Sickle cell disease

Sickle cell disease (SCD) is a group of inherited blood disorders. These disorders affect how hemoglobin works in red blood cells. Hemoglobin is the protein that carries oxygen through the body. The most common form is known as sickle cell anaemia. In this condition, red blood cells change their shape. Instead of being round and flexible, they become stiff and curved.

This shape resembles a sickle, which is a curved tool used in farming. Because these cells are rigid, they struggle to move through the body. This leads to serious health challenges for many people.

The disease is caused by a specific genetic mechanism. A person must inherit two abnormal copies of the β-globin gene. They receive one abnormal gene from each parent.

This pattern is called autosomal recessive inheritance. These genes cause the body to produce hemoglobin S (HbS). When oxygen levels drop, the HbS molecules undergo polymerization. This means they stick together into long, rigid structures.

These structures force the red blood cell to transform from a flexible saucer shape into a stiff sickle shape. This change can be triggered by dehydration, high altitude, stress, or temperature changes.

Once the cells become sickle-shaped, they cause several types of medical crises. A vaso-occlusive crisis (VOC) occurs when these stiff cells block capillaries. These tiny blood vessels are too narrow for the rigid cells to pass through. This blockage restricts blood flow, causing ischaemia, which is a lack of oxygen to tissues. This results in extreme pain in the chest, back, legs, or arms.

Another emergency is a splenic sequestration crisis. This happens when sickled cells block the spleen, which acts as a blood filter. The spleen can swell with blood, causing a dangerous drop in hemoglobin levels. This most commonly affects young children, often around 1.4 years of age.

Other serious complications can affect the entire body. Acute chest syndrome is a major concern involving the lungs. It is caused by a vaso-occlusive crisis in the lungs and accounts for about 25% of deaths. Aplastic crises can also occur if a person catches parvovirus B19. This virus attacks the cells that produce new red blood cells. Because people with SCD already have shorter red cell lifespans, this can lead to life-threatening anaemia.

Other long-term issues include strokes, kidney failure, and vision problems like retinal detachment.

Scientists have a long history of studying this condition. An American physician named James B. Herrick first described the disease in 1910. In 1949, E. A. Beet and J. V. Neel discovered how the disease is passed through genes. A major discovery occurred in 1954 regarding the relationship between genetics and malaria. Researchers found that people with a single abnormal gene, called a carrier, have some protection against malaria.

This protection is likely why the sickle cell trait persists in populations where malaria is common.

The impact of sickle cell disease is global. It is estimated to affect about 7.7 million people worldwide. About 80% of all cases occur in sub-Saharan Africa. It is also found in parts of India, West Asia, and North Africa.

The disease causes an estimated 34,000 direct deaths every year. It is also a contributory factor in 376,000 other deaths. Without medical care, many people do not reach adulthood. However, with modern healthcare, the median life expectancy is between 58 and 66 years.

Medical treatments have evolved significantly over time. Doctors use vaccinations, antibiotics, and folic acid to manage symptoms. Some patients receive blood transfusions or medications like hydroxycarbamide. In 2023, a major breakthrough arrived with new gene therapies. These therapies involve the genetic modification of blood-forming stem cells in the bone marrow. This allows doctors to address the root cause of the disorder at a cellular level.

This represents a new era in treating inherited blood diseases.