Thalassaemia

Question 1

what is thalassaemia?

Answer 1

A haemoglobinopathy of the thalassaemia type meaning reduced or absent globin chains

Question 2

what is alpha thalassaemia?

Answer 2

A thalassaemia leading to reduced/absent production of the alpha globin chains

Question 3

what is beta thalassaemia?

Answer 3

A thalassaemia leading to reduced/absent production of the beta globin chains

Question 4

what are the denotations used in thalassaemia?

Answer 4

(0)- absent production of the chain due to a mutation

(+)- reduced production due to a mutation.

Question 5

what genes do we normally have for haemoglobin production?

Answer 5

4 alpha globin genes

2 beta globin genes

Question 6

what is the inheritance pattern of thalassaemia?

Answer 6

autosomal recessive

Question 7

what mutation most commonly leads to alpha thalassaemia?

Answer 7

Deletions- but a huge variety of mutations can cause alpha thalassaemia.

Question 8

what are the types of alpha thalassaemia?

Answer 8

1. Alpha thalassaemia minima (aa/a-)
2. Alpha thalassaemia trait (a-/a-)
3. Haemoglobin H disease (a-/–)
4. Bart’s syndrome (–/–)

Question 9

what are the symptoms of alpha thalassaemia minima (aa/a-)?

Answer 9

Asymptomatic often have normal MCV.

Question 10

what is the management of alpha thalassaemia minima (aa/a-)?

Answer 10

No management needed.

Question 11

what are the features of alpha thalassaemia trait (a-/a-)(aa/–)?

Answer 11

Asymptomatic or mild microcytic anaemia with a mild reduction in MCV.

Question 12

what is the management of alpha thalassaemia trait (a-/a-)(aa/–)?

Answer 12

Often none needed

Question 13

what is the condition where they have three abnormal alpha genes and one normal alpha genes?

Answer 13

Haemoglobin H disease

Question 14

what are features of haemoglobin H disease (a-/–)?

Answer 14

Reduced red cell survival with a hypochromic microcytic anaemia

• pallor, anaemia, jaundice, hepatosplenomegaly, aplastic crisis and leg ulcers.

Question 15

what are the key treatment options for haemoglobin H disease?

Answer 15

transfusions
iron chelation therapy with deferasirox if they get overload
folic acid supplements
splenectomy

Question 16

what is haemoglobin barts disease (–/–)?

Answer 16

inheritance of four abnormal alpha genes which is incompatible with extrauterine life

Question 17

why is barts disease often presenting in the first 6 months of life?

Answer 17

In Bart’s disease there are no alpha globin chains and these are needed for both HbA (normal Hb) and HbF (foetal haemoglobin).

Question 18

what can babies develop in barts disease?

Answer 18

severe anaemia, high output cardiac faliure and oedema= hydrops fetalis.

Question 19

what haemoglobin types are absent in barts disease?

Answer 19

No alpha chains due to all abnormal alpha genes. This leads to no HbA2, HbF and HbA.

Question 20

what is the management of barts disease?

Answer 20

intrauterine transfusions, bone marrow transplants.

Question 21

what is the only way to diagnose alpha thalassaemia minima or trait?

Answer 21

Genetic sequencing

Question 22

how is alpha thalassaemia diagnosed?

Answer 22

Haemoglobin analysis with electrophoresis

Question 23

what antenatal screening is in place for alpha thalassaemia?

Answer 23

Family origin questionnaire to determine further testing by week 10 gestation

Question 24

what the investigation results in alpha thalassaemia?

Answer 24

FBC: low Hb, low MCV (Have microcytic anaemia)
Blood film: microcytic and hypochromic RBC’s

LFT’s: raised unconjugated bilirubinaemia (can cause pigmented gallstones and jaundice)

Haemolysis screen: raised lactate dehydrogenase, low haptoglobin.
Direct antiglobulin test (negative, non immune haemolysis)

Question 25

what is beta thalassaemia?

Answer 25

Reduced or absent production of the beta globin chain

Question 26

how many copies of the beta globin gene do we normally have?

Answer 26

2

Question 27

what are the main forms of beta thalassaemia?

Answer 27

1. beta thalassaemia minor/trait (b+/b or b0/b)
2. beta thalassaemia intermedia (b+/b+)
3. beta thalassaemia major (b+/b0 or b0/b0)