Sickle Cell Disease: Definition and Causes

Definition and Causes

• Sickle cell disease (SCD) is a genetic disorder that affects the production of hemoglobin, a protein in red blood cells that carries oxygen to the body's tissues.
• It is caused by a mutation in the HBB gene that codes for hemoglobin, resulting in the production of abnormal hemoglobin called sickle hemoglobin (HbS).

Pathophysiology

• HbS is less soluble than normal hemoglobin and forms long, rigid fibers that cause red blood cells to become misshapen and take on a sickle-like appearance.
• These sickled cells are more prone to aggregation and can get stuck in small blood vessels, leading to:
  • Vaso-occlusion: Reduced blood flow to organs and tissues, causing pain and damage.
  • Hemolysis: Premature destruction of red blood cells, leading to anemia.

Symptoms

• Anemia: Fatigue, weakness, pale skin, and shortness of breath.
• Vaso-occlusive episodes: Recurring pain in the hands, feet, and joints.
• Increased risk of infections: particularly pneumococcal infections.
• Organ damage: Kidney damage, blindness, and stroke.
• Delayed growth and development in children.

Diagnosis

• Newborn screening: Blood test to detect HbS at birth.
• Hemoglobin electrophoresis: Laboratory test to identify abnormal hemoglobin.
• Genetic testing: DNA analysis to identify the HBB mutation.

Treatment and Management

• Pain management: Medications to alleviate vaso-occlusive episodes.
• Blood transfusions: To increase oxygen delivery and reduce anemia.
• Hydroxyurea: Medication to increase production of fetal hemoglobin, reducing sickling.
• Antibiotics: To prevent and treat infections.
• Bone marrow transplantation: A curative treatment option for some patients.

Complications

• Acute chest syndrome: A life-threatening condition characterized by chest pain, fever, and respiratory distress.
• Stroke: Increased risk of stroke due to blood vessel damage.
• Pulmonary hypertension: Increased blood pressure in the lungs, leading to heart failure.
• Kidney disease: Chronic kidney damage and failure.

Inheritance and Epidemiology

• Autosomal recessive inheritance: A person must inherit two copies of the mutated HBB gene to develop SCD.
• Most common in people of African, Mediterranean, and Middle Eastern descent.
• Affects approximately 1 in 500 African Americans and 1 in 1,000 Hispanic Americans.

Definition and Causes

• Sickle cell disease (SCD) is a genetic disorder that affects hemoglobin production in red blood cells.
• It is caused by a mutation in the HBB gene, resulting in the production of abnormal hemoglobin called sickle hemoglobin (HbS).

Pathophysiology

• HbS is less soluble than normal hemoglobin and forms long, rigid fibers that cause red blood cells to become misshapen and take on a sickle-like appearance.
• Sickled cells are more prone to aggregation and can get stuck in small blood vessels, leading to vaso-occlusion and hemolysis.
• Vaso-occlusion reduces blood flow to organs and tissues, causing pain and damage.
• Hemolysis leads to premature destruction of red blood cells, resulting in anemia.

Symptoms

• Anemia causes fatigue, weakness, pale skin, and shortness of breath.
• Vaso-occlusive episodes cause recurring pain in the hands, feet, and joints.
• Increased risk of infections, particularly pneumococcal infections.
• Organ damage includes kidney damage, blindness, and stroke.
• Delayed growth and development in children.

Diagnosis

• Newborn screening detects HbS at birth through a blood test.
• Hemoglobin electrophoresis identifies abnormal hemoglobin in a laboratory test.
• Genetic testing involves DNA analysis to identify the HBB mutation.

Treatment and Management

• Pain management involves medications to alleviate vaso-occlusive episodes.
• Blood transfusions increase oxygen delivery and reduce anemia.
• Hydroxyurea medication increases production of fetal hemoglobin, reducing sickling.
• Antibiotics prevent and treat infections.
• Bone marrow transplantation is a curative treatment option for some patients.

Complications

• Acute chest syndrome is a life-threatening condition characterized by chest pain, fever, and respiratory distress.
• Stroke is a complication due to blood vessel damage.
• Pulmonary hypertension is increased blood pressure in the lungs, leading to heart failure.
• Kidney disease is a result of chronic kidney damage and failure.

Inheritance and Epidemiology

• SCD is inherited in an autosomal recessive pattern, requiring two copies of the mutated HBB gene.
• SCD is most common in people of African, Mediterranean, and Middle Eastern descent.
• The disease affects approximately 1 in 500 African Americans and 1 in 1,000 Hispanic Americans.

Learn about sickle cell disease, a genetic disorder that affects hemoglobin production, and its causes, including the mutation in the HBB gene and production of abnormal hemoglobin.