Lesson 3 of 5
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September 5, 2022

Genetic diseases of defective globin chain of hemoglobin with impairment of production. Result lead to abnormal globin precipitation destruct the erythrocyte membrane, hemolysis occur. Microcytic anemia.

Thalassemia is a genetic disease that is passed down to a person from his parents. There are two main types of it namely alpha thalassemia and beta thalassemia. It is more common among people of Italian, Greek, Turkish, Middle Eastern, South Asian, and African descent.

Normal hemoglobin is composed of two pairs of globin chains, alpha (α) and beta (β). Each globin chain is attached to an iron-containing heme moiety. This is called HbA. The β-globin chains are encoded by a gene on chromosome 11. The α-globin chains are encoded by two closely linked genes on chromosome 16.

HbA, HbA2, HbF are found in adults. HbF is found in infants and children.
At age 6-12 months HbA replaces the HbF.
Type Globin ChainsPercentage
HbATwo alpha (α) + two beta (β)95%-98%
HbA2Two alpha (α) + two delta (δ)2%-3%
HbFTwo Alpha (α) + Two Gamma (γ)0.8%-2%

Cause of the disease

Thalassemia patients have low or complete absence of α or β globins. Hemoglobin molecules are composed of alpha and beta chains that are susceptible to mutations. In thalassemia, the production of alpha or beta chains decreases, resulting in alpha-thalassemia or beta-thalassemia. Precipitation of affected globin destroys the membrane of erythrocytes. Anemia occurs due to this destruction of red blood cells.


Alpha thalassemia is most common in people of Southeast Asian, Middle Eastern, Chinese, and African descent. Each chromosome 16 contains two separate alpha globin gene loci so each has four alpha gene alleles. The severity of alpha thalassemia is determined by the absence of these four genes.

  • 1 gene is destroyed – the disease will not manifest. They will be asymptomatic carriers, normal Hb, normal MCV
  • 2 genes are destroyed – Mild Anemia
  • 3 genes are destroyed – Hemoglobin H disease (HbH) – Moderate Anemia, splenomegaly
  • 4 genes are destroyed – Hb Barts Disease (Hydrops fetalis) the baby dies in utero or dies at birth.


Autosomal, recessive. Mutation in the β globin genes on chromosome 11.

  • β+ – Decrease production
  • βo – Absence
  • β – Unaffected


  • FBC,
  • MCV,
  • Iron,
  • HbA2, HbF
  • Hemoglobin electrophoresis.
  • Target cell in the blood film.

β thalassemia major: βoo

Severe anemia as there were no beta chain produced. A mutation occurs in both the alleles (genotype βo / βo). No functional β chains are produced and thus hemoglobin A cannot be formed.

  • Skull bossing due to extra medullary hematopoiesis.
  • Hepatosplenomegaly.
  • Hair-on-end sign in Skull X-ray.
  • Impaired growth – Hypogonadal dwarf,
  • Endocrine failure

β thalassemia intermedia: β+ / βo or β+ / β+

In which the genotype is β+ / βo or β+ / β+. Hemoglobin A is produced in small amounts. Do not require transfusion. Splenomegaly.

β thalassemia minor: β / βo or β / β+

Genotype β / βo or β / β+. Because only one of these alleles is affected by the mutation, the disease is often undetected in them, they act as carrier. But anemia can occur.

Treatment (thalassemia major)

  • Eat a healthy diet, Folate supplements
  • Regular life-long Blood transfusion
  • Chelation therapy – deferoxamine to prevent iron overload as a result of transfusion
  • Splenectomy
  • Allogenic bone marrow transplant or Stem cell