Condition- Thalassaemia

Question 1

Describe the inheritance of Thalassaemia

Answer 1

Autosomal Recessive

Question 2

Describe the epidemiology of thalassaemia

Answer 2

Common in Mediterranean

Also seen in Arab and S.Asia and Africa

Question 3

Alpha thalassaemia is caused by a mutation on which Chromosome?

Answer 3

Chr 16

Question 4

How many alpha genes does an individual have?

Answer 4

4

Question 5

List the different stages of alpha thalassaemia depending on the number of gene deletions and state how they clinically manifest

Answer 5

• 1 gene deletion = a⁺ (asymptomatic- blood film shows microcytic hypochromic anaemia)
• 2 gene deletions = a⁰ ​(asymptomatic- blood film shows microcytic hypochromic anaemia)
• 3 gene deletions = HbH (anaemia, hepatosplenomegally and bone enlargement)
• 4 gene deletions = HbBarts Hydrops Fetalis (intrauterine death)

Question 6

Beta Thalassaemia is caused by a mutation on which chromosome?

Answer 6

Chr 11

Question 7

How many beta genes does an individual have?

Answer 7

2

Question 8

State the different stages of Beta Thalassaemia and describe the clinical manifestation of each

Answer 8

• B⁰B⁰ = Beta Thalassaemia Major (severe anaemia, hepatosplenomegaly, bone growth, jaundice)
• B⁺B⁺ = Beta Thalassaemia Intermedia
• B⁺B or B⁰B = Beta Thalassaemia Minor/ trait (asymptomatic- may have mild anaemia)

Question 9

At what age do symptoms of Beta Thalassaemia manifest? and why?

Answer 9

3-6 months

This is when Gamma globin production is switched off and Beta globin starts being formed (the switch between HbF and HbA)

Question 10

List some of the signs and symptoms of Beta Thalassaemia Major.

(can categorise them into symtpoms of anaemia, extra-medullary haematopoiesis, hamolyisis)

Answer 10

• Symptoms of anaemia- SOB, fatigue, failure the thrive, pallor
• Symtpoms of extra-medullary haematopoiesis
  
  • Hepatosplenomegaly- recurrent infections
  • Bone enlargement= frontal bossing, chipmunk fascies
• Symptoms of haemolysis
  
  • High Bilirubin => jaundice
  • High Haem => haemochromatosis- arrhythmias, pericarditis, cirrhosis, DM, hypothyroid

Question 11

What causes this symptom of thalassaemia?

Answer 11

‘Chipmunk fascies’ = Extramedullary haemopoiesis in the skull

Question 12

What would you see on an FBC of somenone with thalassaemia?

Answer 12

Low Hb, Low MCV, Low MCH

Question 13

What would you see on a blood film of someone with Thalassaemia?

Answer 13

• Microcytic, hypochromic RBCs
• Target cells (because theres extra surface membrane compared to haemoglobin)
• High reticulocytes
• Nucleated RBCs and Howard Jolly Bodies

Question 14

What test would you conduct to confirm the diagnosis of Beta Thalassaemia and what would be the positive result?

Answer 14

Hb Electrophoresis

• Low/absent HbA
• High HbF and HbA2 (delta and gamma globulins take over)

Question 15

Which alpha thalassaemias can be picked up on Hb electrophoresis?

Answer 15

HbH and HbBarts

Question 16

State a common finding of Beta Thalassaemia on a skull xray

Answer 16

‘Hair on end’ appearance