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Beta-thalassemia (BT) is characterized by deficiency (Beta+) or absence (Beta0) of synthesis of the beta globin chains of hemoglobin (Hb).
ORPHA:848Classification level: Disorder
Exact prevalence is unknown but annual incidence at birth of symptomatic BT is estimated at 1/100,000 worldwide. The disease was initially described in the Mediterranean basin but severe forms of BT frequently occur throughout the Middle East, South East Asia, India and China. Population migrations have lead to global distribution of the disease.
Three main types of BT have been described (minor, intermedia and major; see these terms). 1) Thalassemia minor (BT-minor, BT trait) is the heterozygous form and is usually asymptomatic. 2) Thalassemia major (Cooley anemia; BT-major) is the homozygous form and associates splenomegaly and microcytic and hypochromic anemia resulting from dyserythropoiesis and hemolysis. Onset generally occurs from 6-24 months of age. The severe anemia requires systematic transfusions to maintain Hb levels above the range of 90-100 g/L and to allow normal activity. Long-term transfusion of red cell concentrates results in iron overload which hampers the vital prognosis (mainly due to cardiac involvement) and causes significant morbidity (due to endocrinal and hepatic iron deposition). 3) Thalassemia intermedia (BTI) in which the anemia is less severe and diagnosed later in life compared to BT-major. Patients with BTI may or may not require occasional transfusions. Hypersplenism, cholelithiasis, extramedullary hematopoiesis, thrombotic complications and progressive iron overload are the main clinical features that may complicate the course of BTI. Other forms include BT associated with Hb anomalies (HbE - beta-thalassemia resulting in BTI or less frequently BT-major, HbC - beta-thalassemia, delta-beta-thalassemia and hereditary persistence of fetal Hb with BT resulting in inconstant manifestations of BTI; see these terms). Rare autosomal dominant forms have also been described (dominant beta-thalassemia; see this term). In rare instances, BT trait is associated with trichothiodystrophy or X-linked thrombocytopenia (see these terms).
Diagnosis of BT anemia relies on analysis of Hb by electrophoresis or HPLC. In BT-major, HbA is absent or greatly reduced and HbF predominates. In BT-minor, the levels of HbA2 are increased and the levels Hb are usually normal to low with microcytosis and hypochromia.
Transmission is autosomal recessive and around 200 mutations (B0 or B+) have been identified. Genetic counseling is recommended to permit couples who are at risk an informed choice among available options including prenatal diagnosis.
Management and treatment
There are two major treatment options for BT. 1) A combination of regular transfusions and iron chelation therapy with early and regular parenteral deferoxamine administration has led to increased survival during the last 40 years. Availability of new oral iron chelators and monitoring of cardiac iron overload by MRI result in further clinical improvement and current evaluation is ongoing to determine their impact on morbidity and mortality. In 2006, deferasirox, a once-daily orally administered iron chelator, obtained EU marketing authorization as an Orphan drug for first-line treatment of BT-related iron overload. The marketing authorization for deferiprone, another orally active iron chelator, particularly effective in removing heart iron, is restricted to cases in which treatment with deferoxamine fails or is contraindicated. 2) Hematopoietic stem cell transplant is the curative treatment for BT major: results are very favorable for children displaying an HLA-identical familial donor. Recently, a first patient was successfully treated with gene therapy.
Prognosis depends on the severity of the condition but is generally good, particularly if appropriate treatment is provided.