Haemaglobinopathies

Question 1

disorders of haemoglobin usually inherited as?

Answer 1

autosomal recessive

Question 2

adult haemoglobin made up of 3 things:

Answer 2

2 a chains
2 B-chains
4 iron

Question 3

normal adult haemoglobin protein is what kind of protein?

Answer 3

heterotetramer: 2:2 a:B

Question 4

a-chain found on which chromosome?

Answer 4

16

Question 5

B-chains found on which chromosome?

Answer 5

11

Question 6

where are the y-chains found? what purpose?

Answer 6

1. found on chromosome 11 with B-chains

2. part of fetal haemoglobin

Question 7

fetal haemoglobin tetrameter consists of? adult?

Answer 7

fetal: a2y2
adult: a2B2

Question 8

what happens in a or B thalassaemias?

Answer 8

decreased synthesis of one or more globins = imbalance

Question 9

structural variants of haemoglobin means what? eg.?

Answer 9

different shape, not different rate of synthesis

eg. sickle cell disease

Question 10

what is hereditary persistance of fetal haemoglobin?

Answer 10

benign condition, more fetal haemoglobin as adult

Question 11

what is HbE?

Answer 11

mild thalassaemia phenotype

Question 12

in thalassaemias, what are the haemoglobin proteins structure like?

Answer 12

homotetramers = imbalance

Question 13

how to homotetramers cause pathology?

Answer 13

insoluble in RBCs, non-functional, accumulate and damage RBCs = haemolytic anaemia

Question 14

a-thalassaemias cause usually?

Answer 14

large deletions

Question 15

B-thalassaemias cause usually?

Answer 15

point mutations
-promotor
RNA splicing
nonsense
frameshift

Question 16

what is B+ and Bo conditions:

Answer 16

B+ =some haemoglobin made

Bo = no haemoglobin whatsoever

Question 17

what do RBCs look like in B-thalassaemia homozygous?

Answer 17

microcytic

hypochromomic

Question 18

what happens to iron in B-thalassaemia

Answer 18

systemic iron overload

Question 19

consequences of bone marrow not being able to supply RBC demands?

Answer 19

marrow expansion and extramedullary erythropoiesis

Question 20

what happens to spleen in B-thalassaemia?

Answer 20

splenomegaly from filtering out the defective RBCs and the extramedullary erythropoieseis

Question 21

why are there tear-drop shaped cells in B-thalassaemia?

Answer 21

a4 aggregate inclusions on one side of cell

Question 22

what kind of cells in B-thalassaemia on slide?

Answer 22

teardrop
microcytic
hypochromic
target cells
anisocytotic

Question 23

changes to blood parameter for heterozygous B-thalassaemia?

Answer 23

minor decreased/elevations, asymptomatic

Question 24

problem with blood transfusions in B-thalassaemia?

Answer 24

exaccerbate the iron overload, need chelation

Question 25

only known cure for B-thalassaemia?

Answer 25

bone marrow transplant

Question 26

why HRT for B-thalassaemia?

Answer 26

girls get menopause at 15 due to iron complications

Question 27

with alpha-thalassaemia, what kind of homotetramers can you get?

Answer 27

y4 | B4

Question 28

how many functional genes in alpha-thalassaemia trait? two kinds?

Answer 28

2 a-/a- aa/--

Question 29

in alpha-thalassaemia trait, what do we have to worry about for parents wanting to have children?

Answer 29

If parents both have aa/-- then risk of having HbBart (--/--) is 1 in 4

Question 30

if both parents with alpha-thalassaemia trait have a-/a- then what are their children?

Answer 30

a-/a- and you get mild anaemia

Question 31

sickle cell disease point mutation where:

Answer 31

glutamate >> valine

Question 32

how does sickle cell damage RBCs?

Answer 32

in deoxygenated/stress states, the HbS aggregate and cause sickling of RBCs, repetitive leads to irreversible sickling and adhere to endothelium

Question 33

sickle cells appear how on slide?

Answer 33

severe normocytic or macrocytic

Question 34

what kind of anaemia in sickle cell?

Answer 34

haemolytic anaemia

Question 35

how is MCV/MCH affected in heterozygous vs. homozygous sickle cell?

Answer 35

heterozygous: normal or reduced homozygous: normal unless in crises

Question 36

what are compound heterozygotes?

Answer 36

2 kinds of mutation on the B-globin mutation, HbS or HbE?

Question 37

what are double heterozygotes?

Answer 37

B and a globin mutation. (actually do better, less imbalance)

Question 38

future therapies of thalassaemias?

Answer 38

gene therapy