Beta thalassaemia major (HBB gene): inheritance, screening and treatment

Thalassaemia is a group of inherited conditions affecting haemoglobin, the protein in red blood cells that carries oxygen. The NHS says it mainly affects people of Mediterranean, south Asian, southeast Asian and Middle Eastern origin, and that beta thalassaemia major is the most severe type. Other forms include beta thalassaemia intermedia, alpha thalassaemia major and haemoglobin H disease.

In untreated or poorly treated beta thalassaemia major the NHS Genomics Education Programme describes severe anaemia with an enlarged spleen, bone deformities and iron overload. Children show tiredness, pallor, breathlessness, poor growth, and in untreated disease changes in the facial bones because blood is made outside the bone marrow. The NHS says most people born with thalassaemia have health problems from a few months after birth, and that anaemia and iron overload are the two main problems; iron builds up because of the transfusions used to treat the anaemia and can affect the heart, liver and hormones if untreated.

Beta thalassaemia involves a single gene, HBB, but not all variants have the same effect. The NHS Genomics Education Programme explains that variants which stop beta globin being produced at all (called beta-zero) are more severe than those which allow some production (beta-plus). A person with two beta-zero changes has beta thalassaemia major, a person with certain combinations of beta-plus changes has the moderate intermedia form, and a person with one changed copy has beta thalassaemia minor, or trait.

This explains why the numbers for carrier couples can differ. The NHS says that when both parents carry the faulty gene for beta thalassaemia major, each child has a 1 in 4 chance of being born with the condition. The programme points out that inheritance can be complex because the effect depends on the specific variants. Two beta-zero carriers have a one-in-four chance of a child with beta thalassaemia major, whereas two people with beta-plus changes are extremely unlikely to have a child with major disease apart from new variants.

Children with trait have no symptoms, and the diagnosis matters mainly for family planning. The programme warns that children with trait should not be given iron on the basis of red cell size alone, and that ferritin should be used to check iron status.

The NHS says thalassaemia is often detected during pregnancy or soon after birth. Screening in pregnancy is offered to all pregnant women in England to check whether there is a risk of a child being born with the condition, and some types may be picked up by the newborn blood spot test. Blood tests can be carried out at any age to check for thalassaemia or to see whether you are a carrier, and you can request one from your GP surgery or the nearest sickle cell and thalassaemia centre.

The NHS Genomics Education Programme says a national haemoglobinopathy screening programme identifies potentially affected women in pregnancy and triggers partner testing and referral to haematology. Some families choose partner testing when planning a pregnancy. A woman who is a carrier is at risk of having an affected child only if her partner is a carrier too.

The NHS describes two main treatments. Regular blood transfusions treat and prevent anaemia, and in severe cases they are needed around once a month. Chelation therapy uses medicine to remove the excess iron that builds up as a result of regular transfusions. The NHS Genomics Education Programme says children with thalassaemia major need a regular transfusion programme to prevent complications and to allow normal growth and development.

The only possible cure, the NHS says, is a stem cell or bone marrow transplant, although it is not done very often because of the risks involved. The programme adds that targeted gene therapy for thalassaemia is moving from clinical trials into clinical practice. Management of children is led by a multidisciplinary team in a haemoglobinopathy specialist centre following national standards of care.

Healthy eating, regular exercise and not smoking or drinking too much alcohol can help, according to the NHS.

The NHS describes thalassaemia as a serious condition with a significant impact on a person's life, though the main health problems can often be managed with treatment. Without close monitoring and regular treatment the most severe types can cause serious organ damage and can be life-threatening. Some people also have delayed growth, fragile bones and reduced fertility.

Support is available from the UK Thalassaemia Society, which the NHS describes as the main UK charity for people with thalassaemia. The NHS also notes that your team will pass information to the National Congenital Anomaly and Rare Disease Registration Service, and that you can opt out at any time.