PBL 9 - Thalassaemia Flashcards
How does the subunit structure of normal adult haemoglobin differ from that of fetal haemoglobin? (2 marks)
Normal adult haemoglobin consists of two alpha (1/2 mark) and two beta (1/2 mark) subunits (chains) . Fetal haemoglobin consists of two alpha (1/2 mark) and two gamma subunits (1/2 mark).
What abnormality occurs specifically in alpha thalassaemia? (1 mark). What are the different degrees of this disease, and describe briefly the signs corresponding to each degree of severity. (2 marks)
In Alpha thalassaemia there is reduced synthesis (1/2 mark) of the alpha subunits of haemoglobin (1/2 mark).
There are usually four copies of the gene to produce alpha chain haemoglobin (1/2 mark). If all four copies are missing this is incompatible with life and leads to in-utero death (1/2 mark). Three copies missing leads to severe microcytic anaemia (1/2 mark). Loss of one or two genes does not normally lead to any symptoms (1/2 mark).
What is the main abnormality that would be detected in a blood test from patients with beta thalassaemia major (1 mark)
Microcytic anaemia
- What is the major form of haemoglobin in patients with beta thalassaemia major (1 mark)
Fetal Haemoglobin (HbF)
- Explain briefly why Kadeer Ahmed has a protruberant abdomen (1 mark)
There is enlargement of the liver and spleen (1/2 mark) as a result of excessive red cell destruction (1/2 mark) and extramedullary haemopoiesis (1/2 mark) (any two half marks)
Name two main forms of treatment suitable for Kadeer (2 marks)
Regular blood transfusions (1/2 mark) with iron chelation to prevent iron overload (1/2 mark)
Bone marrow transplant (1 mark)
Where is blood cell production in the fetus, newborn and adult? (3)
o Before birth:
= Mesoblastic stage - At 3rd week: Yolk sac +mesothelial layers of the placenta (HbGower1)
=Hepatic stage - At 6 weeks – Liver & Spleen (HbF)
=Myeloid stage- 3rd month onwards - the bone marrow
o After birth:
=Age up to 5 years : The bone marrow in all bones (HbA)
= Age 5 to 20-25 years : Marrow of the long bones
= Age 25+ years: marrow of the membranous bones
What is the difference between the structure of embryonic and fetal hb? (2)
Fetal Hb - HbF - A2Y2
fetal - Hb Gower 1 - Z2E2
What is the percentage of HbA, HbF and HbA2 in adult blood?
o HbA – 10% in neonates, 96-97% in adults
o HbA2 - <1% in neonates, 2-2.5% in adults
o HbF – 90% in neonates, <1% in adults
What chromosome do B thalassaemia mutations occur on? (1)
e within the gene complex
itself or in promoter or enhancer regions on chromosome 11.
What are the two genotypes of B thalassaemia ? (2)
heterozygous beta thalassaemia trait (minor) and
homozygous beta thalassaemia (thalassaemia major or intermedia).
Why are iron chelators given and give an example? (1)
E.g Desferioxamine
bind to iron in blood
Prevents the Fenton reaction occurring (hydroxyl radicals form) which can cause cirrhosis, growth retardation, heart failure, diabetes
Why might genetic counselling be necessary, what would they need to discuss? (1)
- Pregnant woman with Hb abnormality – test partner
- Both have abnormality – risk of defect in offspring
Discuss - foetus affect, termination offered
How can prenatal diagnosis of thalassaemia be done? (1)
DNA (chorionic villous or amniotic fluid) or fetal blood
Normal structure and function of haemoglobin
4 polypeptide chains with a haem group
Each haem has 1 atom of ferrous iron that combines with 4x oxygen