Thalassaemia

Question 1

Definition

Answer 1

A group of genetic disorders characterised by reduced globin chain synthesis

Question 2

Aetiology

Answer 2

• Autosomal recessive
• Result in an imbalance of globin chain production and deposition in erythroblasts and erythrocytes

• This leads to:
o Ineffective erythropoiesis 
o Haemolysis
o Anaemia
o Extramedullary haematopoiesis

Question 3

Types (alpha)

Answer 3

o ALPHA THALASSEMIA - reduction in alpha-globin chain synthesis. There are
FOUR alpha-globin genes on the chromosome.

• 4 gene deletion = Haemoglobin Barts Hydrops Fetalis (intrauterine death)
• 3 gene deletion = Haemoglobin H –> microcytic hypochromic anaemia and
splenomegaly
• 2 gene deletion = Alpha 0 thalassemia –> microcytic hypochromic red cells, NO ANAEMIA
• 1 gene deletion = Alpha+ thalassemia –> microcytic hypochromic red cells, NO ANAEMIA

Question 4

Types (beta)

Answer 4

o BETA THALASSEMIA

• Beta Thalassemia Major (homozygous beta thalassemia) –> little or no
beta-chain synthesis

• Beta Thalassemia Intermedia - mild defect in beta-chain synthesis leads to:
▪ Microcytic anaemia
▪ Reduced alpha-chain synthesis
▪ Increased gamma-chain synthesis

• Beta Thalassemia Trait (heterozygous carrier state)
▪ ASYMPTOMATIC
▪ Mild microcytic anaemia
▪ Increased red cell count

Question 5

Epidemiology

Answer 5

• WORLDWIDE

* Most common in the MEDITERRANEAN and areas of the Middle-East

Question 6

Presenting symptoms

Answer 6

• Beta Thalassemia Major
o Anaemia
o Presenting at 3-6 months
• This is when the change from HbF to HbA takes place
• Failure to thrive
• Prone to infection

• Alpha or Beta Thalassemia Trait
o May be ASYMPTOMATIC
o Detected during routine blood tests or due to family history

Question 7

Signs on physical examination

Answer 7

Beta Thalassemia Major

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

Question 8

Investigations (bloods)

Answer 8

o FBC

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

Question 9

Investigations (blood film)

Answer 9

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

Question 10

Investigations (other)

Answer 10

• Hb Electrophoresis
o Absent or reduced HbA
o High HbF

• Bone Marrow
o Hypercellular
o Erythroid hyperplasia

• Genetic Testing (rarely used)

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