrops fetalis: All four genes are missing or damaged.
• Beta thalassemia: Where the beta globin chain is affected. The synthesis of beta globin chains is regulated by two genes on each copy of chromosome 11.
  • Beta thalassemia minor, beta thalassemia trait or Rietti-Greppi-Micheli disease: When there is a mutation in one of the genes
  • Beta Thalassemia intermedia: When there is a mutation in both genes
  • Cooley's anemia or beta thalassemia major: When there is a severe alteration (many missing DNA fragments) in both genes.

Thalassemia is a hereditary disorder, meaning it is transmitted from parents to offspring.

Thalassemia is caused by mutations in certain genes: alpha thalassemia is due to mutations in genes on chromosome 16, while beta thalassemia is due to mutations in genes on chromosome 11.

Some people are asymptomatic, but they may be carriers of the disorder.

It is estimated that clinical manifestations of thalassemia have an incidence of 2.5 cases per 1000 people. Approximately 5% of the world's population carries trait genes for hemoglobin disorders, although they might not experience any symptoms.

Alpha thalassemia is more common in Asia and Africa, while beta thalassemia has a higher incidence in the Mediterranean area.

Thalassemia causes red blood cells being destroyed in large numbers due to erythrocyte osmotic fragility. Therefore, people with thalassemia tend to have anemia with symptoms such as fatigue, weakness, headache, dizziness, etc.

The severity of the disorder depends on the type of thalassemia:

Alpha thalassemia

• Alpha thalassemia silent carrier: It may go unnoticed without any symptoms.
• Alpha thalassemia minor or trait: It does not usually produce symptoms. Mild anemia may be detected.
• Hemoglobin H disease
  • Moderate anemia
  • Enlarged spleen (splenomegaly)
• Hemoglobin Bart or alpha thalassemia major: It is a condition characterized by hydrops fetalis and other clinical signs, causing the baby to die soon after birth. Since this severe condition leads to a lack of hemoglobin, oxygen is not transported to cells and tissues of the body.

Beta thalassemia

• Beta thalassemia minor: People may not show any symptoms. If they do, they are usually:
  • Moderate anemia
  • Enlarged spleen (splenomegaly)
  • Venous crural ulcers
• Beta Thalassemia intermedia
  • Anemia is common when there are present other diseases or infections
• Cooley's anemia or beta thalassemia major: Children are born healthy, but deteriorate rapidly within a few months due to severe anemia. They usually present:
  • Abnormal face structure with Asian features, abnormally prominent forehead and abnormal skull structure
  • Paleness
  • Abdominal swelling
  • Fever spikes with no apparent cause
  • Enlarged liver and spleen (hepatosplenomegaly)
  • Wide and flat ribs

Mild forms of thalassemia do not require treatment. For moderate or severe forms of thalassemia, treatment may include:

• Blood transfusions
• Administration of folic acid to increase the production of red blood cells

For Cooley's anemia or beta thalassemia major, continuous monitoring and regular blood transfusions are required. Spleen removal may also be necessary. Bone marrow transplantation is a highly effective treatment option.

Blood transfusions can lead to a large accumulation of iron in the body, which may be harmful. To prevent iron accumulation, Deferoxamine may be prescribed.