Beta thalassemia

Question 1

define:

Answer 1

• A group of genetic disorders characterised by reduced globin chain synthesis
• There is under or no production of one globin chain

Question 2

Aetiology/risk factors:

Answer 2

•	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 of alpha thalassemia:

Answer 3

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 of beta thalassemia:

Answer 4

• Beta Thalassemia Major (homozygous beta thalassemia)  little or no beta-chain synthesis
• Beta Thalassemia Intermedia - mild defect in beta-chain synthesis due to a variety of causes, e.g. co-inheritance of beta thalassemia trait with another haemoglobinopathy like HbC, 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

Symptoms of beta thalassemia major:

Answer 6

o	Severe anaemia 
o	Presenting at 3-6 months
•	This is when the change from HbF to HbA takes place 
•	Failure to thrive 
•	Prone to infection

Question 7

Symptoms of beta or alpha thalassemia trait:

Answer 7

o May be ASYMPTOMATIC

o Detected during routine blood tests or due to family history

Question 8

Signs of beta thalassemia major:

Answer 8

o Pallor
o Malaise
o Dyspnoea
o Mild jaundice
o Extramedullary haematopoiesis occurs in response to anaemia causing frontal bossing and hepatosplenomegaly
o Thalassaemia facies (facial features caused by marrow hyperplasia)

o	Hepatosplenomegaly (due to erythrocyte pooling and extramedullary haematopoiesis)
o	Osteopenia 
o	Patients with beta-thalassemia intermedia may also have these signs

Question 9

Investigations:

Answer 9

o FBC (Low Hb , Low MCV (microcytic anaemia), Low MCH

Blood Film

Bone Marrow
o Hypercellular
o Erythroid hyperplasia

Genetic Testing (rarely used)

Skull X-Ray
o ‘Hair on end’ appearance in beta thalassemia major

Question 10

What is present on the blood film:

Answer 10

o	Hypochromic microcytic anaemia 
o	Target cells – alpha thalassemia
o	Howell jolly bodies
o	Nucleated red cells 
o	High reticulocyte count
•	Hb Electrophoresis
o	Absent or reduced HbA 
o	High HbF