haemoglobinopathies

Question 1

what type of inheritance are disorders of haemoglobin

Answer 1

mostly autosomal recessive

Question 2

which chromosomes are the alpha and beta chromosomes located on

Answer 2

alpha - 16

beta - 11

Question 3

what are the alpha like globin genes

Answer 3

alpha 1
alpha 2
zeta = alpha like 
pseudo alpha - not functional
pseudo zeta - not functional

Question 4

what are the beta like globin genes

Answer 4

beta
delta
epsilon
gamma G 
gamma A
pseudo beta - non functional

Question 5

what are the Hbs in an embryo

Answer 5

zeta2epsilon2
zeta2gamma2
alpha2epsilon2

Question 6

what are the Hbs in a foetus

Answer 6

alpha2gamma 2

Question 7

what is the normal proportion of Hbs in an adult

Answer 7

HbA = 97.5%
HbA2 = 2.0%
HbF = 0.5%

Question 8

what are the 3 broad types of haemoglobinopathies

Answer 8

alpha and beta thalassaemia
structural variants
HPFH

Question 9

what is alpha or beta thalassaemia

Answer 9

decreased synthesis of one or more of the globin chains leading to a relative imbalance between alpha and beta chains –> homotetramers of one globin chain

Question 10

what are the common causes of alpha and beta thalassaemia

Answer 10

alpha = large deletions
beta = point mutations

Question 11

what is B+ and B0

Answer 11

B+ = some beta protein still being made, but not enough
B0 = no beta protein being made at all

Question 12

what is the outcome of the globin aggregates in thalassaemia

Answer 12

aggregate, accumulate and precipitate in RBCs causing damage –> destroyed by the spleen –> haemolytic anaemia

Question 13

what type of anaemia on blood film is haemolytic anaemia

Answer 13

microcytic

hypochromic

Question 14

what is the 4 major outcomes of untreated beta-thalassaemia

Answer 14

• anaemia
• systemic iron overload
• splenomegaly
• skeletal deformities

Question 15

what causes the skeletal deformities in thalassaemia

Answer 15

body thinks it needs to make more and more RBCs as it is breaking so much down by the spleen that it recruits other sites that normally don’t make RBC –> expansion of the marrow

Question 16

what characteristic cells do you see on blood film with beta-thalassaemia

Answer 16

• hypochromic RBCs
• microcytic RBCs
• target cells
• poikilocytotic cells
• tear drop cells
• anisocytotic

Question 17

how is thalassaemia diagnosed

Answer 17

using Hb electrophoresis and HPLC

Question 18

what is the treatment of beta-thalassaemia

Answer 18

• blood transfusion
• iron chelation therapy
• splenectomy
• hormone replacement therapy
• bone marrow transplant

Question 19

what is the difference between time of presentation of alpha and beta thalassaemia

Answer 19

alpha - can present in utero (as uses alpha globin), unlike beta which can only present after birth

Question 20

what is the genotype of someone with an alpha-thalassaemia trait (carrier)

Answer 20

a-/a- or aa/–

Question 21

which genotype for alpha thalassaemia leads to HbH disease

Answer 21

a-/–

Question 22

explain the two different outcomes of carrier genotype for alpha-thalassaemia when pregnant for the feotus

Answer 22

aa/– x aa/– can lead to –/– (hydrops foetalis)

a-/a- x a-/a- can only lead to carrier (a-/a-)

Question 23

how does sickle cell disease cause problems

Answer 23

when the cells are deoxygenated –> agglutination –> sickling –> can cause occlusion of the capillaries

Question 24

what type of anaemia results from sickle cell disease

Answer 24

severe normocytic or macrocytic haemolytic anaemia

Question 25

what is the different between a compound heterozygote and a double heterozygote

Answer 25

compound = two mutations on the same chromosome
double = two mutations, but on different chromosomes

Question 26

what is the heterozygote advantage for haemoglobinopathies

Answer 26

• carriers have some resistance to malaria

- provides selective advantage where malaria is endemic