Genetics · MU Sofia

16. Genetic anemias: thalassemias.

Explains thalassemias as inherited, autosomal recessive anaemias caused by reduced or absent globin chain synthesis, contrasting them with sickle cell disease. It then covers normal haemoglobin synthesis, the chain-imbalance pathogenesis, and separate sections on alpha and beta forms, including a stepwise breakdown of alpha-thalassemia by number of deleted genes. Clinical features, laboratory findings such as electrophoresis patterns, and management with transfusion, chelation and transplantation close the note.

Inside: 8 sections · 7 labelled pictures · 15 flashcards · 4 min

Topic 16 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 8 sections, about 547 words (4 min of reading), with 15 flashcards.

In this note

  1. Genetic Anemias: Thalassemias
  2. Introduction
  3. Normal Hemoglobin Synthesis
  4. Pathogenesis
  5. Types of Thalassemia
  6. Clinical Features
  7. Laboratory Findings
  8. Management

Introduction

Thalassemias are a group of inherited anemias caused by reduced or absent synthesis of globin chains that make up hemoglobin.

Unlike sickle cell disease (a qualitative defect in Hb structure), thalassemias are quantitative defects of hemoglobin production. The imbalance between α- and β-chain synthesis leads to unstable hemoglobin, destruction of red cell precursors in the bone marrow, and chronic hemolytic anemia.

They are especially prevalent in the Mediterranean, Middle East, Africa, and Asia, where the carrier state is common because it provides partial protection against malaria. Inheritance is autosomal recessive.

Normal Hemoglobin Synthesis

  • Adult hemoglobin (HbA) = α₂β₂.
  • α-globin genes → chromosome 16 (2 per chromosome, total 4).
  • β-globin gene → chromosome 11 (1 per chromosome, total 2).
  • A balanced production of α- and β-chains is essential.
  • Any defect → excess of the opposite chain → precipitation, RBC damage, and anemia.

Pathogenesis

The key mechanism in both α- and β-thalassemia is imbalance of globin chain synthesis:

  1. 1. Mutation causes ↓ synthesis of α- or β-globin.
  2. 2. Excess free chains precipitate inside RBC precursors.
  3. 3. This triggers oxidative damage to membranes and apoptosis of erythroblasts → ineffective erythropoiesis.
  4. 4. The RBCs that survive are fragile and undergo hemolysis in the spleen.
  5. 5. Severe anemia stimulates bone marrow expansion and extramedullary hematopoiesis → skeletal deformities, hepatosplenomegaly.
  6. 6. Iron overload occurs due to ↑ intestinal absorption + transfusions → damage to heart, liver, and endocrine glands.

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