Haemoglobinopathies Flashcards
What is alpha-thalassaemia?
Alpha-thalassaemia is due to a deficiency of alpha chains in haemoglobin.
Where are the alpha-globulin genes located?
2 separate alpha-globulin genes are located on each chromosome 16.
How does clinical severity of alpha-thalassaemia depend on the number of affected alleles?
If 1 or 2 alpha globulin alleles are affected, the blood picture would be hypochromic and microcytic, but the Hb level would be typically normal.
What happens if 3 alpha globulin alleles are affected?
If 3 alpha globulin alleles are affected, it results in a hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease.
What is the outcome if all 4 alpha globulin alleles are affected?
If all 4 alpha globulin alleles are affected (i.e. homozygote), then it results in death in utero (hydrops fetalis, Bart’s hydrops).
What is Beta-thalassaemia major?
Absence of beta globulin chains on chromosome 11.
When does Beta-thalassaemia major typically present?
In the first year of life with failure to thrive and hepatosplenomegaly.
What type of anaemia is associated with Beta-thalassaemia major?
Microcytic anaemia.
What are the hemoglobin levels in Beta-thalassaemia major?
HbA2 and HbF are raised; HbA is absent.
What is the management for Beta-thalassaemia major?
Repeated transfusion leads to iron overload and organ failure.
Why is iron chelation therapy important in Beta-thalassaemia major?
To manage iron overload due to repeated transfusions.
Example of iron chelation therapy: desferrioxamine.
What are thalassaemias?
Thalassaemias are a group of genetic disorders characterised by a reduced production rate of either alpha or beta chains.
What is beta-thalassaemia trait?
Beta-thalassaemia trait is an autosomal recessive condition characterised by a mild hypochromic, microcytic anaemia.
Is beta-thalassaemia trait usually symptomatic?
It is usually asymptomatic.
What are the features of beta-thalassaemia trait?
Features include mild hypochromic, microcytic anaemia and microcytosis that is characteristically disproportionate to the anaemia.
What is the HbA2 level in beta-thalassaemia trait?
HbA2 is raised (> 3.5%).
What is sickle-cell anaemia?
Sickle-cell anaemia is an autosomal recessive condition that results from the synthesis of an abnormal haemoglobin chain termed HbS.
Who is more commonly affected by sickle-cell anaemia?
It is more common in people of African descent as the heterozygous condition offers some protection against malaria.
What percentage of UK Afro-Caribbean’s are carriers of HbS?
Around 10% of UK Afro-Caribbean’s are carriers of HbS (i.e. heterozygous).
When do symptoms in homozygotes typically develop?
Symptoms in homozygotes don’t tend to develop until 4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin.
What are the types of haemoglobin related to sickle-cell anaemia?
Normal haemoglobin: HbAA, Sickle cell trait: HbAS, Homozygous sickle cell disease: HbSS, Milder form (HbC): HbSC.
What amino acid substitution occurs in sickle-cell anaemia?
The polar amino acid glutamate is substituted by non-polar valine in each of the two beta chains (codon 6).
What is the effect of the amino acid substitution in sickle-cell anaemia?
This substitution decreases the water solubility of deoxy-Hb.
What happens to HbS molecules in the deoxygenated state?
In the deoxygenated state, the HbS molecules polymerise and cause RBCs to sickle.
