Sickle-Cell Disease Overview

Introduction

• Cells can have various shapes: squishy cylinders, jagged zig-zags.
• Small changes at the microscopic level can lead to significant consequences.
• This lecture focuses on sickle-cell disease and its effects on red blood cells.

Red Blood Cells and Hemoglobin

• Red blood cells transport oxygen from lungs to body tissues.
• Filled with hemoglobin proteins that carry oxygen molecules.
• Normal shape: pliable, doughnut-like, allowing flexibility in tiny blood vessels.

Mutation in Sickle-Cell Disease

• A single genetic mutation alters hemoglobin structure.
• After releasing oxygen, mutated hemoglobin proteins lock together in rigid rows.
• This causes red blood cells to deform into a sickle shape.

Effects of Sickled Cells

• Sickled cells are harder and stickier, hindering smooth flow through blood vessels.
• Can clog vessels, preventing oxygen from reaching tissues.
• Symptoms appear from less than a year old, including:
  • Stabbing pain in oxygen-deprived tissues.
  • Specific symptoms depend on the location of vessel blockage:
    • Spleen blockage: risk of dangerous infections.
    • Lung blockage: fever and breathing difficulties.
    • Eye blockage: vision problems and retinal detachment.
    • Brain blockage: risk of stroke.
• Sickled red blood cells have a lifespan of 10-20 days, unlike healthy cells that last about 4 months.
• Results in sickle-cell anemia due to constantly depleted red blood cell supply.

Evolutionary Background

• Sickle cell mutation evolved as a beneficial adaptation.
• Traced to regions affected by malaria, a tropical disease spread by mosquitoes.
• Malaria uses red blood cells as hosts, but sickle-shaped cells offer resistance to the disease.
• Inheriting one mutation: life difficulty for malaria, with most red blood cells remaining healthy.
• Inheriting the mutation from both parents leads to sickle-cell anemia.
• Most individuals with sickle-cell disease have ancestry linked to malaria-endemic countries.

Current Treatments

• Hydroxyurea was the only medication for years to reduce sickling and improve life expectancy.
• Bone marrow transplantations can be curative but are complex and often inaccessible.
• New medications are emerging:
  • Keeping oxygen bonded to hemoglobin to prevent sickling.
  • Reducing sickled cells' stickiness.
• Advances in DNA editing potentially allow stem cells to produce normal hemoglobin.
• Improving treatment availability in malaria-affected areas can enhance patients' quality of life.