Haemoglobinopathies

Question 1

Describe the structure of haemoglobin

Answer 1

Tetramer made of 2 alpha globin like chains and 2 beta globin like chains - one haem group attached to each globin chain

Question 2

HbA

Answer 2

2 alpha chains and 2 beta chains

Question 3

HbA2

Answer 3

2 alpha chains and 2 delta chains

Question 4

HbF

Answer 4

2 alpha chains and 2 gamma chains

Question 5

Which is the major form of haemoglobin present in adults?

Answer 5

HbA (97%)

also HbA2

Question 6

Alpha like genes are on which chromosome?

Answer 6

Chromosome 16

Question 7

Beta like genes are on which chromosome?

Answer 7

Chromosome 11

Question 8

Which type of globin makes up fetal hemaglobin?

Answer 8

HbF (2 alpa, 2 delta)

-fetal haemoglobin tails off in early life, within first few months

Question 9

What are haemoglobinopathies?

Answer 9

Hereditary conditions affecting globin chain synthesis

Question 10

Thalassaemias

Answer 10

Decreased rate of globin chain production

Question 11

Structural haemoglobin variants of haemoglobinopathies

Answer 11

Normal production rate but abnormal globin chain produced (variant haemoglobin e.g. HbS)

Question 12

Alpha thalassemia

Answer 12

Alpha chains affected

Question 13

Beta thalassaemia

Answer 13

Beta chains affected

Question 14

Inadequate Hb production leads to which type of anaemia

Answer 14

Microcytic hypochromic anaemia

Question 15

Unbalanced accumulation of globin chains leads to _____

Answer 15

Ineffective erythropoiesis and haemolysis

Question 16

Endocrine dysfunction that can result from iron overload

Answer 16

• Impaired growth and pubertal development
• Diabetes
• Osteoporosis

Question 17

Cardiac disease that can result from iron overload

Answer 17

• Cardiomyopathy

- Arrythmias

Question 18

Liver disease that can result from iron overload

Answer 18

• Cirrhosis

- Hepatocellular cancer

Question 19

Inadequate Hb production leads to which type of anaemia?

Answer 19

Microcytic hypochromic anaemia

Question 20

Genetic mutations that cause thalassaemias -discuss deletions and point mutations

Answer 20

Deletions are common (deletion of 1 gene = reduced synthesis, deletion of both genes = absent synthesis)

Point mutations are rare and cause a more profound alpha chain reduction, so these are called non-deletional alpha thalassaemia

Question 21

Management of HbH disease

Answer 21

Mild: transfusion only needed at times of intercurrent illness
Severe cases: transfusion dependent

Splenectomy may reduce transfusion need in severe cases

Folic acid supplementation

Question 22

HbA chains in Hydrops Fetalis?

Answer 22

There are no chains in hydrops fetalis!!! (no alpha genes inherited from either parent, HbA can’t be produced!)

Question 23

Prevention of Barts Hydrops Fetalis?

Answer 23

Antenatal screening to identify parents at high risk (i.e. both possible alpha0 carriers)

• family origin questionnaire and FBC
• further testing if from high-risk area or abnormal RBC indices

Question 24

Name a procedure that could do the following:

• quantify HbA, HbA2 and HbF
• Identify abnormal haemoglonins e.g. HbH
• ecludes beta thal trait etc

Answer 24

High performance liquid chromatography (HPLC) or haemoglobin electrophoresis

Question 25

Target cells

Answer 25

Alpha thalassaemia

Question 26

Diagnosis of thalassaemia

Answer 26

Alpha thalassaemia trait usually suspected from red cell indices and ethnic origin

-blood film, TARGET cells, anisopoikilocytosis

Molecular testing needed to confirm alpha thal trait and determine mutation involved

-PCR used to screen for common mutations

Question 27

How does HbH behave in terms of genetic fashion?

Answer 27

Autosomal recessive fasion

Question 28

Mutation which usually causes beta thalassaemia

Answer 28

Usually caused by point mutations (opposite of alpha thal)

Question 29

Mutations which usually cause alpha thalassaemia?

Answer 29

Deletions (point mutations are rare, unlike beta thalassaemia)

Question 30

Diagnosis of beta thalassaemia trait

Answer 30

Raised HbA2 is diagnostic

-low MCV/MCH

Question 31

Laboratory features of beta thalassaemia major

Answer 31

• Moderate to severe anaemia (Hb 30-90g/l)
• very low MCV/MCH
• reticulocytosis
• film: anisopoikilocytosis and target cells
• HPLC: mainly HbF present, small amounts of HbA, HbA2 often elevated