Thalassaemia

Question 1

Define thalassaemia

Answer 1

A group of genetic disorders caused by reduced globin chain synthesis

Question 2

What are the causes/risk factors of thalassaemia?

Answer 2

a-Thalassaemia is a group of disorders of haemoglobin synthesis, caused by mutations or deletions in at least 1 of the 4 a-globin genes. This leads to variably impaired a-globin production, with accumulation of excess and unpaired b-globin chains.
• Alpha(0) Thalassaemia: Both a-globin genes on the same chromosome are deleted.
• Alpha(+) Thalassaemia: Only 1 of the 2 a-globin genes on the chromosome is deleted or mutated.

b-Thalassaemia is an inherited microcytic anaemia caused by mutations of the b-globin gene. This leads to decreased or absent synthesis of b-globin, resulting in ineffective erythropoiesis.
• Heterozygous b-Thalassaemia/ b-Thalassaemia Trait
• Homozygous b-Thalassaemia

Question 3

What are the symptoms of thalassaemia?

Answer 3

Beta-thalassaemia major
• Baby becomes profoundly anaemic ~2-3 months as HbF is replaced by HbA
• Failure to thrive
• Poor feeding
• Recurrent infections

Question 4

What are the signs of thalassaemia?

Answer 4

Beta thalassaemia trait
• Mild anaemia
• May be normal

Beta-thalassaemia major
• Pallor
• Malaise
• Dyspnoea
• Mild jaundice
• Frontal bossing
• Thalassaemic facies (marrow hyperplasia)
• Hepatosplenomegaly (pooling and extramedullary haematopoiesis)

Question 5

What investigations are carried out for thalassaemia?

Answer 5

• FBC - a-Thalassaemia - Hb: Low in Hb H and slightly low in a-Thalassaemia trait. Normal in silent carrier. MCV: Low. RBC: Elevated; rises with worsening genetic abnormalities, in parallel with the decline in Hb and MCV. Reticulocytosis.
- b-Thalassaemia - microcytic anaemia, normal to elevated leukocyte and platelet counts from generalised haematopoietic hyperactivity, all decreasing as the spleen enlarges; Reticulocytosis.
• Blood Smear - hypochromia
- Dacrocytes/ Tear Drop Cells
- Heinz Bodies (HbH precipitated)
- Microcytosis
- Target cells
- Polychromasia
• Hb Electrophoresis-
a-Thalassaemia -
Presence of HbH and Hb Bart. Hb Barts (4 g-chains) and HbH (4 β-chains). Both have a higher affinity for oxygen than HbA.
• Bone Marrow Biopsy - hypercellular with erythroid hyperplasia.
• Genetic Testing - rarely necessary. For specific mutations.
• Skull X-Ray - ‘Hair-on-end’ appearance (caused by expansion of marrow into cortex) in b-thalassaemia major.
• Iron Studies - 0ne of first tests; normal –excludes IDA