Haemaglobinopathies Flashcards
disorders of haemoglobin usually inherited as?
autosomal recessive
adult haemoglobin made up of 3 things:
2 a chains
2 B-chains
4 iron
normal adult haemoglobin protein is what kind of protein?
heterotetramer: 2:2 a:B
a-chain found on which chromosome?
16
B-chains found on which chromosome?
11
where are the y-chains found? what purpose?
- found on chromosome 11 with B-chains
2. part of fetal haemoglobin
fetal haemoglobin tetrameter consists of? adult?
fetal: a2y2
adult: a2B2
what happens in a or B thalassaemias?
decreased synthesis of one or more globins = imbalance
structural variants of haemoglobin means what? eg.?
different shape, not different rate of synthesis
eg. sickle cell disease
what is hereditary persistance of fetal haemoglobin?
benign condition, more fetal haemoglobin as adult
what is HbE?
mild thalassaemia phenotype
in thalassaemias, what are the haemoglobin proteins structure like?
homotetramers = imbalance
how to homotetramers cause pathology?
insoluble in RBCs, non-functional, accumulate and damage RBCs = haemolytic anaemia
a-thalassaemias cause usually?
large deletions
B-thalassaemias cause usually?
point mutations -promotor RNA splicing nonsense frameshift
what is B+ and Bo conditions:
B+ =some haemoglobin made
Bo = no haemoglobin whatsoever
what do RBCs look like in B-thalassaemia homozygous?
microcytic
hypochromomic
what happens to iron in B-thalassaemia
systemic iron overload
consequences of bone marrow not being able to supply RBC demands?
marrow expansion and extramedullary erythropoiesis
what happens to spleen in B-thalassaemia?
splenomegaly from filtering out the defective RBCs and the extramedullary erythropoieseis
why are there tear-drop shaped cells in B-thalassaemia?
a4 aggregate inclusions on one side of cell
what kind of cells in B-thalassaemia on slide?
teardrop microcytic hypochromic target cells anisocytotic
changes to blood parameter for heterozygous B-thalassaemia?
minor decreased/elevations, asymptomatic
problem with blood transfusions in B-thalassaemia?
exaccerbate the iron overload, need chelation
only known cure for B-thalassaemia?
bone marrow transplant
why HRT for B-thalassaemia?
girls get menopause at 15 due to iron complications
with alpha-thalassaemia, what kind of homotetramers can you get?
y4
B4
how many functional genes in alpha-thalassaemia trait? two kinds?
2
a-/a-
aa/–
in alpha-thalassaemia trait, what do we have to worry about for parents wanting to have children?
If parents both have aa/– then risk of having HbBart (–/–) is 1 in 4
if both parents with alpha-thalassaemia trait have a-/a- then what are their children?
a-/a- and you get mild anaemia
sickle cell disease point mutation where:
glutamate»_space; valine
how does sickle cell damage RBCs?
in deoxygenated/stress states, the HbS aggregate and cause sickling of RBCs, repetitive leads to irreversible sickling and adhere to endothelium
sickle cells appear how on slide?
severe normocytic or macrocytic
what kind of anaemia in sickle cell?
haemolytic anaemia
how is MCV/MCH affected in heterozygous vs. homozygous sickle cell?
heterozygous: normal or reduced
homozygous: normal unless in crises
what are compound heterozygotes?
2 kinds of mutation on the B-globin mutation, HbS or HbE?
what are double heterozygotes?
B and a globin mutation. (actually do better, less imbalance)
future therapies of thalassaemias?
gene therapy
