Meaning of sickle cell disease: One letter changed in a hemoglobin gene is enough to stiffen red cells into crescents that jam small vessels and break up early.

Definition of sickle cell disease

Sickle cell disease is an inherited blood disorder caused by an altered gene for hemoglobin, the oxygen carrying protein inside red blood cells. The abnormal hemoglobin sticks together when oxygen levels fall, forcing normally soft disc shaped cells into rigid crescents. Those cells block small blood vessels and break apart early, producing episodes of pain and a lasting anemia.

What does the sickle gene actually change?

A single change in the gene for the beta globin chain swaps one building block of the protein for another. The result, hemoglobin S, works normally while it is carrying oxygen. Once it gives that oxygen up it links into long stiff fibers that distort the cell from the inside. Early on a cell can recover its shape after picking up oxygen again, but repeated cycles damage the membrane until the change becomes permanent. Cold, dehydration, infection and low oxygen all make sickling more likely.

Why does it cause both pain and anemia?

Two separate problems follow from the same distorted cell. Rigid cells snag in small vessels and cut off blood supply to the tissue beyond, and the resulting episode of pain in bones, chest or abdomen is the most familiar feature of the disease. Over years the same blockages injure the spleen, kidneys, lungs, eyes, hips and brain. Separately, sickled cells survive a fraction of the normal red cell lifespan, so the marrow cannot keep pace and a lasting anemia develops, along with jaundice from the pigment released as cells break down.

How do disease and trait differ?

FeatureSickle cell diseaseSickle cell trait
Genes inheritedTwo altered beta globin genes, at least one of them sickleOne sickle gene alongside one normal gene
Red cellsSickle under everyday conditionsKeep their shape except under extreme stress
EffectPain episodes, anemia, organ damage over timeUsually no symptoms at all
Passing it onEvery child inherits a sickle geneOn average half of children inherit it

Sickle cell anemia is often used as though it meant the same thing, but strictly it names the form in which both beta globin genes carry the sickle change. Sickle cell disease is the wider label, covering that form along with combinations of the sickle gene and a different abnormal beta globin gene, such as hemoglobin C or beta thalassemia, which behave similarly but not identically. The condition is most common in people of West and Central African descent and also occurs in Mediterranean, Middle Eastern, Indian and Caribbean populations, a distribution that follows historic malaria exposure, since carrying a single sickle gene offers some protection against severe malaria.

Also known as

sickle cell anemia

Used in a sentence

Genetic counseling was offered to the family after newborn screening identified sickle cell disease.

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Good to know

Sickle cell disease requires two altered beta globin genes, at least one of them the sickle gene, while sickle cell trait means a single sickle gene alongside a normal one and usually causes no symptoms, although it can still be passed to a child.

For learning, not diagnosis. This glossary provides general educational information and is not a substitute for advice from a qualified healthcare professional. If you may be experiencing a medical emergency, contact local emergency services.