Haemoglobinopathies and Thalassaemias Flashcards
Hb A
normal adult haemoglobin
2 𝜶 chains and 2 β chains
96% in adult blood
Hb A2
2 α chains, 2 δ chains
2-3% in adult blood
Hb F
Foetal haemoglobin
2 𝜶 chains and 2 γ(gamma) chains more affinity for O2 binding
<1% in adult blood
what is the haemoglobin composition in adult blood?
96% Hb A, 3% Hb A2 and 1% Hb F
Haemoglobinopathy
A mutation in the globin genes that give rise to different types and amounts of haemoglobin
what are the 2 types of Haemoglobinopathy
Structural variants
- Mutation of globin gene which produces functionally abnormal haemoglobin
- Qualitative defect
Thalassaemia
- Mutation of globin gene which results in reduced or no globin chain synthesis
- Quantitative defect
Hb S
Sickle Cell Anaemia
2 𝜶 chains and 2 β chains
Sickle Cell Anaemia
Hb S
a lower ability to carry oxygen
less soluble – cannot change back shape after oxygen binding
still 2 𝜶 chains and 2 β chains
can be homozygous or heterozygous
GLU replaced by VAL
Heterozygous Trait sickle cell (Hb A + Hb S)
Homozygous Trait (Hb S + Hb S)
4 types of sickle cell crises
sickle solubility test
Hb S+ prognosis
Hb S+ Treatment
Hb C
where is α thalassaemia most common?
where is β thalassaemia most common?
α+ Homozygote
(α-/α-)
mutation on each allele
αo Heterozygote
(αα/–)
two mutations on one allele
Haemoglobin H Disease
(thalassaemia intermedia)
(–/α-)
Hb approx 80 g/l
Hb H + 4 beta chains
Haemoglobin Barts Hydrops Foetalis
(–/–)
- no alpha inheritance
most severe form
The major abnormal form of hemoglobin that accumulates in a fetus with the severe form of a-thalassemia (hydrops fetalis) is composed of:
A tetramer of 4 g-subunits (g4)
only gamma chains
describe the inheritance of sickle cell anaemia
always caused by the same point mutation in the beta-globin gene: an A->T transversion
substitution of valine (hydrophobic) for glutamate (hydrophilic)
how is b-thalassemia major (B0/B0) treated?
transfusions
increasing b globin production
decreasing a globin production
iron chelation therapy
why would increasing a globin production in a patient with b thalassaemia major be a bad thing?
exacerbate homotetramer formation and worsen the patient’s condition.
– more of the bad Hb made
why may Severe b-thalassemia be asymptomatic in a baby until several months old?
The g (gamma) to b-globin switch is not complete until several months after birth
what is a b0 allele?
mutation where no b-globin is produced
HbH disease is rarely observed in offspring of African American couples because:
he predominant chromosome associated with a-thalassemia in African Americans is (a-)
Hb H disease (a-/–)
allele (–) is common to southeast Asia, rarely in African Americans
