6: Haemoglobinopathies

Question 1

Which globin chains are found in

a) adult Hb
b) foetal Hb?

Answer 1

a) 2 alpha, 2 beta

b) 2 alpha, 2 gamma

Question 2

Which type of haemoglobin is most common in adults?

Answer 2

HbA

Question 3

Which chromosomes code for

a) alpha chains
b) beta chains?

Answer 3

a) Alpha chains - chromosome 16

b) Beta chains - chromosome 11

Question 4

Which genetic process causes HbF production to switch to HbA production?

Answer 4

Gene silencing

On chromosomes 16 and 11

Question 5

What is a haemoglobinopathy?

Answer 5

Inherited conditions affecting globin chain synthesis

Question 6

What is the common mode of inheritance of haemoglobinopathies?

Answer 6

Autosomal recessive

Question 7

What is thalassaemia?

Answer 7

Decreased rate of globin chain synthesis

Question 8

What types of thalassaemia affect the rate of production of

a) alpha chains
b) beta chains?

Answer 8

a) Alpha thalassaemia
b) Beta thalassaemia

Question 9

___ ___ are toxic in high concentrations.

Answer 9

Globin chains

Question 10

Accumulation of globin chains leads to ineffective erythropoiesis - what does this mean?

Answer 10

RBC precursors die before they can develop properly due to toxicity

Question 11

How many alpha chain genes exist on chromosome 16?

Answer 11

4

Question 12

How many beta chain genes exist on chromosome 11?

Answer 12

2

Question 13

The more alpha genes which are deleted, the (faster / slower) the rate of alpha globin production.

Answer 13

slower

Question 14

How many alpha genes are lost from chromosome 16 to cause HbH disease?

Answer 14

3

Question 15

What is meant by HbH in HbH disease?

Answer 15

Dysfunctional type of haemoglobin made up of 4 beta chains

because alpha chains aren’t produced fast enough

Question 16

What is the most severe form of alpha thalassaemia?

What is the cause?

Answer 16

Barts hydrops foetalis

Deletion of all 4 alpha genes from chromosome 16

Question 17

Is Barts hydrops foetalis compatible with life?

Answer 17

No

Question 18

What disease is caused by point mutations in the beta globulin genes of chromosome 9?

Answer 18

Beta thalassaemia

Question 19

Which types of haemoglobin are affected by

a) alpha thalassaemia
b) beta thalassaemia?

Answer 19

a) All of them (HbA, HbF etc.) because they all contain alpha chains

b) HbA only

Question 20

What are the three classifications of beta thalassaemia?

Answer 20

Beta thalassaemia trait

Beta thalassaemia intermedia

Beta thalassaemia major

Increasing in severity as you go

Question 21

When does beta thalassaemia major present?

Answer 21

Around 6 months, when HbF should be changing to HbA

Question 22

How is beta thalassaemia major treated?

Answer 22

Blood transfusions to maintain haemoglobin concentration

Question 23

What is a side effect of regular blood transfusions in beta thalassaemia major?

Answer 23

Iron overload

Question 24

How is iron overload secondary to blood transfusions treated?

Answer 24

Iron chelating drugs

chelate: to form a solution and excrete via urine

Question 25

What genetic mutation causes **sickle cell anaemia**?

Answer 25

**Substitution in codon 6 of beta gene in chromosome 9** Glutamine to valine

Question 26

What type of haemoglobin is produced in sickle cell disease?

Answer 26

**HbS** crap structure, crap shape, 'polymerised', damages the cell membrane

Question 27

What happens if you have a **heterozygous** sickle cell mutation?

Answer 27

**Sickle cell trait** Most likely asymptomatic but you can pass the gene on

Question 28

What is the mode of inheritance of **sickle cell anaemia?**

Answer 28

**Autosomal recessive**

Question 29

Sickle cells have a shortened ___ \_\_\_. What process does this cause?

Answer 29

**shortened life span** **haemolysis**

Question 30

What is an **acute problem** seen in sickle cell anaemia?

Answer 30

**Infarctions** caused by sickle cells occluding circulation **- sickle cell crisis** Can affect spleen causing **hyposplenism**

Question 31

What are some **triggers** of **sickle cell crisis**?

Answer 31

**Hypoxia** **Dehydration** **Cold** **Infection**

Question 32

How is a **sickle crisis** managed?

Answer 32

**Analgesia** **Hydration** **Oxygen** **Blood transfusion** if severe

Question 33

What is a complication of **hyposplenism** secondary to sickle cell anaemia?

Answer 33

**Infection**

Question 34

What are the two main causes of microcytic anaemia?

Answer 34

**Iron deficiency** **Thalassaemia** less common: congenital sideroblastic anaemia, lead poisoning

Question 35

What would be seen on a FBC of a patient with **thalassaemia?**

Answer 35

**Microcytic hypochromic anaemia**

Question 36

Sickle cell anaemia and thalassaemia are ___ for in pregnant women and their partners.

Answer 36

**screened**

Question 37

What is the mode of inheritance of most types of haemoglobinopathy?

Answer 37

**Autosomal recessive**

Question 38

Which types of haemoglobin are affected in a) alpha thalassaemia b) beta thalassaemia?

Answer 38

**a) HbA, HbA2 and HbF** (i.e all of them) **b)** **HbA only**

Question 39

The loss of **up to** **\_\_\_ alpha globin genes** results in asymptomatic alpha thalassaemia.

Answer 39

**up to two**

Question 40

What type of anaemia does thalassaemia cause?

Answer 40

**Microcytic, hypochromic anaemia**

Question 41

Both **iron deficiency** and **thalassaemia** cause microcytic anaemia. How would you differentiate them?

Answer 41

**Check ferritin levels** Low - probably iron deficiency

Question 42

What are the clinical features of **HbH disease**?

Answer 42

**Anaemia** **Splenomegaly** **Jaundice**

Question 43

What occurs in the fingers of sickle crisis patients?

Answer 43

**Dactylitis** painful inflamed digits