Thalassaemia (zero to finals)

Question 1

What is thalassaemia?

Answer 1

An inherited blood disorder caused by a genetic defect in the protein chains that make up haemoglobin.

Question 2

Normal haemoglobin consists of what chain types?

Answer 2

2 alpha chains and 2 beta chains

Question 3

Defects in alpha-globin chains lead to alpha thalassaemia. True/false?

Answer 3

True

Defects in alpha-globin chains lead to alpha thalassaemia.

Defects in the beta-globin chains lead to beta thalassaemia.

Both conditions are autosomal recessive.

The overall effect is varying degrees of anaemia, depending on the type and mutation.

Question 4

How can thalassaemia develop into haemolytic anaemia and how does this affect the spleen?

Answer 4

In patients with thalassaemia, the red blood cells are more fragile and break down easily, causing haemolytic anaemia.

The spleen acts as a sieve, filtering the blood and removing older cells. The spleen collects all the destroyed red blood cells, resulting in splenomegaly.

Question 5

What are the features of thalassaemia?

Answer 5

Features are dependant on the type however the universal features are:

Microcytic anaemia (low mean corpuscular volume)
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development

Question 6

Investigations for thalassaemia?

Answer 6

Microcytic anaemia (low mean cell volume) is a typical finding on a full blood count.

Raised ferritin suggests iron overload.

Haemoglobin electrophoresis is used to diagnose globin abnormalities.

DNA testing can be used to look for the genetic abnormality.

All pregnant women in the UK are offered a screening test for thalassaemia at booking.

Question 7

When may iron overload occur in thalassaemia?

Answer 7

Increased iron absorption in the gastrointestinal tract

Blood transfusions

Question 8

Iron overload in thalassaemia can result in what symptoms and complications?

Answer 8

Liver cirrhosis

Hypogonadism

Hypothyroidism

Heart failure

Diabetes

Osteoporosis

Question 9

What causes alpha thalassaemia?

Answer 9

Defects in the alpha-globin chain

Question 10

What chromosome hold the genes that code for alpha globin?

Answer 10

Chromosome 16

Question 11

Management of alpha thalassaemia?

Answer 11

Monitoring

Blood transfusions

Splenectomy may be performed

Bone marrow transplant can be curative

Question 12

What is HbH disease?

Answer 12

More severe form of alpha thalassaemia

Only one working α gene per cell (–/-α )

Anaemia with very low MCV (microcytic) and MCH

MCH = a measurement of the average amount of hemoglobin in each red blood cell.

Question 13

Can there be a variation in symptoms for alpha thalassaemia?

Answer 13

Yes

The severity of symptoms varies depending on the type and number of genetic defects, ranging from entirely asymptomatic as a carrier, to moderate anaemia (haemoglobin H disease), to intrauterine death due to severe foetal anaemia (alpha thalassemia major).

Question 14

What causes beta thalassaemia?

Answer 14

Defects in the beta-globin chain

Question 15

What chromosome hold the genes that code for beta globin?

Answer 15

Chromosome 11

Question 16

Do the beta-globin gene defects only consist of deletions?

Answer 16

No, the gene defects can either consist of abnormal copies that retain some function or deletion genes with no function in the beta-globin.

Question 17

How many types of beta thalassaemia are there?

Answer 17

3 types

Question 18

What are the 3 types of beta thalassaemia?

Answer 18

Thalassaemia minor

Thalassaemia intermedia

Thalassaemia major

Question 19

What is thalassaemia minor?

Answer 19

Patients with beta thalassaemia minor (also called thalassaemia trait) are carriers of an abnormally functioning beta-globin gene.

They have one abnormal and one normal gene.

Question 20

Can thalassemia minor cause microcytic anaemia and does it require treatment?

Answer 20

Thalassaemia minor causes mild microcytic anaemia and usually only requires monitoring.

Question 21

What is thalassaemia intermedia?

Answer 21

Patients with beta thalassaemia intermedia have two abnormal copies of the beta-globin gene.

This can be either:

Two defective genes
One defective gene and one deletion gene

Question 22

What can thalassaemia intermedia cause and what is the management for thalassaemia intermedia?

Answer 22

Thalassaemia intermedia causes more significant microcytic anaemia.

Patients require monitoring and may need occasional blood transfusions. They may require iron chelation to prevent iron overload.

Question 23

What is thalassaemia major?

Answer 23

Patients with beta thalassaemia major are homozygous for the deletion genes.

They have no functioning beta-globin genes. This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood.

Question 24

What effect does thalassaemia major have on the bone marrow and how does it increase fracture risk?

Answer 24

The bone marrow is under so much strain to produce extra red blood cells to compensate for the chronic anaemia that it expands enough to increase the risk of fractures and change the patient’s appearance.

Question 25

What are some of the abnormal features relating to bone changes due to thalassaemia major?

Answer 25

Abnormal features relating to bone changes include:

Frontal bossing (prominent forehead)
Enlarged maxilla (prominent cheekbones)
Depressed nasal bridge (flat nose)
Protruding upper teeth

Question 26

Management for thalassaemia major?

Answer 26

Management involves regular transfusions, iron chelation (removal of excess iron from body) and splenectomy.

A bone marrow transplant can be curative.