Thalassaemia

Question 1

Define

Answer 1

Group of genetic disorders characterised by reduced globin chain synthesis

Question 2

Causes

Answer 2

Causes → AUTOSOMAL RECESSIVE
Genetic defects result in an imbalance of globin chain production and deposition in erythroblasts and erythrocytes causing ineffective erythropoiesis, haemolysis, anaemia and extramedullary haematopoiesis

α-thalassemia – ↓α-globin chain synthesis Chromosome has 4 α-globin genes

• 4 gene deletion: Hb Barts (c4) and intrauterine death (hydrops fetalis)
• 3 gene deletion: microcytic hypochromic anaemia with splenomegaly
• 1-2 gene deletion: microcytic hypochromic red cells with no anaemia

β-thalassemia – caused by point mutations in β-globin genes on chromosome 11, leading to ↓β chain production (β+) or its absence (β0)
Various combinations of mutations are possible (e.g. β0/β0, β+/β+ or β0/β+)

• β-thalassemia major (homozygous) – both genes are abnormal, presents in 1st year with severe anaemia and failure to thrive
• β-thalassemia intermedia – mild defect in β chain synthesis causing microcytic anaemia, ↓α-chain synthesis or ↑γ chains
• β-thalassemia trait (heterogeneous carrier β0/β+) – asymptomatic, mild microcytic anaemia, ↑RCC

Question 3

Epidemiology

Answer 3

worldwide more common in Mediterranean and areas of the Middle East

Question 4

Symptoms

Answer 4

β-thalassemia major→ anaemia presenting at 3–6 months (when c-chain synthesis switches to b-chain synthesis)
Plus failure to thrive, prone to infections

Thalassaemia trait → may be asymptomatic
Detected on routine blood tests or from a family history

Question 5

Signs

Answer 5

Beta Thalassemia Major

• Pallor
• Malaise
• Dyspnoea
• Mild jaundice
• Frontal bossing
• Thalassaemia facies (facial features caused by marrow hyperplasia)
• Hepatosplenomegaly (due to erythrocyte pooling and extramedullary haematopoiesis)
• Patients with beta-thalassemia intermedia may also have these signs

Question 6

Investigations

Answer 6

Bloods

• FBC
• Low Hb
• Low MCV (microcytic anaemia)
• Low MCH

Blood Film

• Hypochromic microcytic anaemia
• Target cells
• Nucleated red cells
• High reticulocyte count

Hb Electrophoresis

• Absent or reduced HbA
• High HbF

Bone Marrow

• Hypercellular
• Erythroid hyperplasia

Genetic Testing (rarely used)

Skull X-Ray

• ‘Hair on end’ appearance in beta thalassemia major
• This is caused by expansion of marrow into the cortex