Sickle cell disease (SCD) is a group of inherited blood disorders that affect hemoglobin, the protein in red blood cells responsible for carrying oxygen throughout the body. Normally, red blood cells are round, flexible, and move easily through blood vessels. In SCD, a genetic mutation causes the hemoglobin to be abnormal, leading red blood cells to become stiff, sticky, and crescent- or "sickle"-shaped.

These sickle cells die prematurely, leading to a constant shortage of red blood cells (anemia). More dangerously, they can get stuck in small blood vessels, blocking blood flow. This blockage can cause severe pain and serious complications, including organ damage, infections, and stroke.

Causes

SCD is an inherited genetic condition. A child is born with SCD if they inherit a mutated gene for abnormal hemoglobin from both parents. If a child inherits one copy of the sickle cell gene from one parent and a normal gene from the other, they have "sickle cell trait" (SCT) and usually do not experience symptoms of the disease, but they can pass the gene to their children.

SCD is more common in people of African, Mediterranean, Middle Eastern, South Asian, and Central and South American descent.

Types

The most common types of SCD depend on the specific combination of abnormal hemoglobin genes inherited:

HbSS (Sickle Cell Anemia): The most common and often most severe form, where two genes for hemoglobin "S" are inherited.

HbSC: Inheriting a hemoglobin S gene and a gene for another abnormal hemoglobin called "C." This is typically a milder form.

HbS beta-thalassemia: Inheriting a hemoglobin S gene and a gene for beta thalassemia (another type of hemoglobin abnormality). The severity varies depending on the type of beta thalassemia.

There are also rarer types like HbSD, HbSE, and HbSO.

Symptoms

Symptoms typically begin in infancy (around 5-6 months old) and can vary widely among individuals. The main symptoms include:

Painful episodes (sickle cell crises/vaso-occlusive crises): Sudden, severe pain that can occur anywhere in the body, often requiring medical attention. These happen when sickle cells block blood flow.

Anemia: Due to the premature destruction of sickle cells, leading to fatigue, pale skin, shortness of breath, and dizziness.

Increased risk of infections: The spleen, which helps fight infection, can be damaged by sickle cells, making individuals more vulnerable to serious infections.

Swelling of hands and feet (Dactylitis): Often an early symptom in infants.

Delayed growth or puberty: Due to chronic anemia and organ damage.

Vision problems: Blockage of blood vessels in the eyes can damage the retina.

Acute Chest Syndrome: A life-threatening lung complication characterized by chest pain, fever, cough, and difficulty breathing.

Stroke: Blockage of blood flow to the brain by sickle cells.

Organ damage: Over time, various organs (spleen, kidneys, liver, heart, lungs) can be damaged due to reduced blood flow.

Jaundice: Yellowing of the skin and eyes due to rapid red blood cell breakdown.

Diagnosis

SCD is usually diagnosed through:

Newborn screening: All newborns in many countries (including the U.S.) are routinely screened via a heel-prick blood test.

Blood tests: Specifically looking for abnormal hemoglobin (hemoglobin electrophoresis).

Prenatal testing: Can be done during pregnancy by testing amniotic fluid or placental tissue if there's a family history of SCD.