Jewish Genetic Disease Consortium

Affected Jewish population(s):
Sephardic and Mizrahi Jews.

Carrier frequency in affected Jewish population(s):
From 1 in 5 to 1 in 7.

Presence in other population groups:
Increased frequency in Cypriot, Sardinian, Italian, Middle Eastern, Southeast Asian, East Asian, Indian populations. Frequency varies according to ethnic background.

Symptoms:
Beta-Thalassemia Major: Children develop life-threatening anemia, failure to gain weight or grow at a normal rate, and yellowing of the skin and whites of the eyes. Individuals may have an enlarged spleen, liver and heart and their bones may become misshapen. Adolescents with this disorder may experience delayed puberty. Often people with Thalassemia Major require frequent blood transfusions to replenish red blood cells. Treatment often allows for normal growth and development, although a build-up of iron in the blood may require chelation therapy.
Beta-Thalassemia Intermedia: Mild to moderate anemia, as well as slow growth and bone abnormalities that present later than Thalassemia Major and rarely require transfusions.
Beta-Thalassemia Minor: No symptoms.

Age of onset of symptoms:
Within the first 2 years of life for Thalassemia Major. Early childhood or later in life for Thalassemia Intermedia.

Impact on lifespan:
Lifespan of individuals with Beta-Thalassemia Major is dependent on how they respond to long-term treatment programs. Treatment often extends life expectancy into the 20s to 40s. Lifespan for individuals with Beta-Thalassemia Intermedia and Minor is normal.

What causes the disease:
Mutations in the gene called HBB cause a reduction in the production of the beta-globin chain of hemoglobin, reducing the overall amount of hemoglobin and increasing toxic amounts of alpha-globin chains.

Treatment or management:
People with Thalassemia Major require lifelong blood transfusions. This can cause an overload of iron which in turn requires chelation therapy. Bone marrow transplantation has been successful in some.

Carrier screening – number of mutations screened for and detection rate in the Sephardic Jewish population:
Carrier screening is most commonly done by complete blood count (CBC) and hemoglobin electrophoresis, which detects almost all carriers. At least 6 common mutations have been identified in the Moroccan Jewish population and at least 4 in the Iranian Kurdish Jewish population. Detection rates for mutation analysis varies by screening panel.

For More information:

NIH: http://ghr.nlm.nih.gov/condition/beta-thalassemia