Mutations in the beta-globin gene cluster occur at high frequencies (>1%) in regions including the Mediterranean, Middle East, northern Africa, India, and almost all of Southeast Asia.[3]Flint J, Harding RM, Boyce AJ, et al. The population genetics of the haemoglobinopathies. Baillieres Clin Haematol. 1993 Mar;6(1):215-62.
https://www.doi.org/10.1016/s0950-3536(05)80071-x
http://www.ncbi.nlm.nih.gov/pubmed/8353314?tool=bestpractice.com
These mutations have arisen spontaneously, and it has been proposed that the carrier state for this disorder and others such as sickle cell disease may confer a survival advantage in areas where malaria is endemic.[4]Weatherall DJ. Common genetic disorders of the red cell and the "malaria hypothesis". Ann Trop Med Parasitol. 1987 Oct;81(5):539-48.
http://www.ncbi.nlm.nih.gov/pubmed/3331243?tool=bestpractice.com
Plasmodium falciparum parasitemia is reduced in vitro in beta-thalassemia.[5]Pathak V, Colah R, Ghosh K. Effect of inherited red cell defects on growth of Plasmodium falciparum: an in vitro study. Indian J Med Res. 2018 Jan;147(1):102-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967204
http://www.ncbi.nlm.nih.gov/pubmed/29749368?tool=bestpractice.com
The higher concentration of fetal hemoglobin (HbF) found in the red cells of people with hemoglobinopathies inhibits the development of the malarial parasite, but the mechanism of this effect is not well understood.[6]Pasvol G, Weatherall DJ, Wilson RJ. Effects of foetal haemoglobin on susceptibility of red cells to plasmodium falciparum. Nature. 1977 Nov 10;270(5633):171-3.
http://www.ncbi.nlm.nih.gov/pubmed/337159?tool=bestpractice.com
[7]Brockelman CR, Wongsattayanont B, Tan-ariya P, et al. Thalassemic erythrocytes inhibit in vitro growth of plasmodium falciparum. J Clin Microbiol. 1987 Jan;25(1):56-60.
https://jcm.asm.org/content/25/1/56.full.pdf
http://www.ncbi.nlm.nih.gov/pubmed/3539999?tool=bestpractice.com
Although the prevalence of these mutations is lower in the populations of northern Europe and North America, widespread immigration has led to worldwide distribution.[8]Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008 Jun;86(6):480-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647473
http://www.ncbi.nlm.nih.gov/pubmed/18568278?tool=bestpractice.com
Approximately 1.5% of the global population are heterozygous (carriers) for beta-thalassemias.[9]De Sanctis V, Kattamis C, Canatan D, et al. β-thalassemia distribution in the old world: an ancient disease seen from a historical standpoint. Mediterr J Hematol Infect Dis. 2017 Feb 20;9(1):e2017018.
https://www.mjhid.org/index.php/mjhid/article/view/2017.018
http://www.ncbi.nlm.nih.gov/pubmed/28293406?tool=bestpractice.com
Compound heterozygosity of beta-thalassemia with hemoglobin E mutations may have a phenotype similar to beta-thalassemia major or intermedia. The gene frequency for the hemoglobin E mutation is high in Thailand, Laos, Cambodia, and parts of southern China.[10]Nuntakarn L, Fucharoen S, Fucharoen G, et al. Molecular, hematological and clinical aspects of thalassemia major and thalassemia intermedia associated with Hb E-beta-thalassemia in Northeast Thailand. Blood Cells Mol Dis. 2009 Jan-Feb;42(1):32-5.
http://www.ncbi.nlm.nih.gov/pubmed/18951049?tool=bestpractice.com
It is estimated that over 90% of children born with significant beta-thalassemia syndromes are from Asia, India, and the Middle East, and a large number involve hemoglobin E mutations.[11]Colah R, Gorakshakar A, Nadkarni A. Global burden, distribution and prevention of beta-thalassemias and hemoglobin E disorders. Expert Rev Hematol. 2010 Feb;3(1):103-17.
http://www.ncbi.nlm.nih.gov/pubmed/21082937?tool=bestpractice.com
In the developed world, newborn screening ensures early diagnosis and referral to the appropriate hematology service for management.