Haemaglobinopathies

Question 1

Name the three types of haemoglobin

Answer 1

HbA - two alpha two beta
HbA2 - two alpha two delta
HbF - two alpha two gamma

Question 2

Where are the alpha globin genes found and how many are there?

Answer 2

Chromosome 16 - two per chromosome and four per cell

Question 3

Where are the beta globulin genes found and how many are there?

Answer 3

Chromosome 11 - one per chromosome and two per cell

Question 4

When does globulin expression reach adult levels?

Answer 4

6-12 months

Question 5

Define haemoglobinopathy

Answer 5

Hereditary conditions that affect globulin chain synthesis

Question 6

What mode of inheritance do haemoglobulinopathies follow?

Answer 6

Autosomal recessive

Question 7

What disease is linked to haemoglobinopathies?

Answer 7

Malaria

Question 8

Name the two groups of haemoglobinopathies

Answer 8

Thalassaemias

Structural Hb variants

Question 9

What is thalassaemia?

Answer 9

Reduced globulin chain synthesis and Hb production

Question 10

What do thalassaemias cause?

Answer 10

Microcytic hypochromic anaemia

Question 11

Name the three variations of alpha thalassaemia

Answer 11

Trait
HbH disease
Hb Barts hydrops fetalis

Question 12

Describe alpha thalassaemia trait

Answer 12

One or two missing genes, asymptomatic carrier with microcytic hypochromic red cells but normal ferritin

Question 13

How does HbH disease arise?

Answer 13

Loss of three alpha genes
Moderate to severe anaemia
Excess beta chains form HbH

Question 14

Where is HbH disease most common?

Answer 14

SE asia due to alpha nought endemic

Question 15

How will HbH present?

Answer 15

Jaundice, severe anaemia, splenomegaly

Question 16

When may patients with HbH require a transfusion?

Answer 16

During acute illness

Question 17

What genetic issues leads to Hb Barts hydrops fetalis?

Answer 17

No functional genes - incompatible with life
Excess beta chains form HbH
Excess gamma chains form Hb Barts

Question 18

How will Hb Barts hydros fetalis present?

Answer 18

Profound anaemia, cardiac failure, hepatosplenomegaly, growth retardation, skeletal abnormalities

Question 19

What types of Hb are beta chains present?

Answer 19

HbA

Question 20

Name three beta thalamassamias

Answer 20

Trait
Intermedia
Major

Question 21

Describe beta thalassaemia trait

Answer 21

Asymptomatic, no/mild anaemia due to one abnormal copy of the gene

Question 22

What is the genetic cause of beta thalassaemia intermedia?

Answer 22

Two defective genes

One defective gene and one deletion

Question 23

How will beta thalassaemia intermedia present?

Answer 23

Moderate severity - microcytic hypochromic anaemia need regular monitoring and may need transfusion

Question 24

What is the genetic cause of beta thalassaemia major?

Answer 24

Two deletion genes

Question 25

How does beta thalassaemia major present?

Answer 25

``` Severe microcytic hypochromic anaemia Hepatosplenomegaly Skeletal deformity Failure to thrive Palor ```

Question 26

At what age does beta thalassaemia major commonly present?

Answer 26

6-24 months

Question 27

What happens to the Hb in beta thalassaemia major?

Answer 27

No HbA, mainly HbF

Question 28

Why do you see skeletal deformity in beta thalassaemia major?

Answer 28

Extramedullary haematopoiesis

Question 29

What skeletal changes are classical of beta thalassaemia major?

Answer 29

Frontal bossing | Hair on end skull x-ray

Question 30

How is beta thalassaemia major managed?

Answer 30

Regular transfusion

Question 31

What is the major risk of regular transfusion?

Answer 31

Iron overload

Question 32

What are the consequences of iron overload?

Answer 32

Endocrine dysfunction - diabetes, osteoporosis Cardiac Disease - arrhythmias, cardiomyopathy Liver Disease - cirrhosis, cancer Sepsis

Question 33

What drug can be given with transfusion to prevent overload?

Answer 33

Iron chelating drugs

Question 34

How do sickling disorders arise?

Answer 34

Point mutations in beta globulin gene cause glutamine to change to valine and produce HbS

Question 35

What happens to HbS?

Answer 35

It can polymerise if exposed to low oxygen levels for a prolonged time with distorts the red cell and damages the membrane

Question 36

What is sickle cell trait?

Answer 36

Asymptomatic carrier state, generally HbS levels are too low to have an effect

Question 37

What does sickle cell anaemia cause?

Answer 37

Episodes of tissue infarction due to microvascular occlusion

Question 38

How does sickle cell crisis present?

Answer 38

Severe pain due to ischaemia and inflammation

Question 39

What is the effect of sickle cell on the spleen?

Answer 39

Chronic haemolysis due to distorted red cells, shorter life span - sequestered in the spleen causing splenic infarcts and hyposplenism

Question 40

What can precipitate a sickle cell crisis?

Answer 40

Hypoxia, dehydration, infection, stress, fatigue

Question 41

How is sickle cell crisis treated?

Answer 41

Opiate, hydrate, oxygen, red cell exchange transfusion if severe crisis

Question 42

How is sickle cell anaemia managed long term?

Answer 42

Hyposplenism - prophylactic penicillin and vaccination Folic Acid Supplement Hydroxycarbamide - induces HbF production Regular transfusion therapy

Question 43

What is the most common technique for diagnosing thalassaemia?

Answer 43

High power liquid chromatography