Thalassaemia

Question 1

Genetic disorder: thalassaemia

Answer 1

Failure to synthesize certain globin chains

Question 2

Sickle cell anaemia

Answer 2

Structural variants of Haemoglobin (Hb)

Question 3

List third disorder of haemoglobin synthesis

Answer 3

Failure to switch from fetal Hb to adult Hb

Question 4

Chromosome 16

Answer 4

Two genes for alpha-globin

Question 5

Chromosome 11

Answer 5

One gene each for beta-globin, gamma-globin and delta-globin

Question 6

Variation of fetal Hb

Answer 6

HbF = alpha2 gamma 2

Question 7

Variation of adult Hb

Answer 7

• HbA = alpha2 beta2

- HbA2 = alpha2 delta2

Question 8

Beta-thalassaemia

Answer 8

Reduced production of beta-globin chains

Question 9

beta-thalassaemia is usually caused by?

Answer 9

• Usually caused by single base mutation

Question 10

Beta-thalassaemia inheritance

Answer 10

Autosomal recessive inheritance

Question 11

Beta-thalassaemia mutation can result in?

Answer 11

Reduced beta-globin or absent beta-globin

Question 12

Beta-thalassaemia major

Answer 12

Two knock-out genes

Question 13

Heterozygote carrier for beta-thalassaemia trait

Answer 13

one knock-out gene and one normal gene

Question 14

List two effects of beta-thalassaemia

Answer 14

• HbF increases - no beta globin to replace gamma globin

- Excess alpha globin precipitate - no beta globin to pair with

Question 15

HbF increases in beta-thalassaemia

Answer 15

Leads to high oxygen affinity of RBC -> tissue hypoxia since oxygen can’t dissociate

Question 16

Excess alpha globin precipitate

Answer 16

leads to destruction of RBC precursors and haemolysis -> anaemia

Question 17

Beta thalassaemia major clinical signs

Answer 17

• Iron accumulation
• Hepatomegaly and splenomegaly
• Bone deformation

Question 18

Beta thalassaemia major haematological phenotype

Answer 18

• Hypochromic microcytic anaemia
• Anisopoikilocytosis (abnormal shape and size)
• Target and tear-drop cells
• Absent HbA
• Present HbA2
• Rise in HbF

Question 19

List the beta thalassaemia traits

Answer 19

• Asymptomatic carrier
• Normal Hb
• Hypochromic microcytosis
• Raised HbA2

Question 20

Alpha-thalassaemia definition

Answer 20

Reduced production of alpha-globin chains

Question 21

Alpha-thalassaemia is usually genetically caused by

Answer 21

Full gene deletions

Question 22

‘Normal’ variation of alpha-thalassaemia

Answer 22

4 normal genes

Question 23

alpha+ trait of alpha-thalassaemia

Answer 23

3 normal genes

Question 24

Homozygous alpha+ trait of alpha-thalassaemia

Answer 24

1 normal gene, 1 deleted gene on each chromosome (2 gene deletions)

Question 25

alpha0 trait of alpha-thalassaemia

Answer 25

2 normal genes on one chromosome, 2 deleted genes on other

Question 26

HbH disease variation of alpha-thalassaemia

Answer 26

1 normal gene

Question 27

Hydrops fetalis variation of alpha-thalassaemia

Answer 27

0 normal genes

Question 28

Variation in alpha trait of alpha thalassaemia affects ________ but presents similarly

Answer 28

inheritance pattern

Question 29

Alpha-thalassaemia results in excess?

Answer 29

Excess beta and gamma chains forming precipitants: - HbH bodies = beta4 - Hb Barts = gamma4

Question 30

HbH bodies precipitants form?

Answer 30

Beta4

Question 31

Hb Barts precipitant forms?

Answer 31

Gamma4

Question 32

Pathophysiology of alpha-thalassaemia

Answer 32

- Defect haemoglobin synthesis - Peripheral haemolysis - High oxygen affinity of HbH and Hb barts

Question 33

Peripheral haemolysis causes?

Answer 33

HbH is unstable and shortens lifespan

Question 34

High oxygen affinity of HbH and Hb barts does?

Answer 34

Does NOT give up oxygen to tissue

Question 35

Alpha-thalassaemia is clinically

Answer 35

Clinically asymptomatic

Question 36

Two gene deletions in alpha-thalassaemia

Answer 36

- Mild hypochromic microcytosis anaemia - No raise in HbA2 - Possible Hb Barts and HbH bodies

Question 37

One gene deletion in alpha-thalassaemia

Answer 37

- Normal Hb - Very mild reduction in MCV - Rarely Hb Barts

Question 38

Hb H Disease (3 gene deletions) leads to?

Answer 38

- Anaemia - HbH formation - Splenomegaly - Bone changes

Question 39

Hb Barts Hydrops Fetalis can lead to?

Answer 39

- Death in utero - Hb Barts formation - Massive hepatosplenomegaly