Thalassaemias

David J Weatherall, University of Oxford, Oxford, UK

Published online: April 2010

DOI: 10.1002/9780470015902.a0002274.pub2

The thalassaemias are the commonest genetic disorders in humans and present an increasing public health problem in the tropical countries in which they occur at a high frequency. There are many different forms of thalassaemia, all resulting from mutations of the genes which are responsible for regulating the structure and synthesis of haemoglobin. These diseases are all transmitted in a Mendelian fashion; parents, who are symptomless carriers, each pass on a defective gene to a severely affected offspring. The extremely high frequency of these diseases reflects natural selection whereby symptomless carriers are more resistant to different forms of malaria. A better understanding of the genetic basis of these diseases has led to improvements in their prevention and symptomatic treatment.

Key Concepts:

  • The haemoglobinopathies, thalassaemia and sickle cell disease, are by far the commonest genetic disorders.
  • These diseases have reached their high frequency mainly due to natural selection through heterozygote protection against malaria.
  • Thalassaemias consist of several different disorders, each due to many different underlying mutations of the globin genes.
  • All the severe forms of thalassaemia show a remarkable clinical variability which reflects both genetic modifiers, adaption to anaemia and the environment.
  • All the different forms of thalassaemia can be identified in fetal life and hence prenatal diagnosis is possible.
  • A cure of thalassaemia is only possible by bone marrow transplantation when suitable donors are available.
  • Most serious forms of thalassaemia are amenable to symptomatic treatment with transfusion and drugs to remove excess iron.

Keywords: thalassaemia; haemoglobin; anaemia

Figure 1. World distribution of the thalassaemias. Each population has a different set of mutations. These are described either by the nucleotide base position in introns (IVS 1 or 2) or in the particular codons in exons. Mutations that are given the prefix are those in the 5¢ noncoding regions of the globin genes. Those marked polyA are mutations in the 3¢ noncoding regions. bp, base pair.
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 Further Reading
    book Steinberg MH, Forget BG, Higgs DR and Weatherall DJ (eds) (2009) Disorders of Hemoglobin. New York: Cambridge University Press.
    book Weatherall DJ, Akinyanju O, Fucharoen S, Olivieri NF and Musgrove P (2006) "Inherited disorders of hemoglobin". In: Jamison DT, Breman JG, Measham AR, Alleyne G, Claeson M, Evans DB, Jha P, Mills A and Musgrove P (eds) Disease Control Priorities in Developing Countries, 2nd edn, pp. 663–680. New York: Oxford University Press and the World Bank.
    book Weatherall DJ, Clegg JB, Higgs DR and Wood WG (2001) "The hemoglobinopathies". In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B and Vogelstein B (eds) The Metabolic and Molecular Bases of Inherited Disease, 8th edn, pp. 4571–4638. New York: McGraw-Hill.

Related Sub-Topics:

Specific Genetic Disorders | Mutational Mechanisms of Genetic Disease | Inter-Individual Variation and Polymorphism | Biomolecular Interactions | Proteins: Structure, Function, Metabolism
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Article Title: Thalassaemias
 
How to Cite close
Weatherall, David J(Apr 2010) Thalassaemias. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002274.pub2]