Thalassaemia

Question 1

What are the normal chains in a haemoglobin molecule?

Answer 1

2 alpha chains and 2 beta chains

Question 2

What are haemoglobinopatheis?

Answer 2

Inherited conditions resulting in a relative lack of normal globin chains due to absent genes or a variant globin chain

Question 3

What does the severity of haemoglobinopathies depend on?

Answer 3

• Amount of abnormal haemoglobin
• Type of abnormal haemoglobin
• Ameliorating factors

Question 4

What does the severity of haemoglobinopathies depend on?

Answer 4

• Amount of abnormal haemoglobin
• Type of abnormal haemoglobin
• Ameliorating factors

Question 5

Describe the genetics of Hb production

Answer 5

• Globin chains are produced on ribosomes

* control of production is mainly at the transcription level and depends on the availability of haem

Question 6

What happens if there is a problem with one of the alpha chain genes?

Answer 6

There are problems in utero, resulting in miscarriage early on in the pregnancy

Question 7

What happens if there are problems with the beta genes?

Answer 7

They will experience problems in early childhood

Question 8

Describe the haemoglobin chains from conception to childhood

Answer 8

•At conception:
- Gower 1: theta and epsilon chains
- Gower 2: alpha and epsilon
- Portland 1: theta and gamma
•Then produce Hb F: Alpha and gamma
•Then Hb A (majority after 3 months post partum): alpha and beta
•Small amount of Hb A2 produced just before birth and remains at less than 5% of Hb: alpha and delta

Question 9

What is thalassaemia?

Answer 9

Relative lack of globin genes

Question 10

What globin genes are we meant to have?

Answer 10

• 4 alpha globin genes on 2 Ch16

* 2 beta globin genes of 2 Ch 11

Question 11

State the alpha gene permutations from least harmful to most harmful

Answer 11

• lacking on alpha gene: α+ thalassaemia trait
• Lacking 2 alpha genes, one on each chromosome: homozygous α+ thalassaemia trait
• Lacking 2 alpha genes on one chromosome: αo thalassaemia trait
• Lakcing 3 alpha genes: HbH disease
• No alpha genes: Alpha thalassaemia major

Question 12

Describe the clinical significance of α+ thalassaemia trait

Answer 12

Will not be anaemic but may have mild microcytosis

Question 13

Describe the clinical significance of homozygous α+/ αo thalassaemia trait

Answer 13

Microcytosis, increased red cell count and sometimes a very mild asymptomatic anaemia

Question 14

Describe the clinical aspect of HbH disease

Answer 14

Significant anaemia (Hb approx 75g/l) and abnormal shaped small red blood cells

Question 15

Describe the clinical significance of alpha thalassaemia major

Answer 15

not compatible with life as need alpha chains for foetal haemoglobin

Question 16

Explain the pathogenesis of HbH disease

Answer 16

Because of the lack of alpha genes there is an excess of beta chains that join together

Question 17

Describe the treatment of HbH disease

Answer 17

• Asymptomatic most of the time but may need treatment during periods of stress e.g. post op or pregnancy
• Blood transfusion

Question 18

What is beta thalassaemia major?

Answer 18

• Autosomal recessive disorder
• Missing both beta genes
• Unable to make HbA (adult haemoglobin) resulting in significant dyserythropoiesis (abnormal red cells)

Question 19

Describe a blood film in beta thalassaemia major

Answer 19

• Many different shapes
• Hypochromic
• microcytic cells

Question 20

Describe a blood film in beta thalassaemia major

Answer 20

• Many different shapes
• Hypochromic
• microcytic cells

Question 21

What may you see on a head x ray of someone with beta thalassaemia major?

Answer 21

Hair on end appearance due to bone changes

Question 22

Describe the clinical management of beta thalassaemia major

Answer 22

• Transfusion dependent from a young age - first couple of years: 2-3 units every 3 weeks (consider venous port)
• Why it is also called transfusion dependent thalassaemia
• Due to transfusions will have iron overload - iron chelation and monitor organs affected by iron overload (heart, liver, endocrine, thyroid etc.)
• Consider bone marrow transplantation in childhood if sibling match