Sickle cell disease (HBB gene): inheritance, screening and carriers

Haemoglobin is the protein in red blood cells that carries oxygen. In sickle cell disease, abnormal haemoglobin can clump together when oxygen is low or the temperature falls, and the red cells become sickle-shaped and cannot move normally through small vessels. The NHS Genomics Education Programme lists the consequences: painful crises, dactylitis (swollen hands and feet in infancy), acute chest syndrome, stroke, gallstones, priapism, jaundice, anaemia, and damage to the kidneys and liver over time.

The NHS says symptoms can start from about six months of age and affect everyone differently; for most people they come and go. A sickle cell crisis is sudden severe pain or other symptoms that can last hours, days or weeks, and the NHS names dehydration, a sudden change in temperature and stress as possible triggers.

Over time the spleen stops working properly in most people, which makes infections more of a risk. That is why the programme describes penicillin prophylaxis as vital for children and why the NHS lists antibiotics and vaccinations among the treatments.

The HBB gene on chromosome 11 holds the instructions for the beta part of haemoglobin. The sickle variant is written HbS, and normal adult haemoglobin is HbA. A person with sickle cell disease usually has two sickle copies (HbS/HbS). A person with one sickle copy and one normal copy has sickle cell trait (HbA/HbS), and the NHS Genomics Education Programme says carriers are generally healthy, though anaesthetists need to ensure oxygen levels are maintained.

Because the condition is recessive, the parents of an affected child are usually both carriers. For each pregnancy of two carriers, the programme gives a 25% chance of an affected child, a 50% chance of a carrier child and a 25% chance of a child with two normal copies. Rarely a new variant arises for the first time in the egg or sperm. A sickle gene can also combine with a different haemoglobin variant from the other parent, such as HbC, HbD or beta thalassaemia, giving a different type of sickle cell disorder.

The NHS says people are more likely to inherit sickle cell disease if their background is African, Caribbean, Mediterranean, south or southeast Asian or Middle Eastern, and anyone can ask a GP for a blood test to find out whether they are a carrier.

The NHS says sickle cell disease is usually found during pregnancy or shortly after birth through the screening programmes. Pregnant women are usually offered screening by their midwife before 10 weeks: a blood test that shows whether they carry sickle cell genes that could be passed to the baby. The test is optional, and the NHS says a woman who declines can change her mind later by speaking to her midwife or GP.

The NHS Genomics Education Programme explains that all pregnant women in England are offered a thalassaemia blood test, while those at higher risk of being a sickle cell carrier are offered a test for sickle cell. If a woman is a carrier, partner testing follows. Newborns are screened by the heel prick blood spot test, which can confirm the disease or identify a carrier baby.

For couples who both carry sickle cell, the programme describes prenatal diagnosis by chorionic villus sampling or amniocentesis, genotype testing in the newborn period, and pre-implantation genetic testing, which may be available under the NHS if both partners are carriers and have no unaffected children.

The NHS lists painkillers, penicillin or erythromycin to prevent serious infections, vaccinations, hydroxycarbamide to reduce pain crises, blood transfusions and red cell exchange. Stem cell or bone marrow transplants and gene therapy are sometimes used to cure sickle cell disease, depending on the type, the balance of benefits and risks and the availability of a donor. The NHS Genomics Education Programme says that in February 2025 NICE approved a one-off gene therapy, exagamglogene autotemcel, for older children and adults with a severe form who would be suitable for a stem cell transplant but have no donor.

• Drink plenty of fluids and avoid sudden temperature changes, including very cold water (NHS).

• Keep vaccinations up to date, and try gentle to moderate exercise such as walking or yoga rather than high-intensity exercise.

• Avoid alcohol and smoking, which can increase the risk of acute chest syndrome.

• Follow your care plan and attend check-ups, because the disease raises the risk of stroke, eye problems and organ damage.

The NHS signposts the Sickle Cell Society for information and support, Contact for parent carers of children with a disability, and Sickle Cell and Young Stroke Survivors. Management of children is coordinated by a specialist haemoglobinopathy team and follows national standards of care, the NHS Genomics Education Programme says.