23rd May 2023

Beta thalassaemia

Beta thalassaemia is a result of defective beta chain synthesis due to point mutation in the HBB gene on chromosome 11. Two alleles may therefore be affected; the mutated alleles can create either partially functioning, non-functioning, or reduced quantities of beta-globin, resulting in the variations of beta thalassaemia.

Beta thalassaemia can be classified as major, intermedia or minor. However, there has been a shift recently to classify beta thalassaemia as transfusion dependent or non-transfusion dependent.

Beta thalassaemia major (Cooley’s anaemia, transfusion dependent)

• Both beta chain alleles affected resulting in no functional beta chain production.
• Severe haemolytic anaemia requiring regular blood transfusions.
• Symptoms manifest between 6 to 12 months of life during the transition from foetal to adult haemoglobin production, when gamma-chain production ceases and beta-chains fail to form.
• Present with pallor, abdominal distension secondary to hepatosplenomegaly, fatigue, and poor feeding.
• Bony abnormalities may also be present such as frontal and parietal bossing and chipmunk facies due to increased extramedullary haematopoiesis.

Beta thalassaemia intermedia

• Both beta chains affected but variable quantity and function of beta chains.
• Range of signs e.g. pallor, jaundice, splenomegaly. Can present as a less severe phenotype, as some adult haemoglobin (HbA – α2β2) is produced.
• For some, blood transfusions are only required later in life in 30s or 40s, however, each case is unique.

Beta thalassaemia minor (beta thalassaemia trait)

• Only one beta chain affected
• Heterozygous carrier
• Asymptomatic or mild anaemia that is often mistaken as iron deficiency due to microcytosis.