Haemoglobinopathies

Question 1

The major form of haemoglobin in adults is HbA. This is composed of which haemoglobin chains?

Answer 1

2 x alpha and 2 x beta

Question 2

The minor form of haemoglobin in adults is HbA2. This is composed of which haemoglobin chains?

Answer 2

2 x alpha and 2 x delta

Question 3

The major form of haemoglobin the the foetus is HbF. This is composed of which haemoglobin chains?

Answer 3

2 x alpha and 2 x gamma

Question 4

Alpha genes are located on which chromosome? How many of these genes are present per chromosome?

Answer 4

Chromosome 16- 2 genes are located on each chromosome (i.e. 4 per cell)

Question 5

Beta genes are located on which chromosome? How many of these genes are present per chromosome?

Answer 5

Chromosome 11- 1 gene is located on each chromosome (i.e. 2 per cell)

Question 6

Adult levels of haemoglobin should be reached by what age?

Answer 6

6-12 months

Question 7

How are haemoglobinopathies usually inherited?

Answer 7

Autosomal recessive

Question 8

In which type of haemoglobinopathy is there a decreased rate of structurally normal haemoglobin synthesised?

Answer 8

Thalassaemia

Question 9

In which type of haemoglobinopathy is there a normal rate of structurally abnormal haemoglobin synthesised?

Answer 9

Structural haemoglobin variants

Question 10

What type of anaemia is seen in individuals with thalassaemia?

Answer 10

Microcytic hypochromic anaemia

Question 11

In thalassaemias, unbalanced accumulation of one type of globin chain leads to ineffective erythropoiesis which is toxic- this leads to what complication?

Answer 11

Haemolysis

Question 12

What is the phenotype if an individual has 2 or 3 alpha genes present instead of the usual 4?

Answer 12

Alpha thalassaemia trait

Question 13

What is the phenotype if an individual has 1 alpha gene present instead of the usual 4?

Answer 13

HbH disease

Question 14

What is the phenotype if an individual has no alpha genes present instead of the usual 4?

Answer 14

Hb Bart’s hydrops foetalis

Question 15

Do individuals with alpha thalassaemia trait usually have any symptoms? Do they require any treatment?

Answer 15

They are usually asymptomatic and don’t require any specific treatment

Question 16

Individuals with alpha thalassamia trait may have a mild microcytic hypochromic anaemia. It is important to distinguish this from iron deficiency anaemia- how would this be done?

Answer 16

Ferritin will be normal in anaemia due to alpha thalassaemia trait

Question 17

What is HbH?

Answer 17

Haemoglobin formed from 4 beta chains, that cannot carry oxygen

Question 18

Red cell inclusions of HbH can be seen with special stains. How are these often described?

Answer 18

Golf ball appearance

Question 19

What are some potential clinical features of HbH disease?

Answer 19

Moderate-severe anaemia, splenomegaly, jaundice

Question 20

How are severe cases of HbH disease treated?

Answer 20

Splenectomy +/- transfusions

Question 21

What is the typical outcome of Hb Bart’s hydrops foetalis?

Answer 21

Almost always incompatible with life

Question 22

What is the phenotype of an individual who has one reduced or one absent beta chain?

Answer 22

Beta thalassaemia trait

Question 23

What is the phenotype of an individual who has one reduced and one absent or two reduced beta chains?

Answer 23

Beta thalassaemia intermedia

Question 24

What is the phenotype of an individual who has two absent beta chains?

Answer 24

Beta thalassaemia major

Question 25

Individuals with beta thalassaemia may have an increased production of which type of haemoglobin?

Answer 25

HbA2

Question 26

What is the clinical picture of an individual with beta thalassaemia trait?

Answer 26

Asymptomatic, with no/mild anaemia

Question 27

What is the clinical picture of an individual with beta thalassaemia intermedia?

Answer 27

Moderate anaemia requiring occasional transfusions

Question 28

What is the clinical picture of an individual with beta thalassaemia major?

Answer 28

Severe anaemia with lifelong transfusion dependency

Question 29

When and how does beta thalassaemia major typically present?

Answer 29

6-24 months with pallor and failure to thrive

Question 30

Skeletal changes, causing a 'hair on end' appearance of the skull, is seen in which haemoglobinopathies?

Answer 30

Beta thalassaemia major and sickle cell anaemia

Question 31

What is a potential treatment for beta thalassaemia major if carried out before complications develop?

Answer 31

Bone marrow transplant

Question 32

What is the main consequence of treating severe thalassaemias with blood transfusions?

Answer 32

Iron overload

Question 33

What is given to prevent iron overload in individuals being treated with frequent blood transfusions?

Answer 33

Iron chelating agents (e.g. desferrioxamine)

Question 34

Sickle cell disorders are caused by a mutation in which gene?

Answer 34

Beta globin gene

Question 35

What is the phenotype of an individual with one normal and one abnormal beta globin gene?

Answer 35

Sickle cell trait (HbAS)

Question 36

What is the main clinical feature of sickle cell trait (HbAS)?

Answer 36

Sickling of red blood cells when exposed to hypoxia

Question 37

What is the phenotype of an individual with two abnormal beta globin genes?

Answer 37

Sickle cell anaemia (HbSS)

Question 38

What is the most common presentation of a sickle cell crisis in children?

Answer 38

Dactylitis

Question 39

How should a sickle cell crisis be treated?

Answer 39

Oxygen, fluids, opiate analgesia +/- antibiotics

Question 40

What treatment option can be used in cases of severe sickle cell crisis to decrease the concentration of HbS and improve tissue perfusion?

Answer 40

Red cell transfusion

Question 41

What effect does long-term sickle cell anaemia have on the spleen?

Answer 41

Causes hyposplenism

Question 42

How should hyposplenism as a result of sickle cell anaemia be treated?

Answer 42

Prophylactic penicillin and vaccinations against pneumococcus, haemophilus and meningococcus

Question 43

What supplements are required for individuals with sickle cell anaemia?

Answer 43

Folic acid

Question 44

How does hydroxycarbamide reduce the severity of sickle cell anaemia?

Answer 44

Induces HbF production

Question 45

What is meant by the term sickle cell disease?

Answer 45

Heterozygosity for HbS and another beta chain mutation

Question 46

What is usually the diagnostic test for haemoglobinopathies?

Answer 46

High performance liquid chromatography

Question 47

What investigation is required to test for alpha thalassaemia trait?

Answer 47

DNA testing