Genetic Disease Profile:
Sickle Cell Anemia
For more about the
gene that causes sickle cell anemia, see the HBB Gene
Profile. The following was adapted from NIH Publication No. 96-4057.
- Herrick provides the first formal description of sickle cell anemia
when he reports that the blood smear of a dental student at the
Chicago College of Dental Surgery contains "pear-shaped and
- Hahn and Gillespie associate the sickling of red blood cells
with low oxygen conditions.
- Sherman reports that the sickling of red blood cells in the absence
of oxygen is caused by a change in the hemoglobin molecule structure.
- Watson suggests that the presence of fetal hemoglobin in the red
blood cells of sickle cell newborns is the reason they do not show
- Noted physical chemist Linus Pauling and associates publish "Sickle
Cell Anemia, a Molecular Disease" in Science. This paper
explains how protein electrophoresis was used to show that sickle
cell hemoglobin differed in structure from normal hemoglobin. This
was the first time that the cause of a disease was linked to a change
in protein structure.
- Vernon Ingram and J.A. Hunt sequence hemoglobin and discover that
the change of a single amino acid in the protein sequence is the
cause of sickle cell anemia.
- Flavell prepares maps of the human beta and delta globin genes
- Upon the completion of the Multicenter Study of Hydroxyurea in
Sickle Cell Anemia, Charache reports that the anticancer drug hydroxyurea
is the first to reduce the frequent, painful complications that
characterize sickle cell disease .
Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University,
Baltimore, MD. MIM No. 141900 (November 6, 2001) . <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM>
Brief History of Sickle Cell Disease. Joint Center for Sickle Cell
and Thalassemic Disorders. (February 25, 2001). <http://sickle.bwh.harvard.edu/scd_history.htm>
cell anemia is an inherited blood disorder characterized primarily by
chronic anemia and periodic episodes of pain. The underlying problem involves
hemoglobin, a component of red blood cells. Hemoglobin molecules in each
red blood cell carry oxygen from the lungs to body organs and tissues
and bring carbon dioxide back to the lungs.
In sickle cell anemia, the hemoglobin is defective. After hemoglobin molecules
give up their oxygen, some may cluster together and form long, rod-like
structures. These structures cause red blood cells to become stiff and
assume a sickle shape.
Unlike normal red cells, which are usually smooth and donut-shaped, sickled
red cells cannot squeeze through small blood vessels. Instead, they stack
up and cause blockages that deprive organs and tissues of oxygen-carrying
blood. This process produces periodic episodes of pain and ultimately
can damage tissues and vital organs and lead to other serious medical
problems. Normal red blood cells live about 120 days in the bloodstream,
but sickled red cells die after about 10 to 20 days. Because they cannot
be replaced fast enough, the blood is chronically short of red blood cells,
a condition called anemia.
Sickle cell anemia is an autosomal recessive genetic
disorder caused by a defect in the HBB gene, which codes for hemoglobin.
The presence of two defective genes (SS) is needed for sickle cell anemia.
If each parent carries one sickle hemoglobin gene (S) and one normal gene
(A), each child has a 25% chance of inheriting two defective genes and
having sickle cell anemia; a 25% chance of inheriting two normal genes
and not having the disease; and a 50% chance of being an unaffected carrier
like the parents.
Sickle cell anemia affects millions throughout the
world. It is particularly common among people whose ancestors come from
sub-Saharan Africa; Spanish-speaking regions (South America, Cuba, Central
America); Saudi Arabia; India; and Mediterranean countries such as Turkey,
Greece, and Italy. In the Unites States, it affects around 72,000 people,
most of whose ancestors come from Africa. The disease occurs in about
1 in every 500 African-American births and 1 in every 1000 to 1400 Hispanic-American
births. About 2 million Americans, or 1 in 12 African Americans, carry
the sickle cell trait.
The clinical course of sickle cell anemia does not
follow a single pattern; some patients have mild symptoms, and some have
very severe symptoms. The basic problem, however, is the same: the sickle-shaped
red blood cells tend to get stuck in narrow blood vessels, blocking the
flow of blood. This results in the following conditions:
Hand-foot syndrome. When small blood vessels in hands or feet are
blocked, pain and swelling can result, along with fever. This may be the
first symptom of sickle cell anemia in infants.
Fatigue, paleness, and shortness of breath. These are all symptoms
of anemia or a shortage of red blood cells.
Pain that occurs unpredictably in any body organ or joint. A patient
may experience pain wherever sickled blood cells block oxygen flow to
tissues. The frequency and amount of pain vary. Some patients have painful
episodes (also called crises) less than once a year, and some have as
many as 15 or more episodes in a year. Sometimes pain lasts only a few
hours; sometimes it lasts several weeks. For especially severe ongoing
pain, the patient may be hospitalized and treated with painkillers and
intravenous fluids. Pain is the principal symptom of sickle cell anemia
in both children and adults.
Eye problems. The retina, the "film" at the back of the eye that
receives and processes visual images, can deteriorate when it does not
get enough nourishment from circulating red blood cells. Damage to the
retina can be serious enough to cause blindness.
Yellowing of skin and eyes. These are signs of jaundice, resulting
from rapid breakdown of red blood cells.
Delayed growth and puberty in children and often a slight build in
adults. The slow rate of growth is caused by a shortage of red blood
Infections. In general, both
children and adults with sickle cell anemia are more vulnerable to infections
and have a harder time fighting them off. This is the result of spleen
damage from sickled red cells, thus preventing the spleen from destroying
bacteria in the blood. Infants and young children, especially, are susceptible
to bacterial infections that can kill them in as little as 9 hours from
onset of fever. Pneumococcal infections used to be the principal cause
of death in children with sickle cell anemia until physicians began routinely
giving penicillin on a preventive basis to those who are diagnosed at
birth or in early infancy.
Stroke. Defective hemoglobin damages the walls of red blood cells,
causing them to stick to blood vessel walls. The resulting narrowed or
blocked small blood vessels in the brain can lead to serious, life-threatening
strokes, primarily in children.
Acute chest syndrome. Similar to pneumonia, this life-threatening
complication is caused by infection or trapped sickled cells in the lung.
It is characterized by chest pain, fever, and an abnormal chest X ray.
Early diagnosis of sickle cell anemia is critical
so children who have the disease can receive proper treatment.
Blood test - More than 40 states now perform a simple, inexpensive
blood test for sickle cell disease on all newborn infants. This test is
performed at the same time and from the same blood samples as other routine
newborn-screening tests. Hemoglobin electrophoresis is the most widely
used diagnostic test. If the test shows the presence of sickle hemoglobin,
a second blood test is performed to confirm the diagnosis. These tests
also tell whether or not the child carries the sickle cell trait.
Although there is no cure for sickle cell anemia,
doctors can do a great deal to help patients, and treatment is constantly
being improved. Basic treatment of painful crises relies heavily on painkilling
drugs and oral and intravenous fluids to reduce pain and prevent complications.
Blood Transfusions - Transfusions correct anemia by increasing
the number of normal red blood cells in circulation. They can also be
used to treat spleen enlargement in children before the condition becomes
life-threatening. Regular transfusion therapy can help prevent recurring
strokes in children at high risk.
Oral Antibiotics - Giving oral penicillin twice a day beginning
at 2 months and continuing until the child is at least 5 years old can
prevent pneumococcal infection and early death. Recently, however, several
new penicillin-resistant strains of pneumonia bacteria have been reported.
Since vaccines for these bacteria are ineffective in young children, studies
are being planned to test new vaccines.
Hydroxyurea - The first effective drug treatment for adults with
severe sickle cell anemia was reported in early 1995, when a study conducted
by the National Heart, Lung, and Blood Institute showed that daily doses
of the anticancer drug hydroxyurea reduced the frequency of painful crises
and acute chest syndrome. Patients taking the drug needed fewer blood
Regular health maintenance is critical for people with sickle cell anemia.
Proper nutrition, good hygiene, bed rest, protection against infections,
and avoidance of other stresses all are important in maintaining good
health and preventing complications. Regular visits to a physician or
clinic that provides comprehensive care are necessary to identify early
changes in the patient's health and ensure immediate treatment.
Today, with good health care, many people with sickle cell anemia are
in reasonably good health much of the time and living productive lives.
In fact, in the past 30 years, the life expectancy of people with sickle
cell anemia has increased.
and Support Groups
Cell Disease Association of America (SCDAA)
Sickle Cell Association
Heart, Lung, and Blood Institute
Sickle Cell Information Center
Center for Sickle Cell and Thalassemic Disorders
Electrophoresis and Sickle
Cell Test - Entries in ADAM
Medical Encyclopedia available through MEDLINEplus
Cell Test - Description of the test provided by Lab
Tests Online, a peer-reviewed, non-commercial resource on clinical
Cell Anemia Studies at ClinicalTrials.gov
Other Sickle Cell
Entry for Sickle Cell Anemia
Genes and Disease: Sickle Cell Anemia
Cell Anemia from New York Online Access to Health (NOAH)
Cell Disease Information from the March of Dimes
Publication No. 02-2117: The Management of Sickle Cell Disease
(206 page document that you can download or view online as PDF. Printed
version also can be ordered.)
S Allele and Sickle Cell Disease - This HuGE Review is a peer-reviewed
publication from the Human Genome Epidemiology Network (HuGENet) at
the CDC's Office of Genetics and Disease Prevention. It describes the
gene, genetic variants, associated disorders, interactions, as well
as laboratory and population testing.