Beta-thalassaemia

Question 1

What is beta-thalassaemia and how does it arise?

Answer 1

• A quantitative haemoglobinopathy due to a reduced synthesis of the normal beta globin chain. It is present globally but is prevalent in the Mediterranean, Middle East.
• It is due to a point mutation on the beta globin gene (chromosome 11) that result in a reduced or absent synthesis of beta globin chains. This then causes an increase in alpha and gamma globin chains, leading to HbF.
• These point mutations can be in the gene or in a nearby promoter or enhancer region.
• They can lead to nonsense mutations, frameshift mutations, stop codons, splicing, cause insertions or deletions, or point mutations (most common).

Question 2

What determines the severity of disease and what are the different classifications?

Answer 2

• The number of abnormal genes present determines severity of disease.
• B-thalassaemia minor: silent carrier, has one normal B globin gene and one which produces a reduced level of beta globin.
• B-thalassaemia trait: disease trait, has one normal B globin gene and one which produces no beta globin.
• B-thalassaemia intermedia: intermediate disease, has 2 copies which produce a reduced level of beta globin.
• B-thalassaemia major: severe disease, has 2 copies which produce no beta globin.

Question 3

What are the symptoms and their explanations?

Answer 3

• Severe anaemia - this is due to unstable RBCs which are removed by RES macrophages.
• Hepatosplenomegaly - this is due to increased RES macrophage action.
• Bone marrow hyperplasia and a bossed skull (expansion of the skull) - this is due to constitutive erythropoiesis.
• Growth retardation and poor musculature - due to impaired RBCs not delivering enough oxygen to tissues.
• Pallor and jaundice - due to increased bilirubin.
• Painful leg ulcers.
• Iron overload - due to repeated blood transfusions.

Question 4

What are the laboratory findings?

Answer 4

• There are various findings due to the heterogenous nature.
• Microcytic, hypochromic anaemia.
• High numbers of reticulocytes.
• Blood film shows a variety of cells:
• Bite cells.
• Elongated/oval cells.
• Mis-shaped cells.
• With supravital staining, Heinz bodies are seen. This is due to the unstable excess alpha chains (as a result of no beta chains to pair with) precipitating out as Heinz bodies.
• Nucleated WBCs.
• Microcytic and hypochromic RBCs.

Question 5

What further tests should be carried out to confirm diagnosis?

Answer 5

• HPLC - HbF will be high. In B-thalassaemia minor, HbA2 will be raised.
• Hb electrophoresis - HbA will be reduced, and almost all circulating Hb will HbF.

Question 6

How is B-thalassaemia major treated?

Answer 6

• Regular transfusions.
• Folic acid.
• Iron chelation.
• Splenectomy or partial splenectomy.
• Endocrine therapy: growth hormone.
• Immunisation against hepatitis.
• Allogenic stem cell transplant.

Question 7

How is B-thalassaemia minor and intermedia treated?

Answer 7

• Regular blood transfusions.
• Folic acid.
• Iron chelation.