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Beta-Thalassemia.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.
2000 Sep 28 [updated 2013 Jan 24].

Excerpt

DISEASE CHARACTERISTICS:

Beta-thalassemia (β-thalassemia) is characterized by reduced synthesis of the hemoglobin subunit beta (hemoglobin beta chain) that results in microcytic hypochromic anemia, an abnormal peripheral blood smear with nucleated red blood cells, and reduced amounts of hemoglobin A (HbA) on hemoglobin analysis. Individuals with thalassemia major have severe anemia and hepatosplenomegaly; they usually come to medical attention within the first two years of life. Without treatment, affected children have severe failure to thrive and shortened life expectancy. Treatment with a regular transfusion program and chelation therapy, aimed at reducing transfusion iron overload, allows for normal growth and development and may improve the overall prognosis. Individuals with thalassemia intermedia present later and have milder anemia that only rarely requires transfusion. These individuals are at risk for iron overload secondary to increased intestinal absorption of iron as a result of ineffective erythropoiesis.

DIAGNOSIS/TESTING:

The diagnosis of β-thalassemia relies on measuring red blood cell indices that reveal microcytic hypochromic anemia, nucleated red blood cells on peripheral blood smear, hemoglobin analysis that reveals decreased amounts of HbA and increased amounts of hemoglobin F (HbF) after age 12 months, and the clinical severity of anemia. Molecular genetic testing of HBB, the gene encoding the hemoglobin subunit beta, may be useful for predicting the clinical phenotype in some cases as well as presymptomatic diagnosis of at-risk family members and prenatal diagnosis.

MANAGEMENT:

Treatment of manifestations: Thalassemia major: Regular transfusions correct the anemia, suppress erythropoiesis, and inhibit increased gastrointestinal absorption of iron. The only available definitive cure is bone marrow transplantation from a matched family or unrelated donor or cord blood transplantation from a related donor. Thalassemia intermedia: symptomatic therapy based on splenectomy in most affected individuals, sporadic red cell transfusions in some, and folic acid supplementation. Prevention of primary manifestations: See Treatment of manifestations. Prevention of secondary complications: Prevention of transfusional iron overload by adequate iron chelation. Surveillance: Thalassemia major: Monitoring of the effectiveness/side effects of transfusion therapy and chelation therapy in patients of all ages by monthly physical examination; bimonthly assessment of liver function tests; every three month determination of serum ferritin concentration; every six month evaluation of growth and development (during childhood); and annual evaluation of eyes, hearing, heart, endocrine function (thyroid, endocrine pancreas, parathyroid, adrenal, pituitary), and liver (ultrasound examination). In adults: bone densitometry to assess for osteoporosis; serum alpha-fetoprotein concentration for early detection of hepatocarcinoma in those with hepatitis C and iron overload; regular gallbladder echography for early detection of cholelithiasis for those at risk. Agents/circumstances to avoid: Alcohol consumption, iron-containing preparations. Evaluation of relatives at risk: If prenatal diagnosis has not been used and if the pathogenic allelic variants have been identified in an affected family member, molecular genetic testing of at-risk sibs should be offered to allow for early diagnosis and appropriate treatment.

GENETIC COUNSELING:

The β-thalassemias are inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Heterozygotes may be slightly anemic but are clinically asymptomatic. Carriers are often referred to as having thalassemia minor (or β-thalassemia minor). Carrier testing for individuals at risk (including family members, gamete donors, and members of at-risk populations) is possible. Prenatal testing for pregnancies at increased risk is possible if the pathogenic allelic variants in the family are known.

Copyright © 1993-2014, University of Washington, Seattle. All rights reserved.

PMID:
20301599
[PubMed]
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