Sickle Cell Anemia

What is Sickle Cell Anemia: 

Sickle cell anemia is one disorder out of a group of inherited disorders known as sickle cell disease. It affects the shape of red blood cells which transport oxygen to the entire body. Normal red blood cells have a biconcave disc shape and they are flexible so they can easily fit even into smaller blood vessels like capillaries. RBCs affected with sickle cell anemia have a shape like a crescent moon or a sickle. RBCs become rigid and sticky.

Cause: 

Sickle cell anemia is caused by a change in the gene (HBB) which codes for the synthesis of hemoglobin, the iron rich protein which is specifically responsible for carrying oxygen in red blood cells. In a normal hemoglobin, the sixth amino acid in the beta globin chain is glutamic acid. Glutamic acid is a hydrophilic amino acid which means it interacts with the watery environment of the cell and maintains the normal shape. In SCD however, this is replaced by the amino acid valine which is hydrophobic meaning it doesn’t interact with water well. The change from GAG (guanine, adenine, guanine) to GTG (guanine, thymine, guanine) causes the abnormal Hemoglobin S. This hemoglobin forms rigid fibers and distorts the shape of red blood cells.

Symptoms:

1. Anemia. Sickle cells break apart easily and die. Typical red blood cells usually live for about 120 days before they need to be replaced. But sickle cells usually die in 10 to 20 days, leaving a shortage of red blood cells. This is known as anemia. Without enough red blood cells, the body can't get enough oxygen. This causes fatigue and weakness in the body.
2. Periodic episodes of extreme pain, called pain crises, are a major symptom of sickle cell anemia. Pain develops when sickle-shaped red blood cells block blood flow through tiny blood vessels to the chest, abdomen and joints. Some people with sickle cell anemia also have chronic pain from bone and joint damage, ulcers, and other causes.
3. Sickle-shaped red blood cells block blood circulation in the hands and feet, which can cause them to swell.
4. The spleen is important for protecting against infections. Sickle cells can damage the spleen, raising the risk of developing infections. Babies and children with sickle cell anemia commonly receive vaccinations and antibiotics to prevent potentially life-threatening infections, such as pneumonia.
5. Large scale organ failure and death of cells
6. Slowed growth in children and delayed puberty
7. Vision problems.

(Source: Mayo Clinic)

 Treatments:

Current treatments for sickle cell anemia focus on managing symptoms, preventing further complications and offering curative options. Treatments include oral medication like hydroxyurea, bone marrow transplant, steam cell transplant, blood transfusions, gene therapy and taking L-glutamine. 

Hydroxyurea is an antimetabolite medication used in sickle cell disease treatment. It increases total and fetal hemoglobin in children with SCD. The increase in fetal hemoglobin prevents sickling of RBCs. Hydroxyurea also reduces levels of circulating leukocytes, which decreases the adherence of neutrophils to the vascular endothelium. In turn, these effects reduce the incidence of pain episodes and acute chest syndrome episodes.

Allogeneic hematopoietic stem cell transplantation (HSCT) can cure SCD. Most transplants are performed in younger patients, and results are better in that population: an international survey of human leukocyte antigen (HLA)–identical sibling HSCT found that median age at transplantation was 9 years, and the 5-year overall survival rate was 95% for children under age 16 and 81% for those age 16 and older; the 5-year graft-versus-host disease (GVHD)–free survival rate in those age groups was 86% and 77%, respectively.

One form of gene therapy is the use of CRISPR which is a gene editing tool that directly and precisely changes the genes causing SCD. It can be used in vivo or injected into the patient’s body to edit genes so the body makes functional hemoglobin. Or it can be used ex vivo where stem cells from patient are extracted and edited in the lab. Then they are injected back. In a clinical trial, 93.5% of patients achieved freedom from severe vaso-occlusive crisis (which is a major symptom of SCD) according to the National Institutes of Health (NIH). 

(Source: Medscape)

Global prevalence and mortality rates:

SCD affects an estimate of around 8 million people around the world. A significant portion of these cases, around 80%, are found in sub-Saharan Africa according to the World Health Organization (WHO). It is the 12th leading causes of infant mortality and death in age group of under 5. Total deaths due to sickle cell anemia are estimated to be around 376,000. The prevalence of this disease in India is around 0.4 %. The sickle cell gene is found predominantly in Equatorial Africa and amongst the Negro population in the United States. It has also been reported in Saudi Arabia, the Middle East, Southern India and Iran. It is most prevalent in the US, Nigeria, Congo and India. In Europe it affects every 5 in 10,000 people. 

(Source: National Institutes of Health (NIH))