Haemoglobinopathies

Question 1

describe the structure of Hb

Answer 1

a tetramer made of two alpha globin chains and two beta globin chains, with one haem group attached to each globin

Question 2

describe the structure of haem

Answer 2

a porphyrin ring with an iron at the centre

Question 3

what causes the development of haemoglobinopathies?

Answer 3

problems with the globin chains

Question 4

what is HbA?

Answer 4

adult haemoglobin

two alpha and two beta chains

Question 5

what is HbA2?

Answer 5

2 alpha chains and 2 delta chains

a functional but rare form of Hb

Question 6

what is HbF?

Answer 6

fetal haemoglobin

two alpha and two gamma chains

Question 7

where are the genes for alpha globin chains found and how many are there per cell?

Answer 7

chromosome 16

two per chromosome = four per cell

Question 8

where are the genes for beta globin chains found and how many are there per cell?

Answer 8

chromosome 11

one per chromosome = two per cell

Question 9

when are levels of adult hemoglobin reached and what implication does this have for globin problems?

Answer 9

6-12 months of age

means problems with the beta chain wont manifest til this time, as beta globin is only found in HbA

Question 10

what are haemoglobinopathies?

Answer 10

hereditary conditions affecting globin chain synthesis

Question 11

what is the inheritance pattern seen in haemoglobinopathies?

Answer 11

autosomal recessive

Question 12

what are the two main groups of haemoglobinopathies?

Answer 12

thalassaemia

structure Hb variants

Question 13

what infection has been associated with increased rates of haemoglobinopathies in certain areas?

Answer 13

malaria

Question 14

what are the two types of thalassaemia?

Answer 14

alpha thalassaemia

beta thalassaemia

Question 15

what type of anaemia is seen in thalassaemia and why?

Answer 15

inadequate Hb production causes a microcytic hypochromic anaemia

Question 16

what causes alpha thalassaemia?

Answer 16

mutations affecting alpha globin chain synthesis

Question 17

what genotype is seen in individuals unaffected by alpha thalassaemia?

Answer 17

four normal alpha genes = (aa/aa)

Question 18

what types of haemoglobin can be affected by alpha thalassaemia?

Answer 18

all as they all contain alpha globin (HbA, HbA2 and HbF)

Question 19

what are the three types of alpha thalassaemia?

Answer 19

alpha thalassaemia trait
HbH disease
Hb Bart’s hydrops fetalis

Question 20

what is the genotype of someone with alpha thalassaemia trait?

Answer 20

one or two alpha genes missing i.e. (-a/aa) or (–/aa)

Question 21

how does alpha thalassaemia trait present?

Answer 21

asymptomatic carrier state

microcytic hypochromic red cells with normal ferritin

Question 22

what genotype is seen in people with HbH disease?

Answer 22

only one alpha gene left (–/-a)

Question 23

how does HbH disease present?

Answer 23

moderate to severe anaemia with very low MCV and MCH

Question 24

what is a+ thalassaemia?

Answer 24

one alpha gene deleted from a chromosome (-a/aa)

Question 25

what is a0 thalassamia?

Answer 25

both alpha genes deleted from a chromosome (--/aa)

Question 26

why is HbH disease called that?

Answer 26

excess beta globin chains form tetramers

Question 27

in which area is there a higher prevalence of HbH disease?

Answer 27

south east asia

Question 28

what is the genotype seen in Hb Bart's?

Answer 28

no functional alpha genes (--/--)

Question 29

how does Hb Bart's usually present?

Answer 29

intrauterine death as not compatible with life

Question 30

what causes beta thalassaemia?

Answer 30

point mutations in the beta globin chain resulting in disordered beta chain synthesis

Question 31

what type of Hb is affected by beta thalassaemia?

Answer 31

only HbA as this is the only type that contains beta chains

Question 32

what does B+ mean?

Answer 32

reduced beta chain production

Question 33

what does B0 mean?

Answer 33

absent beta chain production

Question 34

what are the three types of beta thalassaemia?

Answer 34

beta thalassaemia trait beta thalassaemia intermedia beta thalassaemia major

Question 35

what genotypes can be seen in beta thalassaemia trait?

Answer 35

B+/B or B0/B

Question 36

how does beta thalassaemia trait present?

Answer 36

asymptomatic may have a mild anaemia low MCV/MCH

Question 37

what is diagnostic of beta thalassaemia trait?

Answer 37

raised HbA2 levels

Question 38

what genotypes can be seen in beta thalassaemia intermedia?

Answer 38

B+/B+ or B0/B+

Question 39

what do patients with beta thalassaemia intermedia need?

Answer 39

occasional transfusions

Question 40

what genotype is seen in beta thalassaemia major?

Answer 40

B0/B0

Question 41

what do patients with beta thalassaemia major need?

Answer 41

lifelong transfusions

Question 42

when does beta thalassaemia major present and why?

Answer 42

6-24 months old as HbF falls

Question 43

how does beta thalassaemia major present?

Answer 43

pallor | failure to thrive

Question 44

what is the Hb target in beta thalassaemia major?

Answer 44

95-105

Question 45

what is a possible management option for beta thalassaemia major if done early?

Answer 45

bone marrow transplant

Question 46

what three systems can be impacted by iron overload?

Answer 46

endocrine cardiac liver

Question 47

what effects can iron overload have on the endocrine system?

Answer 47

impaired growth + development diabetes osteoporosis

Question 48

what effects can iron overload have on the heart?

Answer 48

cardiomyopathy | arrythmias

Question 49

what effects can iron overload have on liver disease?

Answer 49

cirrhosis | HCC

Question 50

how should iron overload be managed in an anaemic patient?

Answer 50

iron chelating drugs

Question 51

name an iron chelating drug

Answer 51

desferrioxamine

Question 52

what causes sickling disorders?

Answer 52

point mutation in codon 6 of the beta globin chain, producing Bs alters the structure of Hb

Question 53

what type of Hb is seen in sickling disorders?

Answer 53

HbS

Question 54

what are the three types of sickling disorders?

Answer 54

sickle cell trait sickle cell anaemia sickle cell disease

Question 55

what haemoglobin is seen in sickle cell trait?

Answer 55

HbAS majority is HbA

Question 56

what genotype is seen in sickle cell trait?

Answer 56

B/Bs (one normal one abnormal)

Question 57

how does sickle cell trait present?

Answer 57

asymptomatic carrier state may sickle in severe hypoxia

Question 58

describe the appearance of the blood film in sickle cell trait

Answer 58

normal

Question 59

what haemoglobin is seen in sickle cell anaemia?

Answer 59

HbSS

Question 60

what genotype is seen in sickle cell anaemia?

Answer 60

Bs/Bs two abnormal B genes

Question 61

how does sickle cell anaemia present?

Answer 61

episodes of sickle crisis causing severe pain

Question 62

what causes sickle crisis?

Answer 62

altered shape of RBCs resulting in vascular occlusion and tissue infarction

Question 63

what happens to the RBC lifespan in sickle cell anaemia?

Answer 63

reduced due to chronic haemolysis

Question 64

where are sickled RBCs removed in sickle cell anaemia and what effect can this have?

Answer 64

liver and spleen hyposplenism

Question 65

name some possible precipitants of sickle crisis

Answer 65

hypoxia dehydration infection stress

Question 66

how is sickle crisis managed?

Answer 66

opiate analgesia hydration rest oxygen

Question 67

what needs to be given to patients with sickle cell anaemia due to hyposplenism?

Answer 67

prophylactic penicillin | regular immunisations

Question 68

what is sickle cell disease?

Answer 68

when patients have compound heterozygosity for HbS and another B chain mutation

Question 69

what investigations can be used to diagnose haemoglobinopathies?

Answer 69

HPLC | electrophoresis (less common)