(A&E)

Overview

• HbF → 2 alpha globin + 2 gamma globin
• HbA → 2 alpha globin + 2 beta globin
• HbA2 → 2 alpha globin + 2 delta globin
• Haemoglobinopathies → group of recessively inheritied conditions affecting the haemoglobin component of blood
  • Change in Structure and Quality of Haemoglobin ⇒ haemoglobin variants such as HbS (sickle cell disease), HbO, HbE
  • Reduction in Quantitiy of Haemoglobin ⇒ alpha or beta thalassaemia (reduced globin synthesis)

Thalassaemia (Autosomal Recessive):

• Beta Thalassaemia → most commonly seen in people of mediterranean descent
• Αlpha Thalassaemia → most commonly seen in people of asian and african descent
• Cause ⇒ gene mutations
  • Beta Thalassaemia → beta-globin chains are coded by a total of two alleles, so there are two main forms of the disease. Beta thalassaemia minor (one defective allele) or beta thalassaemia major (two defective alleles)
    • HbA (2 alpha and 2 beta chains) can not be produced, hence rise in HbA2 and HbF
  • Αlpha Thalassaemia → α-globin chains are coded by a total of four alleles, so there are four forms of the disease. Silent carrier (one defective allele), alpha thalassaemia trait (two defective alleles), haemoglobin H disease (three defective alleles), haemoglobin bart disease (four defective alleles).

Making Diagnosis

Clinical Features:

• Beta Thalassaemia:
  • Minor → mild microcytic hypochromic anaemia. Asymptomatic.
  • Major → severe haemolytic anaemia, hepatosplenomegaly, skeletal deformities
• Αlpha Thalassaemia:
  • Silent Carrier → asymptomatic. No anaemia.
  • Αlpha Thalassaemia Trait → microcytic hypochromic red cells. No anaemia.
  • Haemoglobin H (HbH) Disease → microcytic hypochromic anaemia with splenomegaly
  • Haemoglobin Bart Disease → intrauterine death