Family with Thalassaemia Tutorial Flashcards
What is the difference between genetic diseases of haemoglobinopathies
vs thalassaemia
Haemoglobinopathies are due to a mutation in haemoglobin genes, causing abnormal poorly functioning globin chains whereas Thalassaemia is due to mutations that cause insufficient production and therefore amount of normal protein of one of the globin chains- alpha or beta.
What is the basic structure of Haemoglobin (Hb) and what are the 3 different types
Hb is a heterotetramer of 2 different globin chains, each chain carrying haeme group with Fe to allow binding and unbinding of oxygen.
There is HbA (maj)= 2a, 2b
HbA2= 2a, 2sigma
HbF(oetal) = 2a, 2 gamma
How is thalassaemia inherited- alpha and what are the main treatments of the disease for anaemia caused by this disease
Thalassaemia is autosomal recessive inheritance, with heterozygotes having minor disease compared to homozygotes.
Treatments involve blood transfusion, bone marrow transplant with chelation therapy to treat iron overload- can cause early death
How are haemoglobinopathies inherited
Autosomal co-dominant so both traits/pathologies in a heterozygote are expressed.
What is the initial step for finding testing to be parents for thalassaemia
Undertake screening tests of blood count, blood film review or haemoglobinopathy screen to find if parents have underlying thalassaemia and the nature of thalassaemia trait
What does MCV stand for in a blood count
Mean cell volume - average size of rbcs in blood indicating micro or macrocytosis.
Can characterise a type of anaemia
What is HbH
haemoglobin made of 4 b chains where there is significant a globin chain reduction
How is abnormal Hb protein detected - screen for haemoglobinopathy or thalassaemia
Using Hb electrophoresis on the different Hb protein forms found in the sample against known samples
If anaemia is not present, does this exclude a mild thalassaemia trait or haemoglobinopathy?
no, should still do a haemoglobinopathy screen because heterozygotes can still have normal haemoglobins
What needs to be known before prenatal diagnostic testing
The specific mutations in the globin chain gene affected. For some hbinopathies this is one known mutation, but for thalassaemia the DNA has to be screened for common mutations in that ethnic group.
What types of testing can be done on samples to determine presence of mutations
PCR, altered restriction enzyme recognition site or DNA sequencing.
Give an example of coupound heterozygosity in the haemoglobin gene
Someone who carries the recessive allele for a haemoglobinopathy and thalassaemia.
