haemoglobinopathies

Question 1

where does synthesis of haem occur?

Answer 1

in normoblasts in the bone marrow

within mitochondria and cytosol

Question 2

what are the normal functioning adult haemoglobins?

Answer 2

HbA, HbA2 and HbF

Question 3

what percentage of adult haemoglobin does HbA make up? what globin chains is it made up of?

Answer 3

96% (major component)

2 alpha and 2 beta

Question 4

what percentage of adult haemoglobin does HbA2 make up? what globin chains is it made up of?

Answer 4

3% (minor component)

3 alpha and 2 delta

Question 5

what percentage of adult haemoglobin does HbF make up? what globin chains is it made up of?

Answer 5

less than 1% but it predominate haemoglobin during fetal development
2 alpha and 2 gamma

Question 6

when are embryonic Hb’s seen?

Answer 6

only in the first trimester

Question 7

what are the different kinds of haemoglobinopathies?

Answer 7

Hb variants

thalassaemias

Question 8

what are Hb variants?

Answer 8

disorders that affect the structure and quantity of haemoglobin produced

Question 9

what are thalassaemias?

Answer 9

caused by deletions in the genes that code for haemoglobin synthesis and result in reduced globin production and chain imbalance

Question 10

which globin gene is affected in thalassaemia?

Answer 10

any chain can be affected

most deletions occur in alpha and beta thalassaemia

Question 11

how can thalassaemias be detected?

Answer 11

by compensation through increased production of a different specific haemoglobin form and/or a decrease in other globin chains along with ‘thalassaemic’ red cell indices

Question 12

when do structural variants arise in thalassaemia? and how many exist?

Answer 12

when one or more amino acid is substituted for a different one
over 800 different variants exist

Question 13

which structural variant is most significant in thalassaemia?

Answer 13

sickle cell haemoglobin

Question 14

what is the structural variant causes sickle cell haemoglobin?

Answer 14

amino acid at position 6 on the beta globin chain is substituted
glutamine to valine

Question 15

are we able to detect the structural change when it is internal or external and why? what methods allow us to visualise the change?

Answer 15

external
it causes a change in the net charge
electrophoretic/chromatographic methods allow visualisation

Question 16

when does alpha thalassaemia occur?

Answer 16

when some of the alpha chain gene/s are deleted

usually inherit two genes from each parent

Question 17

what are the modes of inheritance for alpha thalassaemia?

Answer 17

alpha+ in the heterozygous form occurs when there is one gene deletion (from one parent)
alpha+ in the homozygous form occurs when there is two gene deletion (one from each parent)
alpha o in heterozygous form occurs when there are two gene deletions (2 from one parent)
HbH occurs when only one alpha gene is inherited
Hb barts is when no alpha gene is inherited. this is incompatible with life and is fatal

Question 18

what populations is alpha+ heterozygous form commonly seen?

Answer 18

in africans, afro-caribbeans, indians, pakistanis and bangladeshi

Question 19

what populations is alpha o heterozygous form commonly seen?

Answer 19

far east asians 
chinese 
greeks 
turkish 
some meditteranean and middle eastern europeans

Question 20

what are the red cell indices involved in alpha thalassaemia?

Answer 20

increased RBC 
normal Hb 
decreased MCV
decreased MCH 
normal MCHC 
if iron deficient then all cell indices are lowered

Question 21

would the chromatogram be normal for alpha thalassaemia?

Answer 21

yes
normal HbA2
no treatment required

Question 22

how many beta globin genes do we inherit from each parent?

Answer 22

one

Question 23

when does beta+ thalassaemia occur?

Answer 23

when some of the beta globin chain is deleted

Question 24

when does beta o thalassaemia occur?

Answer 24

when one beta globin gene is absent

Question 25

would the chromatogram be normal for beta thalassaemia?

Answer 25

no

raised levels of HbA2 (above 3.5%) and HbF (above 1%)

Question 26

clinical presentation of beta thalassaemia major

Answer 26

severely anaemic and ill from 6 months old

beta globin chain deleted in full

Question 27

blood film of beta thalassaemia major

Answer 27

abnormal
low Hb
microcytic features
abnormal red blood cells

Question 28

chromatogram of beta thalassaemia major

Answer 28

abnormal
no HbA seen
majority of Hb is HbF

Question 29

what is the treatment for beta thalassaemia major?

Answer 29

transfusion dependant

Question 30

what can HbS polymerise to form and what can it cause?

Answer 30

forms long crystals that can rupture cells and cause severe pain due to venous occlusion in small blood vessels