Haemoglobinopathy

Question 1

Describe the structure of haemoglobin

Answer 1

Tetramer
4 globin chains
One haem group attached to each globin chain

Question 2

What are the 3 main forms of haemoglobin?

Answer 2

HbA: (2-alpha, 2-beta)
HbA2: (2-alpha, 2-delta)
HbF: (2-alpha, 2-gamma)

Question 3

The genes making the alpha protein for haemoglobin are located on which chromosome? How many alpha genes are on each chromosome?

Answer 3

Chromosome 16

2 alpha genes per chromosome

Question 4

The genes making the beta protein for haemoglobin are located on which chromosome? How many beta genes are on each chromosome?

Answer 4

Chromosome 11

1 beta gene per chromosome

Question 5

Which type of haemoglobin - HbA, HbA2 or HbF - is found in a foetus?

Answer 5

HbF

Question 6

When does foetal haemoglobin typically reach adult level following birth?

Answer 6

6-12 months

Question 7

What are haemoglobinopathies?

Answer 7

Hereditary conditions affecting globin chain synthesis

Question 8

What inheritance pattern do haemoglobinopathies generally follow?

Answer 8

Autosomal recessive

Question 9

What are the 2 main groups of haemoglobinopathies?

Answer 9

Thalassaemias

Structural variant

Question 10

What is the problem in thalassaemias?

Answer 10

Decreased rate of globin chain synthesis, resulting in less haemoglobin

Question 11

What is the problem in structural variant haemoglobinopathy?

Answer 11

Normal production of structurally abnormal globin chains, resulting in variant haemoglobin

Question 12

Alpha thalassaemia (affecting alpha-chain synthesis) results from deletion of how many - one or both - alpha genes from chromosome 16?

Answer 12

Either! Can arise due to deletion of one alpha gene or both alpha genes

Question 13

What are the 3 classifications of alpha thalassaemia?

Answer 13

Trait: 1 or 2 genes missing
HbH: 1 alpha gene left
Bart’s hydrops fetalis: no alpha genes

Question 14

Alpha thalassaemia trait is usually asymptomatic. True/False?

Answer 14

True

Mild anaemia and may be mistaken for iron deficiency

Question 15

Describe the clinical features of HbH alpha thalassaemia

Answer 15

Anaemia
Very low MCV
Splenomegaly
Jaundice
Growth retardation

Question 16

What can be seen on special staining of red cells in HbH alpha thalassaemia?

Answer 16

Red cell inclusions (HbH bodies)

Question 17

Describe the clinical features of Bart’s hydrops fetalis alpha thalassaemia

Answer 17

Severe anaemia (can't make Hb)
Cardiac failure
Oedema
Growth retardation
Hepatosplenomegaly
Skeletal abnormality
Death in utero

Question 18

Beta thalassamia only affects beta chains, thus which type of haemoglobin production is affected?

Answer 18

Only affects HbA production

Question 19

What type of mutations are typical in alpha and beta thalassaemias respectively?

Answer 19

Alpha thalassaemia typically due to deletions

Beta thalassaemia typically due to point mutations

Question 20

What are the 3 classifications of beta thalassaemia?

Answer 20

Trait: no or 1 gene missing
Intermedia: 1 gene missing
Major: 2 genes missing

Question 21

What are the laboratory features of beta thalassaemia major?

Answer 21

Very low MCV
Microcytosis, hypochromia
Anisopoikilocytosis
Target cells

Question 22

Beta thalassaemia major is transfusion dependent. True/False?

Answer 22

True

Question 23

Severe thalassaemia can cause extramedullary haematopoiesis. What are the consequences of this?

Answer 23

Hepatosplenomegaly
Skeletal changes
Organ damage
Cord compression

Question 24

What becomes the main cause of mortality from transfusion treatment for beta thalassaemia major?

Answer 24

Iron overload

Question 25

How can iron overload secondary to transfusion be managed?

Answer 25

250mg of iron per unit of red cells | Iron-chelating drug (desferrioxamine)

Question 26

What is the best method of diagnosing thalassaemia? What does it show?

Answer 26

High performance liquid chromatography (HPLC) | Quantifies Hb present and identifies abnormal Hb

Question 27

What is the pathophysiology of sickle cell disorder?

Answer 27

Point mutation in codon 6 of beta-globin gene, causing valine production instead of glutamine, altering the structure of Hb to produce HbS

Question 28

What is the genetic makeup of sickle-cell trait?

Answer 28

One normal beta gene, one abnormal beta gene

Question 29

Is sickle cell anaemia autosomal dominant or recessive?

Answer 29

Autosomal recessive | Requires 2 abnormal beta genes

Question 30

What is a sickle crisis?

Answer 30

Episodes of tissue infarction due to vascular occlusion by sickle cells

Question 31

List some precipitants of a sickle crisis

Answer 31

``` Hypoxia Dehydration Infection Cold exposure Stress Fatigue ```

Question 32

Outline treatment of a sickle crisis

Answer 32

``` Opiate analgesia Hydration Rest Oxygen Antibiotic if infection Red cell transfusion if severe ```

Question 33

What long-term treatment may be given for sickle cell disorder?

Answer 33

Penicillin if hyposplenism Folic acid (increase RBC turnover) Hydroxycarbamide (induce HbF production)