Beta thalassemia Flashcards
(24 cards)
What happens in thalassemia?
reduced production and synthesis of one or more globin chains
Which haemoglobin is affected with beta thalassemia?
HbA is not formed
HbA2 is significantly higher in a beta thal patient and HbF may also be high
What age does beta thalassemia manifest?
At a young age as this is when HbF is switched off (3-6months)
What are the different mutations that can occur in beta thal? Which are the heteozygous beta thal/beta trait?
B+B
B0B
One reduced OR one absent AND one normal
What are the homozygous beta thal mutations?
B+B+, B0B0
but this could be the same mutation twice, or 2 different mutations both resulting in reduced synthesis of beta chain
What are the types of mutations which can occur in beta thal?
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)
Which transcription factors are important to enhance transcription of the genes?
GATA1 FOG1 NF-E2 EKLF and delta and gamma to enhance trasncription of delta and gamma
(Banks 2006)
What are the 3 types of beta thalassaemia?
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
What is compound heterozygosity?
When there are 2 abnormal mutations which both contribute to disease but they are different
e.g. compound heterozygosity for Beta+ and B0
What is beta thal trait characterised by?
Unbalanced chain synthesis Normal/near normal Hb Low MCV and MCH Increased red cell count Increased % HbA2 Increased percentage of HbF
What is the test calle which measures HbA2%?
HPLC
What does beta thal trait look like on a blood film?
Hypochromic
Increased pallor
Microcytic
Poikilocyte
How is beta thal trait diagnosed?
Increased HbA2%
Aside from complications arising from beta thal trait, what else can cause complications?
Interactions of beta thal with HbS and giving sickle cell disease
Interaction with HbE which can give rise to thal intermedia or thal major
What is beta thal major?
Results from homozygous mutation or compound heterozygosity
What causes problems in beta thal major?
Severe imbalance of globin chain synthesis - lack of beta chains and effect of excess alpha chains
What anaemia is exhibited in beta thal major?
hypochromic microcytic anaemia
What happens when here is excess of alpha chains?
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
Draw the 2 mechanisms of anaemia in beta thalassemia major?
check slides 54/55 of bain beta thal
What are the issues with transfusion?
Iron overload and chelation therapy needed
How is beta thal major diagnosed?
Blood count and film
x/severely reduced HbA
HbF and A2 are the major Hbs
What is the major treatment for beta thal major?
Transfusion with chelation (oral or parenteral)
Hydroxycarbamide
Bone marrow transplantation
How important is chelation therapy?
Survival is closely related with compliance with chelation
What is beta thal intermedia? How does it occur?
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
