Thalassemia

1. What is thalassemia?

• A group of inherited blood disorders of haemoglobin synthesis;
• Haemoglobin in an adult is formed by 2 α and 2 β

  globin chains. Genetic defect results in ineffective synthesis of a specific globin chain. The disorders are classified according to the particular globin chain that is affected;

• For each type of thalassemia, it is also further classified into ‘major’ or ‘minor’. Individuals with thalassemia major have complete absence of that specific type of globin chain, resulting in severe anaemia. Those with thalassemia minor have impaired production only. They may suffer from mild anaemia but most have no symptoms;
• In Hong Kong, the α and β thalassemias are the 2 most common types. The prevalences of α and β thalassemia minor are ~5% and 3% respectively

2. α-thalassemia major

• The haemoglobin in fetuses (fetal haemoglobin) consists of 2 α and 2 µ chains;
• Fetuses with α-thalassemia major fail to produce any α chain and hence cannot synthesize fetal haemoglobin;
• Affected fetuses suffer from severe anaemia early in pregnancy. As a result of heart failure, the fetuses develop generalized oedema which is called ‘Hydrops fetalis’;
• High risks of intrauterine fetal demise;
• Mother of the affected fetus also has high risks of developing pre-eclampsia;
• Traditionally regarded as a lethal condition. However, repeated intrauterine transfusion has been researched as treatment modality. It helps to build up the haemoglobin levels which may prevent fetal brain damage by anaemia. After delivery, the baby will still need repeated blood transfusion till stem cell transplant can be arranged;
• In-utero stem cell transplantation is being studied as an alternate treatment modality

4. Thalassemia minor (same type) couple & prenatal diagnosis

• Their offsprings have 1 in 4 chance of having thalassemia major, 1 in 2 chance for thalassemia minor and 1 in 4 chance of being normal;
• Antenatal screening through a complete blood picture of the mother’s blood. If the mean cell volume (MCV) is low, further blood investigations from both parents are necessary;
• α-thalassemia minor couple have the options of

1. (i) serial ultrasound screening from 12 weeks of gestation for signs of fetal hydrops

or

1. (ii) invasive prenatal diagnosis by chorionic villus sampling (CVS) or amniocentesis;

• β– thalassemia minor couples need to consider CVS or amniocentesis for prenatal diagnosis as there is no abnormality on ultrasound

5. What if the fetus suffers from thalassemia major?

Prenatal diagnosis counselling is important on the prognosis and various options before and after birth. Some couple will consider a termination of pregnancy, which has to be performed before 24 weeks of gestation in Hong Kong.