Thalassaemias

Question 1

Define thalassaemia?

Answer 1

Heterogenous group of recessively inherited (genetic), haematological disorders characterised by abnormal alpha/beta globin chains produced during haemoglobin synthesis

Question 2

In which 3 ethnicities is thalassaemia most prevalent?

Answer 2

Asian, african, mediterranean ancestry

Question 3

What are the 2 ways of classifying thalassaemia?

Answer 3

Severity

Which type of globin chain is abnormal

Question 4

How is is decided whether thalassaemia should be classified as alpha or beta thalassaemia?

Answer 4

Alpha-thalassaemia: Abnormal alpha-globin produced during Hb synthesis

Beta-thalassaemia: Abnormal beta-globin produced during Hb synthesis

Question 5

What is meant by the classification Thalassaemia major (homozygous)?

Answer 5

Very few or no normal globin chains, which causes severe complications

Question 6

Why is thalasaemia major also called transfusion-dependent thalassaemia?

Answer 6

Patient dependent on lifelong Packed Red Blood Cell (PRBC) transfusions (transfusion-dependent thalassaemia) every 3-4 weeks

Question 7

How often will a patient with thalassaemia major require a PRBC transfusion and why?

Answer 7

Every 3-4 weeks

To maintain Hb level above 100g/L to suppress erythropoiesis

Question 8

Why might a patient with thalassaemia undergo a splenectomy?

Answer 8

To reduce transfusion-dependence

Question 9

Why might a patient with thalassaemia take iron-chelator drugs?

Answer 9

Erythropoiesis suppression and constant transfusion increases risk of iron overload

Question 10

What is the only curative method for thalassaemia major, and what are the 2 indications?

Answer 10

Allogeneic bone marrow stem cell transplantation

Severe disease and before onset of end-organ failure

Question 11

What mutations cause beta thalassemia major (Cooley’s anaemia)?

Answer 11

2 missing/defective beta genes

Question 12

What is the typical onset age for beta thalassaemia major?

Answer 12

First 2 years of life (infancy)

Question 13

What is the typical initial clinical feature of beta thalassaemia major, and at what age does it present?

Answer 13

Severe anaemia in 3-6 months old

Question 14

What are the 2 common presentations of beta thalassaemia major?

Answer 14

Hepato-speglomegaly (liver and spleen swell)

Bone marrow expansion, which causes skull and long bones to deform

Question 15

How is beta thalassaemia major detected in newborns, and what is the management?

Answer 15

Newborn screening programme to detect disorder

Positive newborns will receive transfusions to prevent symptom manifestation

Question 16

What mutation causes alpha thalassaemia major (hydrops foetalis)?

Answer 16

Deletion of all 4 alpha genes

Question 17

Why does alpha thalassaemia major (hydrops foetalis) cause foetal death?

Answer 17

Foetal Hb (HbF) needs alpha-globin to develop into HbA (adult Hb)

But there is no alpha globin as all 4 genes are deleted

Question 18

What are the 4 common symptoms of alpha thalassaemia major?

Answer 18

Thickened placenta

Large amounts of amniotic fluid

Foetal heart enlarges

Foetal hepato-splenomegaly

Question 19

Define thalassaemia intermedia and describe its complications?

Answer 19

Clinical presentation between thalassaemia major and minor/trait, but complications are usually more typical of major

Question 20

What mutation causes alpha-thalassaemia intermedia (Hb H disease)?

Answer 20

Deletion of 3 alpha genes and association of 4 beta-globin chains

Question 21

Is alpha thalassaemia intermedia transfusion dependent or independent?

Answer 21

Variable presentation, so can be transfusion dependent or independent

Question 22

What is meant by thalassaemia minor (trait) (heterozygous)?

Answer 22

Reduced normal globin chains, so Hb level is low normal (mild microcytic anaemia) which causes patient to present as asymptomatic

Question 23

What anaemia typically presents in thalassaemia minor?

Answer 23

Mild microcytic anaemia

Question 24

In thalassaemia minor, do patients typically present as symptomatic or asymptomatic?

Answer 24

Asymptomatic

Question 25

Is thalassaemia minor transfusion dependent or independent?

Answer 25

Transfusion-independent thalassaemia

Question 26

Why is important to identify and provide genetic counselling for patients with thalassaemia minor?

Answer 26

2 people with trait can procreate with 25% chance of child inheriting thalassaemia major

Question 27

Why is it important to identify thalassaemia minor as the cause of anaemia?

Answer 27

People can undergo unnecessary treatment if mistaken for IDA

eg. given iron supplements

Question 28

What mutation causes beta thalassaemia trait?

Answer 28

One normal beta gene out of the 2 genes

Question 29

Compare the presentation of alpha and beta thalassaemia trait?

Answer 29

Very similar but more severe anaemia

Question 30

What are the classifications of severity for thalassaemia?

Answer 30

Thalassaemia major (homozygous)

Thalassaemia intermedia

Thalassaemia minor (trait) (heterozygous)