Genes carry the information that determines traits, like the color of your eyes, how quickly your hair grows, how tall you are, and more. Everything about you is determined by genes that are passed down from parents to each child. Each parent contributes one copy of a gene, so you receive two copies of genes.

Hemoglobin (pronounced heem-oh-glow-bin) is the protein in red blood cells (RBCs) that carries oxygen from the lungs to the body and carries carbon dioxide from the body to the lungs to be breathed out.

Since sickle cell disease is a disorder that is inherited from your parents, you also receive two copies of the hemoglobin gene – one copy of the hemoglobin gene from each parent. The two copies form your hemoglobin genotype and determine whether your red blood cells will sickle and how often.

Inheriting Sickle Cell

Unaffected hemoglobin is labeled with the letter A. When there is a gene mutation, or variant, in the hemoglobin gene, like in sickle cell disorders, hemoglobin acts slightly differently (their own change in shape changes the shape of red blood cells). The sickle cell gene variant is labeled ‘S’. You receive a copy of each gene from your biological mother and one copy from your biological father; therefore, your genes are labeled with two letters, which is called your genotype. Here are some examples:

• AA means a person is unaffected by sickle cell disease. They inherited two nonmutated hemoglobin genes, one from each parent.
• AS means a person has one nonmutated gene and one sickle gene. This is known as sickle cell trait.
• SS means a person has two sickle genes, one from each parent. This is known as sickle cell anemia.
• SC, SD^{Los Angeles}, SO^Arab, Sβ₊(beta-plus)-thalassemia and Sβ₀(beta-zero)-thalassemia means a person has one sickle gene and another hemoglobin mutation. These are generally known as sickle cell disease, although they may have another associated name.

You will often see the two-letter genes with “Hb” in front of the two letters. For example, HbAS is sickle cell trait.

These illustrations help explain how genetics works when determining sickle cell inheritance.

• If both parents have HbSS, there is a 100% chance that each child will have HbSS
• If one parent has HbSS and the other parent has HbAA, there is a 100% chance that each child will have HbAS
• If one parent has HbSS and the other parent has HbAS, there is a 50% chance of having a child with HbAS and a 50% chance of a child with HbSS
• If each parent has HbAS, the inheritance patterns will vary. With each pregnancy, three outcomes could occur:
  • The child has a 25% chance of having HbSS
  • The child has a 50% chance of having HbAS
  • The child has a 25% chance of having HbAA

There are many types of sickle cell disease. Any hemoglobin gene mutation (like hemoglobin C and β₀/β+ thalassemia) paired with the sickle gene “S” is usually generally named sickle cell disease. They can also have another name like sickle SC disease or hemoglobin SC disease for HbSC; or Sβ₀/β+ (beta-zero/beta+plus) thalassemia or sickle β₀/β+ thalassemia disease for HbS β₀/β+. Other rare types of sickle cell disease include sickle SD disease, sickle SE disease, and sickle SO disease. There are hundreds of hemoglobin mutations, which means new, but rare forms of sickle cell disease continue to be discovered.

The most common types of sickle cell disease are sickle cell anemia (HbSS), sickle SC disease (HbSC), sickle beta-plus thalassemia (Hb Sβ+-Thal), and sickle beta-zero thalassemia (Hb Sβ₀-Thal).

Global Presence

Sickle cell disease and sickle cell trait affects millions of people globally and is particularly common amongst those with ancestry from Sub-Saharan Africa.

Sickle cell disorders also more common in:

• Hispanics from Central, South America, and the Caribbean
• People of Middle Eastern descent (Saudi Arabia, Bahrain and Oman)
• People of Mediterranean descent (Turkey, Greece, and Italy)
• People of Southeast Asian descent (India)

About 5% of the world’s population carries a hemoglobin mutation gene—most of them being the sickle gene mutation and thalassemia gene mutation. There are twice as many babies born with sickle cell anemia (SS) than all of the major thalassemia types combined. These conditions are common in regions that have widespread malaria because the heterozygous sickle mutation (e.g., HbAS and HbSC) provide protection against malaria in some cases. Anemia, a symptom of sickle cell disease, is usually attributed to malaria in Sub-Saharan Africa.

United States Demographics

In the United States, the CDC estimated that:

• SCD affects approximately 100,000 Americans.
• About 1 in 13 Black or African American babies is born with sickle cell trait (SCT).
• SCD occurs in about 1 out of every 365 Black or African American births.
• SCD occurs in about 1 out of every 16,300 Hispanic-American births.
• SCD occurs in about 1 out of every 100,000 Caucasian births.

It is hypothesized that the sickle gene has been present in Africa for as long as 7,000 years. Although sickle cell disease was widely known in Africa, it was not discovered in Western medicine until 1910.

Walter Clement Noel was the first person described with sickle cell disease. Noel was a dental student from Grenada, who studied in Chicago. When experiencing a pain episode, Noel sought out medical care at a neighborhood hospital. Noel was assigned to Dr. Ernest Irons who was a medical resident of a well-known cardiologist, Dr. James Herrick.

When Dr. Irons looked at Noel’s blood under a microscope, he saw red blood cells shaped like a ‘sickle’ as medical literature describes. Dr. Herrick later published the first paper entitled, “Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia.” Irons continued to care for Noel until he returned to Grenada, where he died in May 1916 at the age of 32 years from acute chest syndrome.

In 1949, Linus Pauling and his collaborators published a study in the journal Science entitled “Sickle Cell Anemia, a Molecular Disease.”

In 1956, Dr. Vernon Ingram and Dr. J.A. Hunt showed that a mutation replacing one amino acid with another was the main cause for the abnormal hemoglobin and changed shape of red blood cells in sickle cell disease.

In 1983, the first successful cure for sickle cell disease was reported when a bone marrow transplantation meant to cure a child with acute leukemia also cured her sickle cell disease.

Sickle Cell Date Observances

Thanks to the significant early efforts of Madame Edwidge Ebakisse Badassou from the Democratic Republic of Congo and Madame Antoinette Sassou N’Guesso from the Democratic Republic of Congo, and Madame Viviane Wade from Senegal, sickle cell disease is received greater awareness and is recognized by the World Health Organization as a public health problem that requires research, awareness, and annual recognition.

Today, we observe Sickle Cell Disease and those affected by the disease annually.

Sickle Cell Disease

Signs and symptoms of sickle cell disease are different from person to person and can range from mild to severe. There are many factors that impact how severe sickle cell disease may be—even siblings may not have the same degree of severity.

Sickle cell symptoms start around one year of age; though, with severe sickle cell disease, symptoms can start as early as four to six months of age. One of the first signs a baby has sickle cell disease, other than screening, is dactylitis, which is the swelling of their hands and feet. In countries where there is no screening, dactylitis, severe infections, and anemia may help diagnose a newborn or individual with sickle cell disease. However, without the necessary early screening, most young children die before the age of three and many do not get a diagnosis until school age or even early adolescence, particularly if they have SC disease.

Many of the complications found in sickle cell disease result from hemolysis, which is the rapid breakdown of red blood cells. Other complications of sickle cell disease result from anemia and the stickiness of red blood cells that blocks blood flow. Complications can be acute, which typically develop suddenly, or chronic, which develop over time.

Sickle Cell Trait

Under extreme conditions, like being at a high altitude with reduced atmospheric pressure, oxygen levels, and oxygen pressure in the air, red blood cells can sickle in those with sickle cell trait and lead to medical complications. Additionally, chronic kidney disease and a very rare form of kidney cancer (renal medullary carcinoma) are also associated with sickle cell trait.

During Pregnancy

Testing for sickle cell can be performed during pregnancy. A prenatal test can be conducted to find out if the fetus has sickle cell disease or sickle cell trait by collecting a sample of the amniotic fluid, the fluid around the baby. Chorionic villus sampling, a DNA test, is an additional way to test the baby’s sickle cell genetic status. Additionally, there is also ongoing research to test maternal blood for fetal DNA.

Newborn Screening

Newborn screening consists of a heel-prick blood sample that is then analyzed for abnormal hemoglobin. This test can identify both sickle cell disease and sickle cell trait. Universal newborn screening for sickle cell is required in every state in the United States. In the European Union, not all countries screen for sickle cell disease. In sub-Saharan Africa, there is very little screening.

Blood Test

For children and adults who are unsure if they have the sickle cell gene or any abnormal hemoglobin, they can find out with a simple blood test, provided by a healthcare provider. A hemoglobin electrophoresis test can determine if an abnormal hemoglobin gene is present, however, if a rare abnormal hemoglobin gene is detected, additional tests may be needed to confirm genetic status.

Treatment options for sickle cell disease vary based on available resources and the associated complications. Below are some commonly recommended preventative measures and treatments for sickle cell disease complications.

Patients are highly advised to consult with their primary care provider or hematologist to ensure which treatment option, preventative option, and clinical studies are right for them.

Below are a few digital information resources for those living with sickle cell disease and their loved ones.