Haemoglobinopathies Flashcards
How many Haem groups are there per globin chain?
1 per globin chain => 4 per Hb molecule (each can pick up one O2)
What are the major forms of Hb?
HbA (α2β2 ), HbA2 (α2δ2) HbF (α2γ2)
What chromosomes control globin chain production?
Alpha genes (aa,aa) chromosome 16, Beta genes (bb) chromosome 11
When does adult haemoglobin (HbA) production take over from foetal haemoglobin (HbF)?
6-12 months of age
How are haemoglobinopathies genetically inherited?
autosomal recessive
What are the two main groups of haemoglobinopathies?
Thalassaemias (less globin chain synthesis), Structural haemoglobin variants (normal production but chain abnormal)
What globin chains can be affected in a thalassemia?
Alpha thalassaemia (α chains), Beta thalassaemia (β chains)
What are the possible consequences of a thalassemia?
Accumulation of globin chains (toxic to cell), Haemolysis, Ineffective erythropoiesis
Where in the world are thalassemias most prevalent?
Africa and Asia
What are the different types of alpha thalassemia (based on the number of working genes)?
Unaffected = 4 normal α genes (αα/αα)
TRAIT = one or two alpha genes missing
HbH = only one alpha gene left (–/-α )
Hb Barts hydrops fetalis = NO functional α genes (–/–)
Patients with alpha thalassemia trait will be asymptomatic. TRUE/FALSE?
TRUE
- no treatment req’d
HOw do RBCs appear on a blood film of a patient with an alpha thalassemia trait? What is this similar to, and how are the two distinguished?
Microcytic, hypochromic red cells with mild anaemia
Similar to iron deficiency
=> but FERRITIN NORMAL
Describe the blood results of a patient with HbH disease?
Anaemia with very low MCV and MCH
How is HbH formed in HbH disease?
Excess β chains form tetramers (β4)
as no alpha chains to bind to
Where is HbH disease (and alpha thalassemias in general) most common?
South East Asia
HOw may patients with HbH disease present, and what treatment may they require?
Jaundice and splenomegaly
Patients may need transfusion
What is Hb Barts Hydrops Foetalis?
- Severest form of α thalassaemia
- Minimal or no α chain production
=> HbF and HbA can’t be made - Instead tetramers of Hb Barts (γ4) and HbH (β4) produced
Where in the world is there a higher risk of Hb Barts Hydrops Foetalis?
Risk if both parents from SE Asia
- as this is where α0 (–) thalassemia trait prevalent
How is the risk of Hb Barts Hydrops Foetalis minimised?
Antenatal screening
Babies who are born with Hydrops Foetalis have what distinct clinical features?
- Profound anaemia
- Cardiac failure
- Growth retardation
- Severe hepatosplenomegaly
- Skeletal and cardiovascular abnormalities
- HOWEVER Almost all die in utero**
What type of Hb production is affected in beta thalassemias?
HbA (α2β2) affected
=> as only β chains depleted
What are the different classifications of beta thalassemia?
β thalassaemia trait
- Asymptomatic
- No/mild anaemia
- Low MCV/MCH
- Raised HbA2 diagnostic
β thalassaemia intermedia
- Moderate severity
- requires occasional transfusion
β thalassaemia major (β0/β0)
- Severe
- Lifelong transfusions
When does Beta thalassemia major usually present?
Presents aged 6-24 months (as HbF falls)
What Hb is found in beta thalassemia major?
Mainly HbF
No HbA
