Abstract
Background: Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. beta-thalassaemia is characterised by the reduced synthesis (beta(+)) or absence (beta degrees) of the beta-globin chains in the HbA molecule, resulting in accumulation of excess unbound alpha-globin chains that precipitate in erythroid precursors in the bone marrow and in the mature erythrocytes, leading to ineffective erythropoiesis and peripheral haemolysis. Approximately 1.5% of the global population are heterozygotes (carriers) of the beta-thalassemias; there is a high incidence in populations from the Mediterranean basin, throughout the Middle East, the Indian subcontinent, Southeast Asia, and Melanesia to the Pacific Islands.
Aim: The principal aim of this paper is to review, from a historical standpoint, our knowledge about an ancient disease, the beta-thalassemias, and in particular, when, how and in what way beta-thalassemia spread worldwide to reach such high incidences in certain populations.
Results: Mutations involving the beta-globin gene are the most common cause of genetic disorders in humans. To date, more than 350 beta-thalassaemia mutations have been reported. Considering the current distribution of beta-thalassemia, the wide diversity of mutations and the small number of specific mutations in individual populations, it seems unlikely that beta-thalassemia originated in a single place and time.
Conclusions: Various processes are known to determine the frequency of genetic disease in human populations. However, it is almost impossible to decide to what extent each process is responsible for the presence of a particular genetic disease. The wide spectrum of beta-thalassemia mutations could well be explained by looking at their geographical distribution, the history of malaria, wars, invasions, mass migrations, consanguinity, and settlements. An analysis of the distribution of the molecular spectrum of haemoglobinopathies allows for the development and improvement of diagnostic tests and management of these disorders.