Autosomal recessive inherited disorders of haemoglobin, causing reduced globin chain synthesis, resulting in impaired haemoglobin production

Aetiology

• Genetic defect
  • Defects in alpha-globin chains leads to alpha thalassaemia
  • Defects in the beta-globin chains leads to beta thalassaemia
  • Both conditions are autosomal recessive
• Geographically, thalassaemias are prevalent in populations originating from Mediterranean Europe, Central Africa, the Middle East, the Indian subcontinent and Southeast Asia
  • Having thalassaemia trait is believed to confer some protection against falciparum malaria

Alpha thalassaemia

Pathophysiology

• Deletion of one ⍺+ (-⍺) or both ⍺0 (- -) alpha genes from chromosome 16 results in defects in alphaglobin chains
• ⍺ chains present in HbA, HbA2 and HbF are all affected

Consequences

• Results in inadequate Hb production → microcytic hypochromic anaemia
• If severe:
  • Unbalanced accumulation of globin chains which are toxic to the cell
  • Ineffective erythropoiesis
  • Haemolysis

Classification

• Unaffected = 4 normal ⍺ genes (⍺⍺/⍺⍺)
• ⍺ thalassaemia trait = one or two ⍺ genes missing
  • Asymptomatic carrier state, no Rx needed
  • Microcytic hypochromic red cells with mild anaemia
  • Important to distinguish from iron deficiency - ferritin will be normal
• HbH disease = three defective copies so only one alpha gene left (- -/-⍺)
  • Moderate to severe anaemia with very low MCV and MCH
  • Excess β chains form tetrameres (β4) called HbH
  • Common in SE asia
• Hb Barts hydrops fetalis = no functional ⍺ genes (- -/- -)
  • Minimal or no ⍺ chain production → HbF and HbA can’t be made
  • No alpha chains to bind to so tetramers of Hb Barts (𝛾4) and HbH (β4) produced
  • Incompatible with life - antenatal screening to avoid risk

Clinical features

• Jaundice
• Fatigue
• Facial bone deformities