Alpha thalassaemia

Purpose of the test

The alpha thalassaemias are a group of disorders characterised by a reduction in alpha globin synthesis. Each chromosome carries two copies of the alpha globin gene. Severe forms of the disease (α0 thalassaemias) have two alpha globin genes deleted e.g. --SEA, --MED, -(α)20.5, --FIL, --THAI. Mild types (α+ thalassaemias) have one alpha gene deleted e.g. -α3.7 and -α4.2 or is non-functional. Alpha thalassaemia is most frequently due to deletions, although α+ thalassaemia can also be caused by point mutations (non-deletional alpha thalassaemia). The homozygous state for α0 thalassaemia results in haemoglobin (Hb) Barts hydrops fetalis syndrome which is lethal, leading to stillbirth or early neonatal death. Prenatal diagnosis for the homozygous state is offered. α0 thalassaemia is particularly common in South East Asia and in the eastern Mediterranean countries. It is extremely rare in Africa, the Caribbean and India where α+ thalassaemia predominates. The compound heterozygous condition of α0/ α+ thalassaemia results in Hb H disease in which three out of the four alpha globin genes are deleted or non-functional. Patients with Hb H disease lead a relatively normal life and prenatal diagnosis is not required.

Triplicated alpha thalassaemia (ααα/αα) results from the recombination of homologous regions within the alpha globin gene. It is clinically relevant in combination with beta thalassaemia carrier state leading to a more severe form of the disease.

Non-deletional alpha thalassaemia is caused by point mutations, insertions and small deletions. This tends to give rise to a more severe reduction in alpha chain synthesis than for the deletional forms of alpha thalassaemia. In general there is good correlation between the phenotype and the genotype, although this can be obscured by iron deficiency.

Identification of the alpha thalassaemia mutations, including triplicated alpha thalassaemia is by multiplex Gap PCR. DNA sequencing is used to identify non-deletional alpha thalassaemia mutations.

Sample Requirements

Volume of blood anticoagulated with EDTA:

Adult (16 years and above) 10-15 mls

Children (2-15 years) 5 mls

Infants (0-2 years) 2 mls

Presence of heparin anticoagulant will inhibit PCR applications.

Clotted samples are unsuitable for DNA analysis.

For prenatal diagnosis please refer to section for sample requirements.

Storage and Transport

Blood should be stored at 4°C where possible. Send at room temperature by first class post.

If possible, please complete the request form attached and send as a hard copy (do not send electronically) with the sample. This will ensure all relevant information is available and will aid us in processing your test.

PDF Request Form

Download Alpha Thalassaemia Request Form

Turnaround Time

2 weeks

Time Limit for Extra Tests

5 years

Factors affecting results or interpretation

Presence of heparin anticoagulant will inhibit PCR applications.

Clotted samples are unsuitable for DNA analysis.

Samples must be clearly labelled with the patients first name, surname, D.O.B, hospital number and the date the sample was taken. The details on the sample must correspond to the request form. Unlabelled samples will not be accepted.