Beta thalassemia

Question 1

What happens in thalassemia?

Answer 1

reduced production and synthesis of one or more globin chains

Question 2

Which haemoglobin is affected with beta thalassemia?

Answer 2

HbA is not formed

HbA2 is significantly higher in a beta thal patient and HbF may also be high

Question 3

What age does beta thalassemia manifest?

Answer 3

At a young age as this is when HbF is switched off (3-6months)

Question 4

What are the different mutations that can occur in beta thal? Which are the heteozygous beta thal/beta trait?

Answer 4

B+B
B0B

One reduced OR one absent AND one normal

Question 5

What are the homozygous beta thal mutations?

Answer 5

B+B+, B0B0

but this could be the same mutation twice, or 2 different mutations both resulting in reduced synthesis of beta chain

Question 6

What are the types of mutations which can occur in beta thal?

Answer 6

Point mutations mainly which affect the promoter region/mRNA splice sites/size of the transcript leading to instability
Deletion mutation of entire gene or LCR
mutations which arise in other variant chains such as HbE and HbLepore(delta beta fusion)

Question 7

Which transcription factors are important to enhance transcription of the genes?

Answer 7

GATA1 FOG1 NF-E2 EKLF and delta and gamma to enhance trasncription of delta and gamma
(Banks 2006)

Question 8

What are the 3 types of beta thalassaemia?

Answer 8

B thal major - transfusion dependent
B thal minor - asymptomatic except under physiological stress condition only
B thal intermedia - middle severity between major and minor, not completely transfusion dependent

Question 9

What is compound heterozygosity?

Answer 9

When there are 2 abnormal mutations which both contribute to disease but they are different
e.g. compound heterozygosity for Beta+ and B0

Question 10

What is beta thal trait characterised by?

Answer 10

Unbalanced chain synthesis
Normal/near normal Hb
Low MCV and MCH
Increased red cell count
Increased % HbA2
Increased percentage of HbF

Question 11

What is the test calle which measures HbA2%?

Answer 11

HPLC

Question 12

What does beta thal trait look like on a blood film?

Answer 12

Hypochromic
Increased pallor
Microcytic
Poikilocyte

Question 13

How is beta thal trait diagnosed?

Answer 13

Increased HbA2%

Question 14

Aside from complications arising from beta thal trait, what else can cause complications?

Answer 14

Interactions of beta thal with HbS and giving sickle cell disease
Interaction with HbE which can give rise to thal intermedia or thal major

Question 15

What is beta thal major?

Answer 15

Results from homozygous mutation or compound heterozygosity

Question 16

What causes problems in beta thal major?

Answer 16

Severe imbalance of globin chain synthesis - lack of beta chains and effect of excess alpha chains

Question 17

What anaemia is exhibited in beta thal major?

Answer 17

hypochromic microcytic anaemia

Question 18

What happens when here is excess of alpha chains?

Answer 18

They precipitate in erythroblasts which damages them, this leads to ineffective erythropoiesis and an increased drive for erythropoiesis. Erythropoiesis is hyperplastic but ineffective and this can lead to bone deformity

Question 19

Draw the 2 mechanisms of anaemia in beta thalassemia major?

Answer 19

check slides 54/55 of bain beta thal

Question 20

What are the issues with transfusion?

Answer 20

Iron overload and chelation therapy needed

Question 21

How is beta thal major diagnosed?

Answer 21

Blood count and film
x/severely reduced HbA
HbF and A2 are the major Hbs

Question 22

What is the major treatment for beta thal major?

Answer 22

Transfusion with chelation (oral or parenteral)
Hydroxycarbamide
Bone marrow transplantation

Question 23

How important is chelation therapy?

Answer 23

Survival is closely related with compliance with chelation

Question 24

What is beta thal intermedia? How does it occur?

Answer 24

In between major and minor
2 genes:
occurs when both genes are a very mild form
or if there is coexisting alpha thal which ameliorates the chain imbalance
or co-inheritance of non deletional hereditary persistence of fetal Hb
1 gene:
The gene is for vvvv sever beta thal
Coexistance of triple alpha heterozygosity or homozygosity - aggravates the imbalance