Thalassaemia

Question 1

Define thalassaemia

Answer 1

Group of genetic disorders characterised by a defect in globin chain synthesis

Question 2

Aetiology of thalassaemia

Answer 2

Alpha - Mutation in alpha globin gene (Chr 16) -> reduced/impaired production

Beta - Mutation in beta-globin gene (Chr 11) -> reduced/absent synthesis -> ineffective erythropoiesis. Autosomal recessive inheritance

Question 3

What are the types of alpha thalassaemia

Answer 3

1-2 gene deletion: Microcytic hypochromic red cells, no anaemia - Alpha (+)
3 gene deletion: Microcytic hypochromic anaemia, splenomegaly
4 gene deletion: Hb Barts and intrauterine death (hydrops fetalis) - Alpha (0)

Question 4

What are the types of beta thalassaemia

Answer 4

Thalassaemia Major → No globin production, homozygous, both copies affected, B0/B+
Thalassaemia Intermedia → Mild defect in synthesis → reduced alpha chains or increased gamma chains
Trait → Carrier, asymptomatic, mild microcytic anaemia, raised RBC
HbE beta

Question 5

Epidemiology of thalassaemia

Answer 5

Most common in Cyprus, Mediterranean, Middle East etc.
Alpha distribution corresponds to that of Malaria exposure (Sub-Saharan Africa etc.)
Hb Barts most common in SE Asia

Question 6

Presenting symptoms of thalassaemia

Answer 6

Anaemia: fatigue, pallor, dizziness, SOB

Alpha - either asymptomatic (+), jaundice gallstones

Beta- presents at 3-6 months, failure to thrive and prone to infections

Question 7

Signs of thalassaemia

Answer 7

Alpha - normal (+), jaundice, splenomegaly, gallstones, facial dysmorphism, growth retardation (HbH)

Beta - pallor, malaise, dyspnoea, mild jaundice, frontal bossing, hepatosplenomegaly

Question 8

Investigations for Thalassaemia

Answer 8

FBC: microcytic anaemia, platelets + WBC mildly elevated
Iron studies: mormal
Blood film
Hb electrophoresis: Absent or reduced HbA and raised HbA2 + HbF
LFTs - elevated LDH + bilirubin

Genetic testing: confirms (rare)

Skull and long bone XR : widening of diploeic space, facial deformity

Bone Marrow: erythroid hyperplasia

Question 9

What is seen on blood film for thalassaemia

Answer 9

Microcytic, hypochromic RBCs
Poikilocytosis 
Howell Jolly bodies 
Nucleated RBCs
Target cells
Elevated reticulocyte count 

Beta: Alpha globin precipitates and Pappenheimer bodies

Perl’s stain - Pappenheimer bodies demonstrated by blue stain