Thalassemia

Thalassemias are a heterogeneous group of hereditary blood disorders characterized by faulty globin chain synthesis resulting in defective hemoglobin, which can lead to anemia

Thalassemia provides partial resistance against malaria.

Beta thalassemia

- most commonly seen in people of Mediterranean descent

Etiology

usually due to point mutations in promoter sequences or splicing sites

β-globin locus - short arm of chromosome 11

In a normal cell, the β-globin chains are coded by a total of two alleles . Thus, there are two forms of the disease.

Beta thalassemia minor (trait): one defective allele

Beta thalassemia major (Cooley's anemia): two defective alleles

Pathophysiology

Inefficient erythropoiesis → anemia

Beta thalassemia minor and major: faulty β-globin chain synthesis → ↓ β-chains→ ↑ γ-,δ-chains → ↑ HbF  and ↑ HbA2

 

Alpha thalassemia

most commonly seen in people of Asian and African descent

Etiology

usually due to deletion of at least one out of the four existing alleles

Inheritance pattern: autosomal recessive

In a normal cell, the α-globin chains are coded by a total of four alleles. 

Thus, there are four forms of the disease. The severity of alpha thalassemia depends on the number of defective α-globin alleles.

- Silent carrier (minima form): one defective allele (-α/αα)

- Alpha thalassemia trait (minor form) -Two defective alleles ,Cis-deletion is common amongst Asian populations, whereas trans-deletions are more common in African populations

- Hemoglobin H disease: three defective alleles

- Hemoglobin Bart disease (major form): four defective alleles

Pathophysiology

Alpha thalassemia major (HbH disease) and Bart disease: faulty α-globin chain synthesis → ↓ α-chains → ↑ β-, γ-chains → ↑ HbH, ↑ Hb-Bart's