Haemoglobin E and C, Beta thalassemia and interactions

Question 1

What is the pathophysiology of HbE?

Answer 1

There are false splice sites so defective mRNA is produced

this results in a reduced rate of synthesis of Be and therefore total beta globin chain

Question 2

What does HbE with Bthal look like?

Answer 2

Asymptomatic or of Bthal major/intermedia

Question 3

What does HbE homozygosity look like on the blood film?

Answer 3

hypochromic microcytic anaemia - this is usually mild

Question 4

With what does HbE travel with in electrophoresis on cellulose gel?

Answer 4

Travels the same as C and A2

Only way to tell the difference is to use DNA analysis

Question 5

With what does HbE travel with in electrophoresis on cellulose gel(alkaline)?

Answer 5

Travels the same as C

Only way to tell the difference is to use DNA analysis

Question 6

What is the molecular basis of HbE?

Answer 6

Mutation chainging glutamic acid to lysine leads to abnormal splice site and reduced mRNA production.
Can lead to loss of mRNA due to early stop codon

Question 7

What does HbE travel with on acid electrophoresis?

Answer 7

A

Question 8

What happens with the HLPC for HbE?

Answer 8

Lies in the same as A2 band

so if A2 rises to 25-30% suspect HbE

Question 9

What are the complications seen in HbE/Bthal?

Answer 9

Growth failure
Hypersplenism
Leg ulcers
Gallstones
DM
Cirrhosis

Question 10

Describe HbLepore

Answer 10

Encoded by delta beta fusion gene

Question 11

Describe the genetic basis for HbLepore

Answer 11

There is unequal cross over between delta and beta genes during meiosis

Question 12

Why is HbLepore not thalassemic?

Answer 12

You have a functional beta gene, only one chain is affected

Question 13

What does heterozygous HbLepore look like? And homozygous?

Answer 13

Heterozygous, beta thal trait

Homozygous - b thal intermedia

Question 14

What is the mutation in HbC?

Answer 14

There is single point mutation from guanine to lysine in codon 6

Question 15

Why does sickle cell disease occur in SC individuals but not AS ones?

Answer 15

HbS and HbA don’t interact, only sever hypoxia causes sickling in AS
HbC also binds to the band 3 kcl co transporter and dehydrates cell, increasing the sickling

Question 16

Why is there an increased clinical picture in HbSC

Answer 16

reduced o2 affinity>Increase of Hb than in SS> increased thrombotic risk with avascular necrosis and proliferative retinopathy

Question 17

Why may SC be better than SCD

Answer 17

Less haemolysis as rbcs last longer so less aplastic crises fewer gallstones
Less sickling - less tissue infarction - less painful crises
THis means that splenic atrophy is delayed leading to fewer infections

Question 18

What is HbO arab?

Answer 18

Another variant common in the middle east, leads to activation of the gardos channel and dehydration of the cell causing sickling

Question 19

What is seen on the blood film of HbC cells?

Answer 19

HbC crystals - empty red cells where the Hb is like a crystal
they have hard edges