By Beatrice Nakibuuka
Sickle cell anaemia is most prevalent among African and Mediterranean populations, but it is also found in people from the Caribbean, the Middle East, and Central America. It is estimated to occur in approximately 1 in 500 Africans.
Sickle cell anaemia, often referred to as sickle cell disease, is an inherited form of anaemia where red blood cells, responsible for transporting oxygen from the lungs to the rest of the body, become sickle-shaped. This abnormal shape impairs the cells’ ability to flow smoothly through blood vessels and deliver oxygen efficiently.
According to Dr Francis Ssali, a haematologist at the Joint Clinical Research Centre (JCRC), sickle cells contain abnormal haemoglobin called sickle haemoglobin, or haemoglobin S. This abnormal haemoglobin causes the cells to deform into a crescent, or sickle shape, leading to significant health complications.
These misshapen red blood cells are more likely to clog parts of blood vessels, which restricts the delivery of oxygen to various organs. This can trigger episodes of excruciating pain. Additionally, sickle-shaped red blood cells have a much shorter lifespan than normal round red blood cells. While regular red blood cells live for about 120 days, sickle cells usually die within 10-20 days and cannot be replaced fast enough, resulting in a shortage of red blood cells and causing anaemia.
“The symptoms of sickle cell disease typically manifest in early childhood,” Dr Ssali says, adding: “Some common symptoms include a low count of red blood cells, shortness of breath, delayed growth and development in children, and high blood pressure. While there is no definitive cure for sickle cell anaemia, treatment primarily focuses on reducing the frequency and severity of sickle cell crises.”
Understanding genetic mutation behind sickle cell disease
Sickle cell disease is caused by a mutation in the HBB gene, which encodes the beta-globin chain of haemoglobin. This mutation involves a substitution of glutamic acid (Glu) with valine (Val) at the sixth amino acid position in the beta-globin chain. This small change significantly alters the structure of the haemoglobin protein, causing it to form long chains that distort red blood cells into the characteristic sickle shape.
To develop sickle cell anaemia, an individual must inherit the sickle cell gene mutation from both parents. If both a man and a woman carry the sickle cell gene, their offspring are at high risk of inheriting the disease.
“If a person inherits only one copy of the mutated gene, they are a carrier but will not develop sickle cell disease,” Dr Ssali explains. He adds: “Carriers are at no direct health risk from the disease, but if both parents carry the sickle cell trait, their children have a 25 per cent chance of being born with sickle cell anaemia.”
Difference between sickle cell trait and sickle cell disease
It is important to distinguish between sickle cell trait and sickle cell anaemia. A person with the sickle cell trait carries one copy of the mutated gene but does not exhibit symptoms of the disease. However, if two carriers conceive a child, there is a 25 percent chance that the child will inherit two copies of the mutated gene and develop sickle cell anaemia.
In individuals with sickle cell anaemia, the abnormal red blood cells are less efficient at delivering oxygen to tissues and organs. The body tries to compensate by producing additional haemoglobin, which stimulates the bone marrow to work harder. This overproduction can make bones more fragile and prone to damage. Furthermore, the heart may enlarge in an attempt to increase blood flow and oxygen delivery, leading to cardiovascular strain. The spleen, a key organ in filtering abnormal blood cells, may become enlarged and fibrotic as it collects and destroys sickle cells.
More critically, sickle cells can clog small blood vessels, further restricting blood flow and causing additional complications.
Signs, symptoms of sickle cell disease
The signs of sickle cell disease typically appear around six months of age. The severity of symptoms varies from person to person and can range from mild to severe. Common symptoms include:
- Painful swelling of the hands and feet, known as dactylitis
- Fatigue or irritability due to anaemia
- A yellowish tint to the skin, called jaundice, or yellowing of the whites of the eyes, referred to as icterus, both of which result from the breakdown of red blood cells.
At birth, these symptoms are usually absent because foetal haemoglobin protects red blood cells from sickling. Symptoms generally begin around six months of age when the level of foetal haemoglobin decreases, and sickle haemoglobin takes over.
Prevention, treatment, PGD
While there is no outright cure for sickle cell disease but modern advances in medicine and technology have made it possible to prevent the disease from being passed down to future generations.
Pre-Implantation Genetic Diagnosis (PGD) is one such technological breakthrough. PGD allows for the screening of embryos for a wide range of genetic disorders, including single-gene disorders like sickle cell anaemia.
According to Dr Edward Tamale Sali, a fertility specialist at Women’s Hospital International and Fertility Centre in Bukoto, Uganda, PGD enables doctors to screen embryos for genetic mutations before pregnancy. This screening helps identify which embryos carry the gene mutation for sickle cell disease. “With PGD, we can biopsy each embryo before pregnancy, analyse it for genetic abnormalities, and only transfer the healthy embryos into the uterus for implantation,” Dr Sali explains.
PGD is offered as part of in vitro fertilisation (IVF) treatment, and Dr Sali has overseen over 100 such cases at the Women’s Hospital International and Fertility Centre. By using IVF in conjunction with PGD, couples who are carriers of the sickle cell gene can prevent the transmission of the disease to their offspring.
“PGD can also screen for other genetic conditions, such as Down syndrome, and even determine the gender of the baby for family balancing purposes. While preventing sickle cell disease, couples can also choose the sex of their child if they wish,” Dr Sali says.
How PGD works
Although sickle cell anaemia is caused by a specific mutation in a single gene, it is still necessary to obtain blood samples from both partners to design a PGD probe for embryo screening. While these blood samples are being analysed, the female patient undergoes hormone testing and semen analysis is conducted for the male partner.
Women also take medication to stimulate their ovaries, allowing them to produce multiple eggs. “Having multiple eggs increases the chances of success in IVF treatments. The more eggs we have, the more high-quality embryos we can create for transfer,” Dr Sali says.
Once the eggs are collected via a minor surgical procedure, they are fertilised with sperm in a laboratory to create embryos. These embryos are then screened for sickle cell anaemia, and only the healthy ones are chosen for transfer into the uterus to establish pregnancy.
Process of IVF, PGD for sickle cell disease prevention
As mentioned earlier, preventing sickle cell disease through PGD is done as part of an IVF treatment cycle. Initial tests are carried out to assess the fertility levels of both partners, and a personalised treatment plan is created to optimise success rates.
During this time, the probe design for screening embryos is finalised. This ensures that when the embryos are created, they can be accurately screened for the sickle cell gene mutation.
For patients over the age of 35, Dr Sali recommends considering two IVF cycles to ensure a higher number of embryos. Since ovarian reserves decrease with age, obtaining a larger pool of embryos improves the chances of finding healthy embryos for transfer, thereby enhancing the likelihood of a successful pregnancy.
Costs associated
Preventing sickle cell disease through PGD is a specialised process that includes IVF treatment and genetic screening of embryos. The cost of treatment covers blood sample processing, the design of a PGD probe to screen the embryos, all IVF procedures, and the final embryo transfer.
The price range for this treatment varies widely, depending on the specific needs of the patient and the number of genetic conditions being screened. The total cost can range from USD10,000 to USD50,000.
