Thalassaemias

Question 1

What is Thalsseamia ?

Answer 1

• autosomal recessive inherited disorders
• characterised by the decreased/absent synthesis of either alpha or beta polypeptide chain of haemoglobin

Question 2

How many clinical forms are there of alpha-Thalasaemia ?

Answer 2

• 4
• typically arise from gene deletion
• in normal state humans have 4 copies of alpha gene -> gene from each parent on chromosomes 16

Question 3

Describe 4 gene deletions

Answer 3

• incompatible with life
• results in death in utero - Hydrops Fetalis

Question 4

Describe 3-Alpha gene deletion

Answer 4

• results in moderately severe anaemia
• marked by the presence of haemoglobin H (B4)
  -pateints develop splenomegaly & hepatosplenomegaly

Question 5

Describe Hb Constant Springs

Answer 5

• Hb constant sprin-point mutation in the stop codon of the alpha chain
• this adds on extra 31 amino acids at the C-terminal end
• low production rates of a-chain

Question 6

What are the 3 classifications of B Thalassemia ?

Answer 6

• B thal minor/trait
• B thal intermediate
• B thal major

Question 7

What can cause B-Thalaseamia?

Answer 7

1. Gene deletion - indian origin- removal of 600 pairs from the 3’ end of the B-globin gene
2. transcriptional mutations
3. splicing
4. Non-functional RNA

Question 8

How can Thalassaemia be diagnosed ?

Answer 8

• haemolytic anaemia
• MCV <70 fl
• normal ferritin

Question 9

What is GAP-PCR ?

Answer 9

• based upon the inability of PCR primers complementary to DNA sequences that are far apart to direct amplification unless a deletion brings them closer together

Question 10

What is MLPA?

Answer 10

• Multiplex ligation - dependent probe amplification
• simple & able to detect major deletions in the a - b globin gene

Question 11

How can thalassaemia be prevented ?

Answer 11

• genetic counselling -> carriers of aa estimate risk of Hydrops Fetalis or Haemoglobin H disease
• Antenatal screening programmes

Question 12

How can Thalassaemia be treated ?

Answer 12

• asymptomatic carries –> iron supplementation only in cases of iron deficiency
• thalassaemia intermedia -> blood transfusions in cases of growth impariment & skeletal deformities

Question 13

How can Thalassaemia Major be treated ?

Answer 13

• regular hypertransfusion - to maintain Hb > 95g/L
• iron chelation to prevent iron overload
• mutlidiscplinary approach- specialised nursing, cardiologist, genetic counsellor

Question 14

What could be a potential cure of Thalassaemia?

Answer 14

• haematopoietic stem cell transplant - depends on HLA match