Haemoglobinopathies and Thalassaemias​

Question 1

Hb A

Answer 1

normal adult haemoglobin
2 𝜶 chains and 2 β chains
96% in adult blood

Question 2

Hb A2

Answer 2

2 α chains, 2 δ chains​
2-3% in adult blood

Question 3

Hb F

Answer 3

Foetal haemoglobin
2 𝜶 chains and 2 γ(gamma) chains more affinity for O2 binding
<1% in adult blood

Question 4

what is the haemoglobin composition in adult blood?

Answer 4

96% Hb A, 3% Hb A2 and 1% Hb F​

Question 5

Haemoglobinopathy

Answer 5

A mutation in the globin genes that give rise to different types and amounts of haemoglobin​

Question 6

what are the 2 types of Haemoglobinopathy

Answer 6

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​

Question 7

Hb S

Answer 7

Sickle Cell Anaemia​
2 𝜶 chains and 2 β chains

Question 8

Sickle Cell Anaemia​

Answer 8

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​

Question 9

Heterozygous Trait sickle cell (Hb A + Hb S)​

Question 10

Homozygous Trait (Hb S + Hb S)​

Question 11

4 types of sickle cell crises​

Question 12

sickle solubility test

Question 13

Hb S+ prognosis

Question 14

Hb S+ Treatment

Question 15

Hb C

Question 16

where is α thalassaemia​ most common?

Question 17

where is β thalassaemia​ most common?

Question 18

α+ Homozygote ​

Answer 18

(α-/α-)
mutation on each allele

Question 19

αo Heterozygote

Answer 19

(αα/–) ​
two mutations on one allele

Question 20

Haemoglobin H Disease
(thalassaemia intermedia​)

Answer 20

(–/α-) ​

Hb approx 80 g/l
Hb H + 4 beta chains

Question 21

Haemoglobin Barts Hydrops Foetalis ​

Answer 21

(–/–)​
- no alpha inheritance

most severe form

Question 22

The major abnormal form of hemoglobin that accumulates in a fetus with the severe form of a-thalassemia (hydrops fetalis) is composed of:

Answer 22

A tetramer of 4 g-subunits (g4)
only gamma chains

Question 23

describe the inheritance of sickle cell anaemia

Answer 23

always caused by the same point mutation in the beta-globin gene: an A->T transversion
substitution of valine (hydrophobic) for glutamate (hydrophilic)

Question 24

how is b-thalassemia major (B0/B0) treated?

Answer 24

transfusions
increasing b globin production
decreasing a globin production
iron chelation therapy

Question 25

why would increasing a globin production in a patient with b thalassaemia major be a bad thing?

Answer 25

exacerbate homotetramer formation and worsen the patient’s condition.
– more of the bad Hb made

Question 26

why may Severe b-thalassemia be asymptomatic in a baby until several months old?

Answer 26

The g (gamma) to b-globin switch is not complete until several months after birth

Question 27

what is a b0 allele?

Answer 27

mutation where no b-globin is produced

Question 28

HbH disease is rarely observed in offspring of African American couples because:

Answer 28

he predominant chromosome associated with a-thalassemia in African Americans is (a-)

Question 29

Hb H disease (a-/–)

Answer 29

allele (–) is common to southeast Asia, rarely in African Americans