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$Unique_ID{BRK04221}
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$Title{Sickle Cell Disease}
$Subject{Sickle Cell Disease Sickle Cell Anemia Sickle Cell Trait Sickle
Cell-Hemoglobin C Disease Sickle Cell-Hemoglobin D Disease Sickle
Cell-Thalassemia Disease Hereditary Spherocytic Hemolytic Anemia Thalassemia
Major (Cooley's Anemia) Thalassemia Minor }
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Copyright (C) 1984, 1985, 1987, 1989, 1990, 1992, 1993 National
Organization for Rare Disorders, Inc.

25:
Sickle Cell Disease

** IMPORTANT **
It is possible that the main title of the article (Sickle Cell Disease)
is not the name you expected.  Please check the SYNONYMS listing to find the
alternate name and disorder subdivisions covered by this article.

Synonyms

     Sickle Cell Anemia
     Sickle Cell Trait

DISORDER SUBDIVISIONS:

     Sickle Cell-Hemoglobin C Disease
     Sickle Cell-Hemoglobin D Disease
     Sickle Cell-Thalassemia Disease

Information on the following diseases can be found in the Related
Disorders section of this report:

     Hereditary Spherocytic Hemolytic Anemia
     Thalassemia Major (Cooley's Anemia)
     Thalassemia Minor

General Discussion

** REMINDER **
The Information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.


Sickle Cell Disease is a rare inherited blood disorder.  It is
characterized by the presence of sickle or crescent shaped red blood cells
(erythrocytes) in the bloodstream.  These abnormally shaped cells become
rigid and lodge themselves in the very tiny blood vessels (capillaries) of
the peripheral blood system (blood vessels outside of the heart).  The
capillaries become clogged, preventing the normal flow of oxygen to tissues.
Sickle Cell Disease has several recognized forms including Sickle Cell
Anemia, Sickle Cell Hemoglobin C Disease and Sickle Cell Thalassemia Disease.

Symptoms

Symptoms of Sickle Cell Disease develop due to the low level of hemoglobin in
the red blood cells (erythrocytes) and a resulting inability of the blood to
supply oxygen to the tissues of the body.  Sickle Cell Disease is
characterized by sudden acute attacks of pain particularly in the chest,
painful inflammation of the fingers or toes (sickle cell dactylitis), a
lingering upper respiratory infection and/or a pale color of the tongue and
lips.  Other symptoms may include:  irritability; crying; poor eating habits;
an enlarged spleen (splenomegaly); an enlarged liver (hepatomegaly); yellow
color to the skin (jaundice); stroke; a yellow appearance of the eyeballs
(scleral icterus); and/or heart murmurs.

The symptoms of Sickle Cell Disease typically begin in the first 3 years
of life.  In children ages 3 to 5, the signs of the disease are often pain in
the chest, abdomen, limbs and joints.  Joint pain generally follows exposure
to cold, overexertion, infection and/or dehydration.  Joint pain is usually
not accompanied by joint swelling.  Children with Sickle Cell Disease may
grow slowly and have many nosebleeds.

In adolescents and young adults the symptoms of Sickle Cell Disease may
include severe joint pain, delayed puberty, progressive anemia, leg sores,
nosebleeds and/or dental disease.   Kidney disease and a scarring of retinal
tissues of the eyes may also occur.  Occasionally Sickle Cell Disease may
cause a loss of bone, particularly the top of the thigh bone (osteonecrosis
of the femoral head).  The loss of bone may cause pain in the joints when
walking, standing and/or lifting.  Cardiac symptoms may also occur in people
with Sickle Cell Disease including a rapid heart beat (tachycardia), heart
murmurs and/or other heart problems.

Sickle Cell Disease may also appear in people over 20 years of age.  When
Sickle Cell Disease occurs in adulthood people generally experience pain in
the chest, abdomen, limbs and/or joints.  These painful episodes may become
less frequent with advancing age.  Leg sores, inflammation of the retina
(retinitis) of the eyes, and gallbladder disease are often present.

Both Sickle Cell-Thalassemia Disease and Sickle Cell-Hemoglobin C Disease
are milder forms of Sickle Cell Disease.  The symptoms of Hemoglobin C
Disease occur later in life than those of Sickle Cell Disease.

Causes

Sickle Cell Disease is a rare blood disorder that is inherited as an
autosomal recessive trait.  Human traits, including the classic genetic
diseases, are the product of the interaction of two genes, one received from
the father and one from the mother.  In recessive disorders, the condition
does not appear unless a person inherits the same defective gene for the same
trait from each parent.  If one receives one normal gene and one gene for the
disease, the person will be a carrier for the disease, but usually will not
show symptoms.  The risk of transmitting the disease to the children of a
couple, both of whom are carriers for a recessive disorder, is twenty-five
percent.  Fifty percent of their children will be carriers, but healthy as
described above.  Twenty-five percent of their children will receive both
normal genes, one from each parent, and will be genetically normal.

People who inherit only one sickle cell gene are said to have "sickle
cell trait" and are generally symptom free carriers who can pass the gene on
to their offspring.  However, people with Sickle Cell Disease must inherit
two genes for sickle cell (one from each parent) in order to get the disease.

Affected Population

Sickle Cell Disease affects 0.6 percent of the African American population in
the United States (approximately 50,000 cases in the United States).  The
sickle cell trait is present in approximately 40 percent of the general
population in some areas of Africa.  The incidence of sickle cell trait in
Americans of African descent is 9 percent.   Americans whose ancestry is
Asiatic Indian, Italian, Greek or Mediterranean may also be affected by
Sickle Cell Disease.

Related Disorders

Symptoms of the following disorders can be similar to those of Sickle Cell
Disease.  Comparisons may be useful for a differential diagnosis:

Hereditary Spherocytic Hemolytic Anemia is a rare inherited disorder of
the blood that causes the red blood cells to become sphere-shaped making it
difficult for them to circulate through the spleen.   This causes excessive
red blood cell destruction.  The symptoms of Hereditary Spherocytic Hemolytic
Anemia may be present at birth or not be apparent for years.  In many people
the symptoms are so mild that the disease is not recognized.   Symptoms may
include fatigue and a yellow or jaundice appearance to the skin.  Generally
the spleen is enlarged resulting in abdominal discomfort.  An infection is
the most common trigger of an anemic crisis (dangerously low levels of red
blood cells in the blood).  Trauma or pregnancy may worsen the anemic crisis.
The child may experience fever, headache, loss of appetite, vomiting, leg
sores, and general weakness.  Some children experience nosebleeds.  (For more
information on this disorder, choose "Hereditary Spherocytic Hemolytic
Anemia" as your search term in the Rare Disease Database.)

Thalassemia Major (Cooley's Anemia or Mediterranean Anemia) is
characterized by a marked increase in F hemoglobin, a decrease of proteins
within hemoglobin and an abnormally low level of red blood cells.
Thalassemia Major is the most severe form of chronic familial hemolytic
anemias and is primarily in people with Mediterranean ancestry.  The onset of
symptoms is usually rapid and may occur during infancy or early childhood.
Symptoms may include generalized weakness, overall feeling of illness
(malaise), an upset stomach (dyspepsia), heart palpitations, a yellow color
to the skin (jaundice) and/or leg sores.  Other symptoms may include an
enlarged liver (hepatomegaly), an enlarged spleen (splenomegaly),
inflammation of the gall bladder (cholelithiasis), and/or an enlarged
abdomen.  Children with Thalassemia Major may have heart problems and they
may be short for their age due to bone problems.  (For more information on
this disorder, choose "Thalassemia Major" as your search term in the Rare
Disease Database).

Thalassemia Minor is a relatively mild form of anemia that is typically
present at birth.  It is inherited as an autosomal recessive genetic trait.
Constant fatigue may be the only symptom of this disorder.  However, if
anemia becomes severe, the spleen may become slightly enlarged
(splenomegaly) and there may be a pale color to the skin.  Occasionally a
child with Thalassemia Minor may complain of pain in the left upper side of
the abdomen.  This disorder may be aggravated by stress, infections,
malnutrition, and/or pregnancy.   (For more information on this disorder,
choose "Thalassemia Minor" as your search term in the Rare Disease Database).

Other types of anemias include:  Aplastic Anemia; Hereditary Non-
Spherocytic Hemolytic Anemia; Megablastic Anemia; Warm Antibody Hemolytic
Anemia; Cold Antibody Hemolytic Anemia; Acquired Autoimmune Hemolytic Anemia;
Pernicious Anemia; Folic Acid Deficiency Anemia; Blackfan-Diamond Anemia; and
Fanconi's Anemia.  For information on other types of Anemias, choose "Anemia"
as your search term on the Rare Disease Database.

Therapies:  Standard

The treatment of Sickle Cell Disease is symptomatic and supportive.  People
with Sickle Cell Disease must get regular medical checkups, avoid chills,
dress warmly, eat nutritionally balanced meals, get adequate sleep, avoid
standing in the cold without exercising, and practice deep breathing for 5
minutes before going to sleep.  Vaccination against pneumococcal infections
may be given to children over the age of 2 years.

There are two tests that are used to screen for Sickle Cell Disease.
Umbilical cord blood screening is used to detect Sickle Cell Disease in
newborns.  Hemoglobin testing (electrophoresis) can detect the major
varieties of Sickle Cell Disease.

Genetic counseling will be of benefit for patients and their families.
Genetic testing can determine if a person is carrying the Sickle Cell trait.
In general if a couple both have the Sickle Cell trait they have a 25 percent
chance of having a child with Sickle Cell Disease.

Therapies:  Investigational

Research is ongoing into ways of increasing the levels of fetal hemoglobin in
people with Sickle Cell Disease.  One drug being tested is Hydroxyurea (trade
name Hydrea), which is ordinarily used to treat leukemia.  This drug is
manufactured by Bristol-Myers Squibb Co., Evansville, IN.

The flavor enhancer butyrate (a natural fatty acid) is currently being
tested for treatment of Sickle Cell disease.  Researchers have found that
when injected into the bloodstream, butyrate turns on a gene that typically
shuts down before birth.  Butyrate is a natural substance that when eaten has
no effect but when injected achieves an increase in healthy levels of
hemoglobin.  More research is needed to prove the effectiveness of this
treatment.

Researchers are also investigating danazol for use as a treatment for
Sickle Cell Disease.  This drug is a gonadotropin secretion inhibitor that
may make sickle cell erythrocytes more flexible and better able to flow
through very small capillaries.  This drug is being tested by Dr. William
Harrington of the University of Miami School of Medicine.  Research is in
preliminary stages and extensive investigations are needed to determine
safety and effectiveness.

Poloxamer 188, N.F. (RheothRx Copolymer) is a new orphan drug being
investigated as a treatment for acute episodes of pain due to Sickle Cell
Disease (sickle cell anemia crisis).  Poloxamer 188, N.F. is manufactured by:

     CytRx Corp.
     150 Technology Parkway
     Technology Park/Atlanta
     Norcross, GA 30092

Studies are being conducted on the use of immunoglobulin (Sandoglobulin)
as a possible treatment for Sickle Cell Disease.  The safety and
effectiveness of this treatment are not yet known.

The orphan drug OM 491 (Drepanol) is being tested as a treatment for
Sickle Cell Disease.  It is sponsored by:

     Omex International, Inc.
     6001 Savoy, Suite 110
     Houston, TX, 77036

Clinical trials are underway to study the drug combination of
Erythropoietin (EPO) and Hydroxyurea in Sickle Cell Anemia.  Interested
persons may wish to have their physician contact:

     Samuel Carache
     Johns Hopkins Hospital
     600 N. Wolfe St.
     Baltimore, MD  21205
     [phone]

This disease entry is based upon medical information available through
February 1993.  Since NORD's resources are limited, it is not possible to
keep every entry in the Rare Disease Database completely current and
accurate.  Please check with the agencies listed in the Resources section for
the most current information about this disorder.

     Resources

For more information on Sickle Cell Disease, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     National Association for Sickle Cell Disease, Inc.
     3345 Wilshire Blvd., Suite 1106
     Los Angeles, CA  96010
     [phone]
     [phone]

     NIH/National Heart, Lung and Blood Institute (NHLBI)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]

     Cooley's Anemia Foundation, Inc.
     105 East 22nd St.
     New York, NY  10010
     [phone]
     [phone] (New York state)
     [phone] (all other states)

     The Canadian Sickle Cell Society
     1076 Bathurst Street, Suite 305
     Toronto, Ontario M5R 3G9
     Canada

For Genetic Information and Genetic Counseling Referrals:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY 10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

References

CECIL TEXTBOOK OF MEDICINE, 18th ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Eds.:  W. B. Saunders Co., 1988.  Pp. 149, 152, 936-42.

THE MERCK MANUAL 15th ed:  R. Berkow, et al:  eds; Merck, Sharp & Dohme
Research Laboratories, 1987.  Pp. 1120.

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:
Johns Hopkins University Press, 1992.  Pp. 481-483.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Editors; W.B. Saunders Co., 1990.  Pp. 888-893.

HEMATOLOGY, 4th Ed.:  William J. Williams, et al,; Editors; McGraw-Hill,
Inc., 1990.  Pp. 614-625.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 1658-1660.

Research Resources Reporter, National Institutes of Health, June 1991.
Pp. 10-11.

MANAGEMENT OF PATIENTS WITH SICKLE CELL DISEASE, R. Steingart; Med Clin
North Am (May 1992; 76(3)):  Pp.669-680.

SICKLE CELL ANEMIA AND MAJOR ORGAN FAILURE, D.R. Powers; Hemoglobin
(1990; 14(6)):  Pp. 573-598.