Thalassaemia is a collection of related diseases which are all forms of haemoglobinopathy. The diseases are prevalent in the Mediterranean, Middle East, West Africa, parts of the Indian subcontinent and South East Asia.

As with sickle cell anaemia the reason for the high prevalence of the disease is that carrier forms offer some resistance to malaria infection.

Alpha Thalassaemia

Alpha thalassaemia is caused by defects in the gene for the alpha chain of haemoglobin, which is located on chromosome 16. Each chromosome 16 actually has two copies of the alpha haemoglobin gene so each cell possesses four copies of the gene.

Alpha chains of haemoglobin are required to make both haemoglobin A and haemoglobin F.

If the requisite number of functioning alpha chain genes are not present there is an overproduction of gamma chains and beta chains. This results in haemoglobin molecules which are composed of four beta chains (haemoglobin H) or four gamma chains (haemoglobin Barts). Both of these types of haemoglobin have a very high affinity for oxygen and do not release it properly. In addition haemoglobin H precipitates in older erythrocytes and hastens their demise. A chromosome that has two defective alpha chains is described as alphao trait while a chromosome that has only one abnormal alpha chain is designated alpha+.

Hydrops Syndrome

A fetus that is homozygous for alphao chromosome sixteens (all four alpha chain genes are abnormal) cannot make haemoglobin F (or haemoglobin A). There is anaemia, oedema, marked hepatosplenomegaly (due to erythroid hyperplasia) and a large placenta; pre-eclampsia is common. The condition is incompatible with life and there is either in utero death or postnatal survival for barely an hour.

Haemoglobin H Disease

People who have this variant of alpha thalassaemia possess one alphao and one alpha+ chromosome 16 and therefore have only one normal copy of the alpha chain gene.

The anaemia is usually in the range of 7-10g/dL. Around 5-40% of the haemoglobin is haemoglobin H.

There is variable splenomegaly. The bone changes of growth retardation of beta thalassaemia are unusual.

Patients tend to survive to adulthood. Episodes of haemolysis can be triggered by infection and oxidising drugs.

Beta Thalassaemia Major

The gene for the beta chain of haemoglobin is on chromosome 11. In beta thalassaemia major there is either no production or very little synthesis of beta chains. If beta chain production is impaired an excess of alpha chains is generated. However, unlike the excess beta and gamma chains of alpha thalassaemia, the alpha chains precipitate immediately and mess up erythropoiesis. Any erythrocytes that are created have a decreased survival.

The erythroid precursors can still manufacture haemoglobin F and haemoglobin A2. Haemoglobin F is not very useful post birth.

The anaemia causes a rise in erythropoietin levels and hyperplasia of the erythroid component of the bone marrow.

The disease presents in the first year of life with failure to thrive, poor feeding, intermittent fever and anaemia. If the disease is not treated there is growth retardation and delayed development. Progressive hepatosplenomegaly develops. The expansion of the bone marrow produces bossing of the frontal bones and prominence of the zygomatic bones. The drainage of the sinus and the middle ear can be hindered by the changes in the shape of the skull. The teeth may be malformed and malocclusive.

Recurrent infections can occur.


The anaemia is around 2-8 g/dL and is of the hypochromic, microcytic type. The number of reticulocytes is elevated. The platelet and white cell counts can be normal or reduced.

Haemoglobin electrophoresis discloses the deficiency of beta chains (and is also used to diagnose alpha thalassaemia).

Bilirubin levels may be increased because of increased erythrocyte breakdown.

Urate levels are elevated due to the high cell turnover in the frantically working bone marrow.

Vitamin B12 and folate levels should be checked.

A skull X-ray will reveal a hair on end appearance.


The treatment is with regular transfusions However, this results in iron overload so iron chelation therapy is also required. Possible agents include desferrioxamine.

Beta Thalassaemia Minor

Beta thalassaemia minor is a heterozygous form of beta thalassaemia in which there is only a mild hypochromic, microcytic anaemia and a normal reticulocyte count. The disease is usually asymptomatic, although can become apparent during periods of stress, such as pregnancy.