The thalassaemias are the commonest genetic disorders in humans, representing an imbalance in the production of the α‐ and β‐globin chains which combine to form haemoglobin. The globin chain which is present in excess may precipitate in red cell precursors, causing oxidative damage and ineffective erythropoiesis. Patients with thalassaemia are therefore anaemic despite an expansion of erythroid activity in the bone marrow. In severe cases (thalassaemia major), regular blood transfusion is needed for survival. The high prevalence of thalassaemia in tropical regions is thought to reflect the relative resistance of carriers to falciparum malaria. Although bone marrow transplantation is currently the only curative treatment, intensive study of transcriptional regulation at the loci for the globin genes has highlighted the potential for gene therapy and gene editing. However, finding approaches to treatment that are practical for the majority of affected patients who live in low income regions of the world remains a major challenge.

Key Concepts

  • Thalassaemia results from an imbalance between α‐ and β‐globin chain production.
  • Its genetic basis is very variable, with α thalassaemia usually being caused by small deletions, and β thalassaemia normally due to point mutations.
  • The high gene frequency in areas of the world affected by malaria is thought to represent the protective effect of the carrier status.
  • Clinical consequences of thalassaemia include anaemia, bone marrow expansion and iron loading.
  • Iron loading may occur as a result of increased gastrointestinal absorption and, more significantly, due to regular blood transfusion.
  • The consequences of iron overload include hepatic, cardiac and endocrine dysfunction.
  • Bone marrow transplant remains the only curative treatment at present.
  • In the investigative context, individuals have attained transfusion independence through lentiviral gene therapy.
  • Efforts to reactive foetal haemoglobin therapeutically have focused on understanding BCL11a expression.

Keywords: thalassaemia; haemoglobin; anaemia; malaria; molecular pathology


Baronciani D, Angelucci E, Potschger U, et al. (2016) Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000–2010. Bone Marrow Transplantation 51 (4): 536–541.

Brendel C, Guda S, Renella R, et al. (2016) Lineage‐specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype. Journal of Clinical Investigation 126 (10): 3868–3878.

Camaschella C and Nai A (2016) Ineffective erythropoiesis and regulation of iron status in iron loading anaemias. British Journal of Haematology 172 (4): 512–523.

Fucharoen S and Weatherall DJ (2016) Progress toward the control and management of the thalassemias. Hematology/Oncology Clinics of North America 30 (2): 359–371.

Higgs DR, Engel JD and Stamatoyannopoulos G (2012) Thalassemia. Lancet 379 (9813): 373–383.

Hudecova I and Chiu RW (2017) Non‐invasive prenatal diagnosis of thalassemias using maternal plasma cell free DNA. Best Practice & Research. Clinical Obstetrics & Gynaecology 39: 63–73.

Jagannath VA, Fedorowicz Z, Al Hajeri A and Sharma A (2016) Hematopoietic stem cell transplantation for people with ß‐thalassemia major. Cochrane Database of Systematic Reviews 11: CD008708.

Jones E, Pasricha SR, Allen A, et al. (2015) Hepcidin is suppressed by erythropoiesis in hemoglobin E β‐thalassemia and β‐thalassemia trait. Blood 125 (5): 873–880.

Penman BS, Pybus OG, Weatherall DJ and Gupta S (2009) Epistatic interactions between genetics disorders of hemoglobin can explain why the sickle‐cell gene is uncommon in the Mediterranean. PNAS 106 (50): 21242–21246.

Sankaran VG and Orkin SH (2013) The switch from fetal to adult hemoglobin. Cold Spring Harbor Perspectives in Medicine 3 (1): a011643.

Sankaran VG, Xu J, Byron R, et al. (2011) A functional element necessary for fetal hemoglobin silencing. New England Journal of Medicine 365 (9): 807–814.

Smith EC and Orkin SH (2016) Hemoglobin genetics: recent contributions of GWAS and gene editing. Human Molecular Genetics 25 (R2): R99–R105.

Songdej D, Babbs C, Higgs DR and BHFS International Consortium (2017) An international registry of survivors with Hb Bart's hydrops fetalis syndrome. Blood 129 (10): 1251–1259.

Taylor SM, Parobek CM and Fairhurst RM (2012) Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta‐analysis. Lancet Infectious Diseases 12 (6): 457–468.

Vichinsky E (2016) Non‐transfusion‐dependent thalassemia and thalassemia intermedia: epidemiology, complications, and management. Current Medical Research and Opinion 32 (1): 191–204.

Wambua S, Mwangi TW, Kortok M, et al. (2006) The effect of alpha +‐thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya. PLoS Medicine 3 (5): e158.

Further Reading

Steinberg MH, Forget B, Higgs DR and Weatherall DJ (2009) Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management, 2nd edn. Cambridge, MA: Cambridge University Press.

Weatherall DJ and Clegg JB (1996) Thalassaemia: a global public health problem. Nature Medicine 2: 847–849.

Weatherall DJ (2001) Phenotype–genotype relationships in monogenic disease: lessons from the thalassaemias. Nature Reviews 2: 245–255.

Weatherall DJ and Clegg JB (2001a) The Thalassaemia Syndromes, 4th edn. Oxford, UK: Blackwell Scientific Publications.

Weatherall DJ and Clegg JB (2001b) Inherited hemoglobin disorders: an increasing global health problem. Bulletin of the World Health Organization 79: 704–711.

Weatherall DJ (2010) Thalassaemia. The Biography. Oxford, UK: Oxford University Press.

Weatherall DJ, Schechter AN and Nathan DJ (eds) (2013) Hemoglobin and its Disorders. New York, NY: Cold Spring Harbor Laboratory Press.

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Hay, Deborah, and Weatherall, David J() Thalassaemias. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005536.pub2]