Thalassaemia

Question 1

What is Thalassaemia

Answer 1

autosomal recessive haemoglobinopathy which causes a microcytic anaemia.

Question 2

Blood counts for alpha thalassaemia

Answer 2

HbA (A2 B2) Reduced
HbA2 ( A2 G2) Reduced
HbF (A2 Y2) Reduced

Question 3

Beta thalassaemia

Answer 3

HbA (A2 B2) Reduced
HbA2 ( A2 G2) Increased
HbF (A2 Y2) Increased

Question 4

Epidemiology of thalassaemia

Answer 4

• Thalassaemia is prevalent in areas with malaria as there is evidence to suggest that thalassaemic red cells provide immunity against the parasite.
• Alpha thalassaemia: Asian and African descent
• Beta thalassaemia: South-East Asian, Mediterranean, and Middle Eastern descent

Question 5

Life expectancy of beta thalassaemia

Answer 5

Alpha and beta have normal life expectancy

Beta thalassaemia major is fatal in the first few years of lifeif untreated, and the leading cause of death is heart failure.

Question 6

What is Alpha-thalassemia

Answer 6

genetic disorder where there’s a deficiency in production of the alpha globin chains of haemoglobin.

autosomal recessive condition

Question 7

Epidemiology of alpha thalassaemia

Answer 7

Common in individuals of Asian and African descent

Question 8

Risk factors for alpha thalassaemia

Answer 8

Family history

Question 9

Why does alpha thalassaemia occur?

Answer 9

occurs due to impaired synthesis of α-globin due to genetic deletions.

Question 10

Alpha thalassaemia trait:

Answer 10

people with 2 gene deletions: mildly anaemic with near-normal haemoglobin electrophoresis

either be caused by:
‘cis’ deletion: mutated genes are on the same chromosome
‘trans’ deletion: mutated genes are on two different chromosomes.

Question 11

HbH alpha thalassaemia:

Answer 11

• people with 3 gene deletions
• unable to form alpha chains.
• The beta chains form tetramers (HbH) > damage erythrocytes causing moderate to severe disease
• HbH cause damage by causing haemolysis as well as having a high affinity for O2 and not releasing O2 to tissues.

Question 12

Hb barts (alpha thalassaemia major)

Answer 12

• people with 4 gene deletions
• die in uterobecause the gamma chains form tetramers (Hb Barts)
• cannot carry oxygen efficiently
• Severe hypoxia leads to high-output cardiac failure and massive hepatosplenomegaly > resulting in oedema all over the body, called hydrops fetalis.

Question 13

WHat is a consequence of hypoxia?

Answer 13

signals the bone marrow, liver andspleen to increase production of RBCs.

This may causebones containing bone marrow, as well as the liver andspleen, to enlarge.

Question 14

Signs of alpha thalassaemia

Answer 14

Usually asymptomatic
- Pallor: due to anaemia
- Jaundice: due to unconjugated bilirubin
- Chipmunk facies: compensatory extramedullary hematopoiesis in the skull causes marrow expansion
- Hepatosplenomegaly
- Failure to thrive

Question 15

Symptoms of alpha thalassaemia

Answer 15

• Shortness of breath: due to anaemia
• Palpitations: due to anaemia
• Fatigue: due to anaemia
• Swollen abdomen: due to hepatosplenomegaly

Question 16

Investigations for alpha thalassaemia

Answer 16

FBC
Blood film
Hb electrophoresis
DNA testing

Question 17

Management of alpha thalassaemia

Answer 17

Regular Blood transfusion: Dependent on Hb level
Iron chelation
Folate supplementaion
Splenectomy
Stem cell transplantation

Question 18

Complications of thalassaemia

Answer 18

HF
Hypersplenism
Aplastic crisis
Iron overload
Pericarditis
Arrhythmias
Gallstones

Question 19

What is beta thalassaemia

Answer 19

Beta thalassaemia is a genetic disorder where there’s a deficiency in the production of the β-globin chains of haemoglobin.

It is an autosomal recessive condition.

Question 20

Epidemiology of beta thalassaemia

Answer 20

Most commonly seen in Mediterranean, African and South East Asian populations.

RF is family history

Question 21

What happens in beta thalassaemia

Answer 21

partial or complete β-globin chain deficiency, due to a point mutation in the beta globin gene present on chromosome 11.

result is either a reduced, or completely absent beta globin chain synthesis.

Question 22

3 possible phenotypes of beta thalassaemia

Answer 22

Beta thalassaemia trait -Normal and reduced beta chain
Beta thalassaemia intermedia - Reduced beta chain/ reduced beta chain or reduced beta chain/absent beta chain

Beta thalassaemia major: absent beta chain/ absent beta chain

Question 23

What happens when there beta globin chain deficiency

Answer 23

• Free α-chains accumulate within red blood cells
• clump together to form intracellular inclusions
• Which damage the red blood cell’s cell membrane, causing haemolysis

causes haemoglobin to spill out of RBCs. Haemoglobin can then be recycled into iron and unconjugated bilirubin.

Question 24

Excess unconjugated biliruin and excess iron leads to

Answer 24

Jaundice
Secondary hemochromatosis

Question 25

What can haemolysis lead to

Answer 25

Hypoxia

Question 26

What age does major beta thalassaemia present

Answer 26

< 2 years old

Question 27

Signs of beta thalassaemia

Answer 27

Usually asymptomatic
- Jaundice: due to unconjugated bilirubin
- Pallor: due to anaemia
- Hepatosplenomegaly
- Chipmunk facies: enlarged forehead and cheekbones
- Failure to thrive

Question 28

Symptoms of beta thalassaemia

Answer 28

• Shortness of breath: due to anaemia
• Palpitations: due to anaemia
• Fatigue: due to anaemia
• Swollen abdomen: due to hepatosplenomegaly
• ## Growth retardation

Question 29

1st line investigation for beta thalassaemia

Answer 29

FBC
Bood film
Hb electrophoresis

Skull x ray
DNA testing

Question 30

Management of beta thalassaemia

Answer 30

Doesnt usually require treatment
Other than that same as aloha

Question 31

Complications of beta

Answer 31

HF
Hypersplenism
Aplastic crisis
Iron overload
Gallstones