let's recode the building blocks
Beta-thalassemia (β-thalassemia) or beta-thal is a severe genetic disease that is characterized by significantly reduced or absent production of functional adult beta (β)-globin, a component of an oxygen-carrying protein called hemoglobin.i,ii
Beta-thal is caused by mutations in the β-globin (HBB) gene. Individuals with beta-thal minor have a mutation in one HBB gene, while individuals with the intermediate and major forms have mutations in both HBB genes.iii The absence of sufficient β-globin impairs development and survival of healthy red blood cells (RBCs), which can eventually lead to anemia, fatigue and other issues, as it impacts the delivery of oxygen in an individual’s blood cells.iii Mild forms of beta-thal may not need treatment.iii
Transfusion-dependent β-thalassemia (TDT) is the most severe form of the disease, characterized by severe anemia, and requiresiii lifelong, regular blood transfusions to maintain Hb levels. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.iv,v Effective management of iron overload requires lifelong iron chelation therapy.iv,vi,vii
What are the symptoms?
RBCs carry oxygen to all cells and tissues of the body. Since oxygen is a fuel that all cells require to function, when there are not enough healthy RBCs, there is also not enough oxygen delivered to all the other cells of the body. This condition is called anemia, and people may feel tired, weak or short of breath.viii If left untreated, severe anemia can damage organs and potentially lead to death.ix
How common is beta-thal?
Beta-thal is estimated to affect approximately 1 in 100,000 individuals in the general population.iii
The incidence and prevalence of beta-thal is geographically variable, with endemic populations primarily found in South Asia, the Middle East, North Africa, and Southern Europe. While migration is changing the global distribution of the disease, beta-thal is a rare disease in most of Europe and the U.S.i,iv,x The CDC states that beta-thal major (a subset of beta-thal) affects at least 1,000 people in the U.S., however, the exact prevalence of beta-thal in the U.S. is not known and it is expected to increase with rising rates of immigration from endemic countries.xi,xii
- Prevalence of beta-thal is variable in Europe, with <1000 patients in most nonendemic countriesxiii,xiv,xv,xvi
- In Italy, where beta-thal is endemic, there are approximately 6500 patients with TDTxvii
- In both Europe and the U.S., the prevalence of beta-thal has risen as a result of immigration from endemic countriesi,xiii,xiv,xv
How is it diagnosed?
Initially, beta-thal is diagnosed through an examination of the blood, including a complete blood count and specific hemoglobin analysis. Genotype evaluation may also be needed.iii
People with moderate and severe forms of thalassemia usually find out about their condition in childhood, as they have symptoms of severe anemia early in life. Because thalassemias are inherited, the condition usually runs in families. Some people find out about their thalassemia because they have relatives with a similar condition.ix
What is the effect of beta-thal?
Patients with beta-thal do not make enough healthy red blood cells and typically need RBC transfusions every two to five weeks to reduce the symptoms of anemia.iv,vii,viii,xix Because people with TDT cannot survive without regular blood transfusions, they require a lifetime of hospital visits as well as chelation therapy, which is needed to reduce excess iron caused by chronic blood transfusions – all of which compounds the challenges of managing this disease.iv
Despite the availability of supportive care, many people with beta-thal experience serious complications and organ damage due to iron overload.iv By eliminating or reducing the need for blood transfusions, the long-term complications associated with beta-thal may be reduced.iv Addressing the underlying genetic cause of beta-thal through gene therapy has the potential to restore the capacity of the patient’s own blood-forming stem cells to generate RBCs with a normal hemoglobin content, with the goal of achieving transfusion-independence.iv
Find out more.
You can find more information about beta-thal by visiting patient resources.
iGalanello R, Origa R. Beta-thalassemia. Orphanet J RareDis. 2010;5:11. iiThein SL. The molecular basis of β-thalassemia. Cold Spring Harb Perspect Med. 2013;3(5):a011700. iiiNational Organization for Rare Disorders (NORD). Beta thalassemia. Available at https://rarediseases.org/rare-diseases/thalassemia-major/. Accessed March 2021. ivCappellini MD, Cohen A, Porter J, Taher A, Viprakasit V, eds. Guidelines for the management of transfusion-dependent thalassaemia [TDT]. 3rd ed. Nicosia, Cyprus: Thalassaemia International Federation; 2014. vBonifazi F, Conte R, Baiardi P, et al. Pattern of complications and burden of disease in patients affected by beta-thalassemia major. Curr Med Res Opin. 2017;33(8):1525-1533. viK. Bayanzay. Reducing the iron burden and improving survival in transfusion-dependent thalassemia patients: current perspectives. Journal of Blood Medicine. 6 August 2016: 7 159-169. viiMusallam KM, Angastiniotis M, Eleftheriou A, Porter JB. Cross-talk between available guidelines for the management of patients with beta-thalassemia major. Acta Haematol. 2013;130(2):64-73. viiiNIH National Heart, Lung, and Blood Institute. Anemia. Available at https://www.nhlbi.nih.gov/health-topics/anemia. Accessed March 2021. ixCenters for Disease Control and Prevention. What is Thalassemia? Page last reviewed: April 2020. Available at https://www.cdc.gov/ncbddd/thalassemia/facts.html. Accessed March 2021. xColah R, Gorakshakar A, Nadkarni A. Global burden, distribution and prevention of β-thalassemias and hemoglobin E disorders. Expert Rev Hematol. 2010;3(1):103-117. xiSayani FA, Kwiatkowski JL. Increasing prevalence of thalassemia in America: implications for primary care. Ann Med. 2015;47(7):592-604. xiiCenters for Disease Control and Prevention. Thalassemia Awareness. 2020. Page last reviewed: May 2020. Available at https://www.cdc.gov/ncbddd/thalassemia/features/international-thalassemia.html. Accessed March 2021. xiiiCario H, Stahnke K, Sander S, Kohne E. Epidemiological situation and treatment of patients with thalassemia major in Germany: results of the German multicenter β-thalassemia study. Ann Hematol. 2000;79(1):7-12. xivHemminki K, Li X, Forsti A, Sundquist J, Sundquist K. Thalassemia and sickle cell anemia in Swedish immigrants: genetic diseases have become global. SAGE Open Med. 2015;3:2050312115613097. xvThuret I, Pondarre C, Loundou A, et al. Complications and treatment of patients with β-thalassemia in France: results of the National Registry. Haematologica. 2010;95(5):724-729. xviUK National Hemoglobinopathies Registry. Number of Patients by Diagnosis as of March 22, 2018. NHR Information Service Reports. 2018. Available at http://nhr.mdsas.com/wp-content/uploads/2018/03/NumberPatientsDiagnosis.pdf. Accessed March 2021. xviiAngelucci E, Antmen AB, Losi S, Burrows N, Bartiromo C, Hu XH. Direct medical care costs associated with β-Thalassemia care in Italy. Blood. 2017;130(Suppl 1):92-5599. [abstract] xviiiYardumian A, Telfer P, Shah F, et al. United Kingdom Thalassemia Society standards for the clinical care of children and adults with thalassaemiain the UK. 3rd ed. United Kingdom Thalassemia Society; 2016. Available at https://ukts.org/wp-content/uploads/2019/12/Standards-2016final.pdf. Accessed March 2021. xixVichinsky E, Levine L, eds. Standards of care guidelines for thalassemia. Oakland, CA: Children’s Hospital & Research Center Oakland; 2012.