Thalassaemia

Question 1

What is thalassaemia?

Answer 1

A blood condition which causes alteration of haemoglobin structure.
Two types: alpha and beta

Question 2

Where is alpha-thalassaemia more common?

Answer 2

Mediterranean countries
Africa
The Middle East
India
Central Asia

Question 3

What is the inheritance of alpha-thalassaemia

Answer 3

Complex: 2 alpha-globin alleles are inherited from each parent. The amount of missing alleles and the combination of HBA1 and HBA2 genes affected will determine the precise risk of inheriting alpha-thalassaemia

Question 4

What are the variations of alpha-thalassaemia?

Answer 4

1 gene defect - asymptomatic silent carrier
2 gene defects - alpha-thalassaemia minor (minor anaemia)
3 gene defects - haemoglobin H disease (severe anaemia)
4 gene defects - haemoglobin Bart’s Hydrops Fetalis (fatal)

Question 5

What is HBA1?

Answer 5

A gene which provides instructions for the production of alpha-globin.

Question 6

What is alpha-globin?

Answer 6

A subunit of haemoglobin.

Question 7

What is Haemoglobin A?

Answer 7

A type of haemoglobin making up ~97% of all haemoglobin in the body.
Consists of two alpha-globins and two beta-globins

Question 8

What is Haemoglobin A2?

Answer 8

A type of haemoglobin making up ~3% of all haemoglobin in the body.
Made up of two alpha-globins and two delta-globins

Question 9

What is HBA2?

Answer 9

Gene which produces alpha-globins

Question 10

What is the cytogenetic location of the mutation for alpha-thalassaemia?

Answer 10

16p13.3

Question 11

What is beta-thalassaemia?

Answer 11

Blood disorder involving a point mutation in the HBB gene in chromosome

Question 12

What is alpha-thalassaemia>

Answer 12

Blood disorder involving the deletion of the HBA1 and HBA2 genes in chromosome 16

Question 13

What is the location of the point mutation for beta-thalassaemia?

Answer 13

11p15.4

Question 14

Where is beta-thalassaemia more common?

Answer 14

Mediterranean countries
North Africa
The Middle East
India
Central Asia
South-East Asia

Question 15

What is the inheritance for beta-thalassaemia?

Answer 15

Autosomal recessive

Question 16

What are the variations of beta-thalassaemia?

Answer 16

(HHB↓ = decreased beta-chain synthesis, HBBX = no beta-chain synthesis)

HBB + HBB = wild type; healthy
HBB↓ + HBBX = beta thalassaemia minor
HBB↓ + HBB↓ = beta thalassaemia intermedia
HBBX + HBBX = beta thalassaemia major

Question 17

How is thalassaemia diagnosed? When does diagnosis usually occur?

Answer 17

Full blood test

• measures haemoglobin
• measures different kinds of blood cells

Haemoglobin test
- measures different kinds of haemoglobin present

Genetic screening

Diagnosis usually occurs in first 6 months of life. Can be fatal in early childhood without treatment.

Question 18

What is the treatment for thalassaemia?

Answer 18

No cure.

Management involves regular blood transfusions

• boosts haemoglobin levels
• • can lead to buildup in iron levels, side effects including diabetes, heart failure and liver disease
• iron chelates are used to reduce iron levels
• • bind with iron and allow it to be removed by the kidneys

Question 19

What is the effect of thalassaemia on the gene pool?

Answer 19

More mutations in red blood cell formation increase the severity of the disease

• mild thalassaemia = 1-2 mutations
• severe thalassaemia = 3-4 mutations

More mutations in the gene pool increases the mortality rate

Resistance to malaria increases allele frequency