Unlike sickle cell disease and other abnormal haemoglobins the Thalassaemias are defects that affect the quantity (amount) of the globin chain that is synthesised. Therefore in a–thalassaemia syndromes there is a reduction in the rate of synthesis of the a chains and in b–thalassaemia syndromes there is a reduction in the rate of synthesis of the b chains.

Beta (b) thalassaemia
In beta thalassaemia the amount of beta chains produced could be reduced giving rise to beta plus thalassaemia (b+Thal) or not produced at all giving rise to beta zero thalassaemia (b°Thal). The less beta chains produced the more severe the condition will be. Abnormality of one b globin gene results in b-thalassaemia trait, a common benign carrier state. If both genes are affected, the person has either b-thalassaemia major or b-thalassaemia intermedia. The affected gene can either result in no production of b-chains (b°) or very reduced production (b+). If the former is inherited from both parents the individual will have a beta zero thalassaemia major (Hbb°b°Thal) which is a serious haemolytic disease, treated with regular blood transfusions. Thalassaemia intermedia is characterised by a moderately severe anaemia, which does not require regular transfusions. Similar to sickle cell disease this mutation of the beta gene can interact with other mutations of the beta gene and give rise to compound disease states, for example, haemoglobin E beta thalassaemia (HbEb+Thal) or (HbEb°Thal).

Alpha (a) Thalassaemia
In alpha thalassaemia the amount of alpha globin chains of haemoglobin produced could be reduced giving rise to alpha plus thalassaemia (a+Thal) or not produced at all giving rise to alpha thalassaemia major. The less alpha chains produced the more severe the condition will be. Four clinical syndromes are recognised: the silent carrier, with the loss of a single a gene (- a/a a); a-thalassaemia trait, in which two genes are missing (- -/a a) or (- a/(- a); Haemoglobin H disease, in which three a genes are missing (- -/- a); and homozygous a thalassaemia which presents as haemoglobin Barts hydrops fetalis, in which no a genes are present (- -/- -).

The silent carriers of a thalassaemia are fit and not anaemic. Also people who have a thalassaemia trait are fit with a normal or near normal haemoglobin level. However carrier and trait states have genetic implications if couples are planning to have a family. If both partners have a trait condition or a combination of silent carrier and trait then there is a chance that their children can inherit a disease state. Haemoglobin H disease presents as a moderately severe anaemia, varying in severity from patient to patient, lying somewhere between b thalassaemia major and b thalassaemia minor in severity. In Hb Barts hydrops fetalis the affected foetus usually dies before it is born between 23 and 38 weeks of pregnancy, or soon after birth. It is essential to diagnose this condition early in pregnancy as the mother is at serious risk of complications arising during the pregnancy.

If you would like to know more about the thalassaemias visit the following websites:

•  Brent Sickle Cell and Thalassaemia Centre
•  Thalassaemia International Federation (T.I.F.)
•  United Kingdom Thalassaemia Society

What are the Haemoglobinopathies?
What is Sickle Cell Disease?