CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0426/04262.txt

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$Unique_ID{BRK04262}
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$Title{Thalassemia Major, mediterranean anemia, cooley's anemia}
$Subject{Thalassemia Major Cooley's Anemia Mediterranean Anemia Target Cell
Anemia Beta Thalassemia Major Erythroblastotic Anemia of Childhood Thalassemia
Hereditary Leptocytosis Hemoglobin Lepore Syndromes Microcythemia Thalassemia
Minor Hereditary Spherocytic Hemolytic Anemia Anemias (General) }
$Volume{}
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Copyright (C) 1986, 1987, 1990, 1992, 1993 National Organization for Rare
Disorders, Inc.

71:
Thalassemia Major, mediterranean anemia, cooley's anemia

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

Synonyms

     Cooley's Anemia
     Mediterranean Anemia
     Target Cell Anemia
     Beta Thalassemia Major
     Erythroblastotic Anemia of Childhood
     Thalassemia
     Hereditary Leptocytosis
     Hemoglobin Lepore Syndromes
     Microcythemia

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

     Thalassemia Minor
     Hereditary Spherocytic Hemolytic Anemia
     Anemias (General)

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.


Thalassemia Major is a rare blood disorder characterized by a marked
increase in F hemoglobin and a decrease in the production of certain oxygen
carrying proteins in red blood cells (beta polypeptide chains in the
hemoglobin molecule).  Thalassemia Major is the most severe form of chronic
familial anemias that result from the premature destruction of red blood
cells (hemolytic).  This disease was originally found in people living near
the Mediterranean Sea.  People with this disorder also have a reduced number
of circulating red blood cells (erythrocytes).

Symptoms

The symptoms of Thalassemia Major typically occur very suddenly in infancy or
early childhood.  These may include generalized weakness (malaise), an upset
stomach (dyspepsia), and/or heart palpitations.  Patients may have a yellow
appearance to their skin (jaundice), leg ulcers, an abnormally enlarged liver
(hepatomegaly), an abnormally enlarged spleen (splenomegaly), the presence of
stones in the gall bladder (cholelithiasis), and/or an enlarged abdomen.
Abnormally overactive bone marrow growth may result in a thickened skull
(cranial bones) and prominent cheek bones.

Thalassemia Major can cause the loss of bone (osteoporosis) in the long
bones of the body; fractures are common because bones become fragile.  People
with this disorder may be underdeveloped for their age and short in stature.
Excess iron deposits in the heart muscle can cause heart abnormalities and
eventual cardiac failure.  People with Thalassemia Major may also experience
mental deterioration.  They are prone to repeated infections which can cause
additional problems.

Causes

Thalassemia Major is inherited as an autosomal recessive genetic 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.

The gene that causes Thalassemia Major is located on the short arm of
chromosome 11.

People who have both of the pair of genes (homozygous) that cause
Thalassemia Major have more severe symptoms than those people who have only
one of the pair of genes (heterozygous) that causes the disease.  This
disorder is more common in families who intermarry and in those whose parents
both have a gene for Thalassemia Minor.  (For more information, choose
"Thalassemia Minor" as your search term in the Rare Disease Database.)

Affected Population

Thalassemia Major is a rare disorder that most commonly occurs in people of
Mediterranean heritage, especially Italians and Greeks.  It is also common in
an area that extends from northern Africa and southern Europe to Thailand,
including Iran, Iraq, Indonesia, and southern China.  This disorder affects
males and females in equal numbers.

Related Disorders

Symptoms of the following disorders can be similar to those of Thalassemia
Major.  Comparisons may be useful for a differential diagnosis:

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).

Hereditary Spherocytic Hemolytic Anemia is a rare inherited blood
disorder characterized by the presence of sphere-shaped red blood cells.
These cells have difficulty circulating through the spleen resulting in the
destruction of red blood cells.  The symptoms of Hereditary Spherocytic
Hemolytic Anemia may be present at birth or not be apparent for years, and in
many people the disease may be so mild that it is not diagnosed.  Symptoms
may include fatigue and a yellow (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.  Trauma or
pregnancy may also cause an anemic crisis.  The child may experience fever,
headache, loss of appetite, vomiting, leg sores, and/or general weakness.
(For more information on this disorder, choose "Hereditary Spherocytic
Hemolytic Anemia" as your search term in the Rare Disease Database.)

Other types of anemias include:  Aplastic Anemia; Hereditary Non-
Spherocytic Hemolytic Anemia; Megaloblastic 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 in the Rare Disease Database.)

Therapies:  Standard

A person with Thalassemia Major has severe anemia.  Chronic blood
transfusions may be necessary in severely affected patients to maintain the
levels of hemoglobin in the red blood cells (above 10 gm percent) and to
allow for normal growth.

Without treatment, Thalassemia Major can be life-threatening.  Since iron
overload is a possibility due to repeated blood transfusions, children should
be given as few transfusions as possible.  Daily treatment with the drug
deferroxamine is necessary to avoid severe iron overload.   Removal of the
spleen (splenectomy) may help patients with an abnormally enlarged spleen.
This surgery reduces the number of blood transfusions that may otherwise be
required.

Genetic counseling will be of benefit for patients with Thalassemia Major
and their families.  Genetic tests are available to determine if a person is
a carrier of the gene, and prenatal tests can identify an affected fetus.

Therapies:  Investigational

The orphan drugs arginine butyrate and isobutyramide are being studied as
possible treatments for Thalassemia Major.  Additional study is needed to
determine the long-term safety and effectiveness of these drugs.  For more
information, patients may have their physicians contact:

     Dr. Susan P. Perrine
     Children's Hospital
     Oakland Institute
     747 52nd Street
     Oakland, CA  94609

The orphan drug Sodium Phenylbutyrate is being developed for the
treatment of Thalassemia Major and other diseases that involve the abnormal
formation of red blood cells (sickling diseases).  For more information,
patients may have their physicians contact:

     Saul Brusilow, M.D.
     301 Children's Medical and Surgical Center
     John Hopkins Hospital
     600 North Wolfe Street
     Baltimore, MD  21205
     [phone]

Clinical trials for the treatment of Thalassemia Major are being
conducted on several compounds that bind to iron (chelating agents) for the
treatment of Thalassemia Major.

Bone marrow transplantation is another treatment under investigation for
the treatment of people with Thalassemia Major.  For additional information,
patients may have their physicians contact:

     NIH/National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]

This disease entry is based upon medical information available through
May 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 Thalassemia Major, 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.
     3460 Wilshire Blvd., Suite 1012
     Los Angeles, CA  96010
     [phone]
     [phone]

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

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

For Genetic Information and Genetic Counseling Referrals:

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

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

References

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:  Johns
Hopkins University Press, 1992.  Pp. 1069.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Editors; W.B. Saunders Co., 1990.  Pp. 883-84.

THE MERCK MANUAL, 16th Ed.:  Robert Berkow Ed.; Merck Research
Laboratories, 1992.  Pp. 1172, 1174.

HEMATOLOGY, 4th Ed,:  William J. Williams, et al,; Editors; McGraw-Hill,
Inc., 1990.  Pp. 510-534.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 1658-1661.

MANAGEMENT OF THALASSEMIA MAJOR (COOLEY'S ANEMIA).  S. Piomelli; Hematol
Oncol Clin North Am (Jun 1991; 5(3)).  Pp. 557-69.

BETA-THALASSEMIA MAJOR AND SICKLE CELL DISEASE.  R.B. Butler; NAACOGS Clin
Issu Perinat Womens Health Nurs (1991; 2(3)).  Pp. 349-356.