Alpha-thalassaemia

Question 1

What is alpha thalassaemia and how does it arise?

Answer 1

• A quantitative haemoglobinopathy. It is present globally but is prevalent in the Mediterranean, Middle East.
• Presents as autosomal recessive.
• Presents at 6 months, when HbF levels drop.
• It is due to alpha gene deletions (chromosome 16), and the number of deletions determines the severity of disease. This leads to defective HbF and HbA.
• The lack of alpha chains leads to the production of excess gamma chains which form tetramers - HB Bart, and also excess B chains which form HbH.

Question 2

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

Answer 2

• The number of deletions determines severity of disease. We have 2 copies of chromosome 16, each with 2 genes so 2 defective genes are required for disease
• Silent carrier: heterozygous alpha thalassaemia 2, one gene deletion.
• Thalassaemia minor: homozygous alpha thalassaemia 2 or heterozygous alpha thalassaemia 1, 2 gene deletions.
• HbH disease: alpha thalassaemia 1 or 2, 3 gene deletions.
• Bart’s hydrops fetalis: homozygous alpha thalassaemia 1, 4 gene deletions.

Question 3

What are the symptoms and their explanations?

Answer 3

• Carriers are asymptomatic.
• Minor show anaemia - this is due to the increased removal of RBCs.
• HbH show chronic haemolytic anaemia - this is due to increased removal of RBCs by the RES.
• Barts hydrops fetalis show a shortened lifespan - this is due to this type being lethal and incompatible with life. These neonates have oedema, heart and lung problems, severe anaemia, hepatosplenomegaly and cognitive development issues.
• Hepatosplenomegaly - this is due to increased RES removal of RBCs.
• Pallor and jaundice - due to increased bilirubin.

Question 4

What are the laboratory findings?

Answer 4

• Minor: microcytic hypochromic anaemia.

- HbH: hypochromic, microcytic cells, target cells, different shapes and sizes of RBCs. Inclusion bodies.

Question 5

What further tests should be carried out to confirm diagnosis?

Answer 5

• HPLC and Hb electrophoresis: this will show increased beta and gamma chains in HbH. No alpha chains/genes will be seen with Bart’s hydrops fetalis.

Question 6

How is alpha thalassaemia treated?

Answer 6

• Occasional blood transfusions for mild cases.

- For severe cases, regular transfusions, splenectomy and iron chelation.