Thalassemia
Thalassemia is a type of haemoglobinopathy in which there is abnormal synthesis of either the alpha globin or beta globin chains which make up haemoglobin. It is one of the most common genetic disorders worldwide. It is inherited in an autosomal recessive pattern. Patients with Thalassemia either have an excess amount of alpha or beta globin chains and suffer from impaired erythrocyte production.
There are 2 main types of thalassemias:
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Alpha thalassemia: mutation in one/both genes encoding the alpha globin protein
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This form is more common in people from the Middle East, China and Southeast Asia.
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Beta thalassemia: mutation in genes coding for the production of beta globin chains
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This type is more common in those of Mediterranean descent.
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Both types of thalassemias can be further classified into subtypes e.g. thalassemia major (homozygous- both genes are faulty) or thalassemia minor (heterozygous- only one gene is affected, these people are known as carriers). There are 4 subtypes of alpha thalassemia as there are 2 alpha globin genes found on each chromosome 16.1
Pathophysiology of Thalassemia
Alpha Thalassemia:
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The pathology arises from a mutation or deletion of one or more alpha globin genes.
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This leads to an excess of beta globin proteins which form an unstable form of haemoglobin leading to chronic haemolytic anaemia
Beta Thalassemia:
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The pathology in this from usually arises from a large number of point mutations which results in a reduction in production of beta globin chains.
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This means that there is an excess of free unbound alpha globin chains which are cytotoxic and lead to haemolysis.
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The increased break down of red blood cells results in increased levels of bilirubin which can cause jaundice or formation of gallstones.1
Diagnosing Thalassemia
Thalassemia is usually diagnosed during pregnancy or soon after birth, but can also be diagnosed afterwards, using a full blood count (FBC), haemoglobin electrophoresis or HPLC. Most thalassemia patients are diagnosed within the first 2 years of life if they show moderate to severe signs and symptoms.
An FBC for the 2 types of thalassemias would show:
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Alpha thalassemia:
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Microcytosis in absence of iron deficiency
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Haemoglobin types may be normal or Haemoglobin H may be seen
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Beta thalassemia:
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Microcytosis with mild anaemia
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Haemoglin A2 or fetal haemoglobin may be seen
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On a blood smear, nucleated immature red blood cells may be seen with anisocytosis
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Iron Studies: it is important to check the ferritin and iron level as iron deficiency anaemia is the main differential for a microcytic hypochromic anaemia. Ferritin levels will be low in iron deficiency anaemia. Iron deficiency anaemia and thalassaemia can co-exist, with iron deficiency exacerbating thalassaemia.
If iron levels are normal, haemoglobin studies such as Haemoglobin electrophoresis or High performance liquid chromatography (HPLC) are performed to detect the amounts of different types of haemoglobin in the blood. For example, in beta thalassaemia major, there is a raised level of HbF (alpha 2 gamma 2).2
Skeletal survery: Thalassaemia may cause bone deformities as the bone marrow expands.3
Genetic studies can also be performed to determine the missing alleles (the genotype) of the disease.
Treatment of Thalassaemia
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If asymptomatic, no treatment is required
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Blood transfusion (frequency of transfusions is dependent on severity)
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Frequent transfusions can cause iron overload - iron deposits in the heart, liver, and endocrine organs (pancreas, pituitary gland) and can result in heart failure, cirrhosis, and diabetes3
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Investigations such as cardiac MRI and liver biopsy may be required to determine iron overload effects
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Iron chelation therapy (ex. desfferioxamine) is carried out to prevent iron overload
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Folic acid supplements
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Stem cell transplant remains the only curative treatment modality for thalassaemia
References
1. Hoffbrand V, Moss P. Hoffbrand's Essential Haematology. Oxford: John Wiley & Sons, Ltd; 2016.
2. Branchaleoni V, Di Pierro E, Motta I, Capellini M. Laboratory diagnosis of thalassemia. International Journal of Laboratory Haematology. 2016;38(S1):32-40.
3. Henderson R. Iron Overload [Internet]. Patient.info. 2016 [cited 22 July 2020]. Available from: https://patient.info/doctor/iron-overload