Thalassemia Major

Thalassemia Major

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Thalassemia Major is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

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

Disorder Subdivisions

  • None

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.

Symptoms

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.

Causes

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.

Standard Therapies

Diagnosis

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.



Treatment

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:

www.centerwatch.com



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:



(617)252-7500

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.

References

TEXTBOOKS

Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:877-79.



Fauci AS, et al, eds. Harrison's Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:651.



Stein JH, et al, eds. Internal Medicine, 4th Ed. Mosby-Year Book, Inc., 1994:854-57.



Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:881-83.



JOURNAL ARTICLES

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.



FROM THE INTERNET

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

Resources

March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



Cooley's Anemia Foundation, Inc.

330 7th Ave

Suite 900

New York, NY 10001

USA

Tel: (212)279-8090

Fax: (212)279-5999

Tel: (800)522-7222

Email: info@cooleysanemia.org

Internet: http://www.cooleysanemia.org



Sickle Cell Disease Association of America, Inc.

231 East Baltimore Street

Suite 800

Baltimore, MD 21202

USA

Tel: (410)528-1555

Fax: (410)528-1495

Tel: (800)421-8453

Email: scdaa@sicklecelldisease.org

Internet: http://www.sicklecelldisease.org



NIH/National Heart, Lung and Blood Institute

P.O. Box 30105

Bethesda, MD 20892-0105

Tel: (301)592-8573

Fax: (301)251-1223

Email: nhlbiinfo@rover.nhlbi.nih.gov

Internet: http://www.nhlbi.nih.gov/



Children's Cancer & Blood Foundation

333 East 38th Street, Suite 830

New York, NY 10016-2745

Tel: (212)297-4336

Fax: (212)297-4340

Email: info@childrenscbf.org

Internet: http://www.childrenscbf.org/



Cochrane Cystic Fibrosis and Genetic Disorders Group

Institute of Child Health, University of Liverpool

Alder Hey Children's NHS Foundation Trust

Liverpool, L12 2 AP

United Kingdom

Tel: 441512525696

Email: nikkij@liverpool.ac.uk

Internet: http://cfgd.cochrane.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Sickle Cell Disease Foundation of California

5777 W. Century Blvd., Suite 1230

Los Angeles, CA 90045

Tel: (310)693-0247

Fax: (310)216-0307

Tel: (877)288-2873

Email: info@scdfc.org

Internet: http://www.scdfc.org



Thalassemia Support Foundation

PO Box 26398

Santa Ana, CA 92799

Email: tsf@helpthals.org

Internet: http://www.helpthals.org



For a Complete Report

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