Thalassaemia is related to a genetic defect in the protein chains that make up haemoglobin. Normal haemoglobin consists of 2 alpha and 2 beta globin chains. Defects in the alpha globin chains lead to alpha thalassaemia. Defects in the beta globin chains lead to beta thalassaemia. Both conditions are autosomal recessive. The overall effect is varying degrees of anaemia, depending on the type and mutation.
In patients with thalassaemia the red blood cells are more fragile and break down more easily. The spleen acts as a sieve to filter the blood and remove older blood cells. In patients with thalassaemia, the spleen collects all the destroyed red blood cells, resulting in splenomegaly.
The bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia. This causes a susceptibility to fractures and prominent features, such as a pronounced forehead and malar eminences (cheek bones).
Potential Signs and Symptoms
- Microcytic anaemia (low mean corpuscular volume)
- Fatigue
- Pallor
- Jaundice
- Gallstones
- Splenomegaly
- Poor growth and development
- Pronounced forehead and malar eminences
Diagnosis
- Full blood count shows a microcytic anaemia.
- Haemoglobin electrophoresis is used to diagnose globin abnormalities.
- DNA testing can be used to look for the genetic abnormality
Pregnant women in the UK are offered a screening test for thalassaemia at booking.
Iron Overload
Iron overload occurs in thalassaemia as a result of the faulty creation of red blood cells, recurrent transfusions and increased absorption of iron in the gut in response to anaemia.
Patients with thalassaemia have serum ferritin levels monitored to check for iron overload. Management of iron overload involves limiting transfusions and performing iron chelation.
Iron overload in thalassaemia causes effects similar to haemochromatosis:
- Fatigue
- Liver cirrhosis
- Infertility
- Impotence
- Heart failure
- Arthritis
- Diabetes
- Osteoporosis and joint pain
Alpha-Thalassaemia
Alpha-thalassaemia is caused by defects in alpha globin chains. The gene coding for this protein is on chromosome 16.
Management:
- Monitoring the full blood count
- Monitoring for complications
- Blood transfusions
- Splenectomy may be performed
- Bone marrow transplant can be curative
Beta-Thalassaemia
Beta-thalassaemia is caused by defects in beta globin chains. The gene coding for this protein is on chromosome 11.
The gene defect can either consist of abnormal copies that retain some function or deletion genes where there is no function in the beta globin protein at all. Based on the type of defect, beta-thalassamia can be split into three types:
- Thalassaemia minor
- Thalassaemia intermedia
- Thalassaemia major
Thalassaemia Minor
Patients with beta thalassaemia minor are carriers of an abnormally functioning beta globin gene. They have one abnormal and one normal gene.
Thalassaemia minor causes a mild microcytic anaemia and usually patients only require monitoring and no active treatment.
Thalassaemia Intermedia
Patients with beta thalassaemia intermedia have two abnormal copies of the beta globin gene. This can be either two defective genes or one defective gene and one deletion gene.
Thalassaemia intermedia causes a more significant microcytic anaemia. Patients require monitoring and occasional blood transfusions. When they require more transfusions, they may require iron chelation to prevent iron overload.
Thalassaemia Major
Patients with beta thalassaemia major are homozygous for the deletion genes. They have no functioning beta globin genes at all. This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood.
Thalassaemia major causes:
- Severe microcytic anaemia
- Splenomegaly
- Bone deformities
Management involves regular transfusions, iron chelation and splenectomy. Bone marrow transplant can potentially be curative.
Last updated January 2020