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Thalassemia Major

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Synonyms of Thalassemia Major

Disorder Subdivisions

General Discussion

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 anemia that results 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). Thalassemia major is inherited as an autosomal recessive trait.


Newborns with thalassemia major are often have no symptoms at birth. Symptoms typically appear suddenly during the first few months of infancy or, in rare cases, early childhood. These symptoms may include a general feeling of ill health (malaise), weakness, pale complexion, upset stomach (dyspepsia), and/or heart palpitations. Affected infants may have a yellow appearance to their skin, eyes, and mucous membranes (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 abnormally prominent cheekbones.

Thalassemia major can cause the loss of bone mass (osteoporosis) in the long bones of the body, resulting in brittle bones that are prone to fractures. People with this disorder may be underdeveloped for their age and short in stature. Excessive iron deposits in the heart muscle can cause heart abnormalities and eventual cardiac failure. People with thalassemia major may also experience mental deterioration. Affected individuals are prone to repeated infections that may cause additional problems.


Thalassemia major 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 an individual 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 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

The gene that causes thalassemia major is located on the short arm of chromosome 11 (11p.15.5). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q." Chromosomes are further subdivided into bands that are numbered. For example, "chromosome 11p15.5" refers to band 15.5 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 Populations

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.)

Standard Therapies

A diagnosis of thalassemia major is made based upon a detailed patient history, a thorough clinical evaluation, identification of characteristics findings, and blood tests or a test known as electrophoresis. In many cases, state screening will identify newborns with the disorder. A diagnosis may be confirmed by testing an affected child's parents for the presence of the thalassemia major trait.

Individuals with thalassemia major have a severe reduction in circulating red blood cells (severe anemia). Chronic blood transfusions may be necessary in severely affected individuals to maintain the levels of hemoglobin in the red blood cells (above 10 gm percent) and to allow for normal growth.

In 2005, the orphan drug desferasirox (Exjade) was approved by the FDA for marketing for the treatment of thalassemia major. This drug is sponsored by:

Novartis Pharmaceuticals Corporation
One Health Plaza,
East Hanover, 07936-1080

Without treatment, thalassemia major may progress to a life-threatening condition. 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 affected individuals 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 individuals with thalassemia major and their families. Genetic tests are available to determine whether a person is a carrier of the gene, and prenatal tests can identify an affected fetus. Additional treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

As of January 2005, there were five clinical trials related to thalassemia major on the NIH website.

Bone marrow transplantation is one treatment approach under investigation for the treatment of people with thalassemia major. For additional information, patients may have their physicians contact:

Fairview University Medical Center
Minnieapolis, MN 55455
Phone: Lakshmanan Krishnamurti (recruiting) (612) 626-2778

Clinical trials are being conducted on several compounds that bind to iron (chelating agents) for the treatment of thalassemia major. Biomedical Frontiers, Inc., is studying an orphan drug known as 40SD02 as a possible treatment for thalassemia. This is an injectable iron-binding drug. Further information can be obtained by contacting the Minneapolis-based company at:

Biomedical Frontiers, Inc.
1095 Tenth Ave. SE
Minneapolis, MN 55414
Tel.: (612) 378-0228
Fax: (612) 378-3601

Genzyme Corporation is comparing the safety and iron excretion properties of desferoxamine (DFO) and GT56-252, an experimental oral iron chelator. Further information can be obtained by contacting Genzyme at:

Website: www.genzyme.com

The Office of Orphan Products Development at the U.S. Food and Drug Administration is sponsoring a study of L-glutamine therapy for sickle cell anemia or thalassemia. This is an amino acid that has been wiely used for other purposes. For information, contact Yutaka Niihara, MD, at Harbor-UCLA Research and Education Institute in Torrance, California, at (9310) 222-3695 or ysniihara@aol.com.

Some studies have shown that the drug hydroxyurea may be helpful for the treatment of thalassemia major. More studies are needed to determine the long-term safety and effectiveness of this treatment.

Thalassemia Major Resources



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Angelucci E, et al. Hepatic iron concentration and total body iron stores in thalassemia major. N Engl J Med. 2000;343:327-31.

Olivieri N, et al. The beta-thalassemias. N Engl J Med. 1999; 341:99-109.

Taher A, et al. Efficacy and side effects of deferiprone (L1) in thalassemia patients not compliant with desferrioxamine. Acta Haematol. 1999;101:173-77.

Barman Balfour JA, et al. Deferiprone: a review of its clinical potential in iron overload in beta-thalassemia major and other transfusion-dependent diseases. Drugs. 1999;58:553-78.

Arruda VR, et al. Successful use of hydroxurea in beta-thalassemia major. N Engl J Med. 1997;336:964.

Olivieri N, et al. Iron-chelation therapy with oral deferiprone in patients with thalassemia major. N Engl J Med. 1995;332:918- 22.

Mehta J, et al. Deferiprone in iron overload. N Engl J Med. 1995;333:597-99.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 141900; Last Update: 7/13/99.

Report last updated: 2008/04/20 00:00:00 GMT+0