Vincenzo De Sanctis
  • Vincenzo De Sanctis
    Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara, Italy., Italy | vdesanctis@libero.it



Background: Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. β -thalassaemia is characterised by the reduced synthesis (β +) or absence (β o) of the β-globin chains in the HbA molecule, resulting in accumulation of  excess unbound α-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 β-thalassemias: there is a high incidence in populations extending from the Mediterranean basin throughout the Middle East, the Indian subcontinent, Southeast Asia, Melanesia and into the Pacific Islands

Aim: The principal aim of this paper is to review, from a historical standpoint, our knowledge about an ancient disease, the β-thalassemias, and  in particular, when, how and in what way β-thalassemia spread worldwide to reach such high incidences in certain populations.



Results: Mutations involving the ß-globin gene are the most common cause of genetic disorders  in humans. To date, more than 350 β -thalassaemia mutations have been reported. Considering the current distribution of β- thalassemia, the wide diversity of mutations and the small number of individual population’s specific mutations, it seems unlikely that β-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 β-thalassemia mutations could well be explained by looking at its geographical distribution, the history of malaria, wars, invasions, mass migrations, consanguinity and settlements. The analysis of the molecular spectrum and distribution of haemoglobinopathies allows for the development and improvement of diagnostic tests and management for these disorders.


Thalassemia distribution

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Weatherall DJ, Clegg JB. 2001. The thalassaemia syndromes. 4th Edition. Oxford: Blackwell Science Ltd 2001.

Thein SL. The molecular basis of β-thalassemia. Cold Spring Harb Perspect Med. 2013 May 1;3(5):a011700. doi: 10.1101/cshperspect.a011700

Cao A, Galanello R. Beta-thalassemia. Genet Med.2010; 12, 61–76

Kountouris P, Lederer CW, Fanis P, Feleki X, Old J, Kleanthous M. IthaGenes: an interactive database for haemoglobin variations and epidemiology. PLoS One. 2014 Jul 24;9(7):e103020. doi: 10.1371/journal.pone.0103020. eCollection 2014.

Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med. 2005;353:1135-1146

Williams TN, Weatherall DJ. World distribution, population genetics, and health burden of the hemoglobinopathies. Cold Spring Harb Perspect Med. 2012 Sep 1;2(9):a011692

Basak AN.The molecular pathology of beta-thalassemia in Turkey: the Boğaziçi University experience. Hemoglobin. 2007;31:233-241

Chehab FF, Der Kaloustian V, Khouri FP, Deeb SS, Kan YW. The molecular basis of beta-thalassemia in Lebanon: application to prenatal diagnosis. Blood 1987;69:1141–1145

El-Hazmi MA, al-Swailem AR, Warsy AS. Molecular defects in beta-thalassaemias in the population of Saudi Arabia. Hum Hered.1995;45:278–285

Zhong Chen L, Easteal S, Board PG. Evolution of the β-globin haplotypes in human populations. Mol Biol Evol. 1990;7: 423–437

Del Senno L, Pirastu M, Barbieri R, Bernardi F, Buzzoni D, Marchetti G, Perrotta C, Vullo C, Kan YW, Conconi F. beta (+)-Thalassaemia in the Po River Delta region (northern Italy): genotype and beta globin synthesis. J Med Genet. 1985;22:54-58

Pirastu M, Saglio G, Camaschella C, Loi A, Serra A, Bertero T, Gabutti W, Cao A. Delineation of specific beta-thalassemia mutations in high-risk areas of Italy: a prerequisite for prenatal diagnosis. Blood 1987;71:983–988

Amselem S, Nunes V, Vidaud M, Estivill X, Wong C, d'Auriol L, Vidaud D, Galibert F, Baiget M, Goossens M. Determination of the spectrum of beta-thalassemia genes in Spain by use of dot-blot analysis of amplified beta-globin DNA. Am J Hum Genet. 1988; 43:95–100

Faustino P, Pacheco P, Loureiro P, Nogueira PJ, Lavinha J. The geographic pattern of beta-thalassaemia mutations in the Portuguese population. Br J Haematol. 1999;107:903–904

Fattoum S, Guemira F, Oner C, Li HW, Kutlar F, Huisman TH. Beta-thalassemia, HB S-beta-thalassemia and sickle cell anemia among Tunisians. Hemoglobin. 1991;15:11–21

Falchi A, Giovannoni L, Vacca L, Latini V, Vona G, Varesi L. beta-globin gene cluster haplotypes associated with beta-thalassemia on Corsica island. Am J Hematol. 2005;78:27-32

Maggio A, Giambona A, Cai SP, Wall J, Kan YW, Chehab FF. Rapid and simultaneous typing of hemoglobin S, hemoglobin C, and seven Mediterranean beta-thalassemia mutations by covalent reverse dot-blot analysis: application to prenatal diagnosis in Sicily. Blood.1993;81:239–242

Kountouris P, Kousiappa I, Papasavva T, Christopoulos G, Pavlou E, Petrou M, Feleki X, Karitzie E, Phylactides M, Fanis P, Lederer CW, Kyrri AR, Kalogerou E, Makariou C, Ioannou C, Kythreotis L, Hadjilambi G, Andreou N, Pangalou E, Savvidou I, Angastiniotis M, Hadjigavriel M, Sitarou M, Kolnagou A, Kleanthous M, Christou S. The molecular spectrum and distribution of haemoglobinopathies in in Cyprus: a 20-year retrospective study. Sci Rep. 2016 May 20;6:26371. doi: 10.1038/srep26371.

Baysal E, Indrak K, Bozkurt G, Berkalp A, Aritkan E, Old J, Ioannou P, Angastiniotis M, Droushiotou A, Yüregir GT. The beta thalassaemia mutations in the population of Cyprus. Br J Haematol. 1992; 81: 607-609

Kyrri AR, Felekis X, Kalogerou E, Wild BJ, Kythreotis L, Phylactides M, Kleanthous M. Hemoglobin variants in Cyprus. Hemoglobin. 2009;33:81-94

Malamos B, Fessas Ph, Stamatoyiannopoulos G. Types of thalassemia trait carriers, as revealed by a study of their incidence in Greece. Br J Haemat. 1962;8:5-14

Loukopoulos D. Current Status of thalassemia and sickle cell syndromes in Greece .Sem Hematol.1996;33:76-86

Kattamis C, Hu H, Cheng G, Reese J, Gonzalez-Redondo M Kutlar A, Kutlar F, Huisman THJ. Molecular characterization of β–thalassemia in 174 Greek patients with thalassemia major. Br.J Haem.1990;74:342-346

Canatan D. Thalassemias and hemoglobinopathies in Turkey. Hemoglobin. 2014;38:305-307

Tadmouri GO, Garguier N, Demont J, Perrin P, Başak AN Tadmouri. History and origin of beta-thalassemia in Turkey: sequence haplotype diversity of beta-globin genes. Hum Biol. 2001;73:661-74

Aksoy M, Ikin EW, Mourant AE Lehmann H. Blood groups, haemoglobins, and thalassaemia in Turks in southern Turkey and Eti-Turks. Br Med J. 1958;2:937-939

Hamamy HA, Al-Allawi NA. Epidemiological profile of common haemoglobinopathies in Arab countries. J Community Genet. 2013;4:147-167

Agouti I, Badens C, Abouyoub A, Levy N, Bennani M. Molecular basis of beta-thalassemia in Morocco: possible origins of the molecular heterogeneity. Genet Test. 2008;12:563-568

Daar S, Gravell D, Hussein HM, Pathare AV, Wali Y, Krishnamoorthy R. Haematological and clinical features of beta-thalassaemia associated with Hb Dhofar.Eur J Haematol. 2008;80:67-70

De Leo R, Deidda G, Novelletto A, El-Kalla S, Mathews AR, Felicetti L. Analysis of β-thalassemia mutations in the United Arab Emirates provides evidence for recurrent origin of the IVSI nt 5 (G-C) mutation. Hum Mutat. 1995;5:327–328

Kyriacou K, Al-Quobaili F, Pavlou E, Christopoulos G, Ioannou P, Kleanthous M. Molecular characterization of β-thalassemia in Syria. Hemoglobin. 2000;24:1–13

Zahed L, Qatanani M, Nabulsi M, Taher A. β- thalassemia mutations and haplotype analysis in

Lebanon. Hemoglobin. 2000;24:269–276

Filon D, Oron V, Shawa R, Shawa R, Elborno E, Najjar K, Tulchinsky T, Rachmilewitz E, Rund D, Oppenheim A. Spectrum of β- thalassemia mutations in the Gaza area. Hum Mutat. 1995;5:351–353

Jassim N, Merghoub T, Pascaud O, al Mukharraq H, Ducrocq R, Labie D, Elion J, Krishnamoorthy R, Arrayed SA. Molecular basis of β-thalassemia in Bahrain. Ann NY Acad Sci. 1998;850:407–409

El-Hashemite N, Petrou M, Khalifa AS, Heshmat NM, Rady MS, Delhanty JD. Identification of novel Asian Indian and Japanese mutations causing β-thalassemia in Egyptian population. Hum Genet 1997;99:271-274.

El-Shanshory M, Hagag A, Shebl S, Badria I, Abd Elhameed A, Abd El-Bar E, Al-Tonbary Y, Mansour A, Hassab H, Hamdy M, Alfy M, Sherief L, Sharaf E. Spectrum of beta globin gene mutations in Egyptian children with β-Thalassemia. Mediterr J Hematol Infect Dis. 2014 Nov 1;6(1):e2014071

Al-Allawi NA, Al-Mousawi BM, Badi AI, Jalal SD.The spectrum of β-thalassemia mutations in Baghdad, Central Iraq. Hemoglobin. 2013;37:444-453

Al-Obaidli A, Hamodat M, Fawzi Z, Abu-Laban M, Gerard N, Krishnamoorthy R. Molecular basis of thalassemia in Qatar. Hemoglobin. 2007;31:121-127

Al-Obaidli A, Gerard N, Al Zadjali S, Fawzi Z, Pravin S, Pathare A, Krishnamoorthy R. A novel deletional betathalassemic variant in an ethnic Qatari patient. Hemoglobin. 2009; 33:214-219.

Haj Khelil A, Denden S, Leban N, Daimi H, Lakhdhar R, Lefranc G, Ben Chibani J, Perrin P. Hemoglobinopathies in North Africa: a review. Hemoglobin. 2010;34:1-23

Zahed L. The spectrum of beta-thalassemia mutations in the Arab populations. J Biomed Biotechnol. 2001;1:129-132

Tadmouri GO, Gulen RI. Deniz: the electronic database for beta-thalassemia mutations in the Arab world. Saudi Med J. 2003;24:1192-1198

Sadiq MFG, Huisman THJ. Molecular characterization of β-thalassemia in North Jordan. Hemoglobin.1994;18:325–332

Adekile AD, Gu LH, Baysal E, Haider MZ, al-Fuzae L, Aboobacker KC, al-Rashied A, Huisman TH. Molecular characterization of alpha thalassemia determinants, beta thalassemia alleles and beta S haplotypes among Kuwaiti Arabs. Acta Haematol. 1994;92:176–181

Fattoum S, Guemira F, Oner C, Li HW, Kutlar F, Huisman TH.. Beta-thalassemia, HbS-beta-thalassemia and sickle cell anemia among Tunisians. Hemoglobin. 1991;15:11–21

Maryami F, Azarkeivan A, Fallah MS, Zeinali S. A large cohort study of genotype and phenotype correlations of beta-thalassemia in Iranian population. Int J Hematol Oncol Stem Cell Res. 2015;9:198-202

Varawalla NY, Fitches AC, Old JM. Analysis of beta-globin gene haplotypes in Asian Indians: origin and spread of beta-thalassaemia on the Indian subcontinent. Hum Genet. 1992;90:443-449

Rezaee AR, Banoei MM, Khalili E, Houshmand M. Beta-Thalassemia in Iran: new insight into the role of genetic admixture and migration. Sc World J. 2012; 2012:635183. doi: 10.1100/2012/635183. Epub 2012 Dec 18

Harcourt AH. Human phylogeography and diversity. Proc Natl Acad Sci USA. 2016;113:8072- 8078

Lahr MM, Foley RA. Towards a theory of modern human origins: geography, demography, and diversity in recent human evolution. Am J Phys Anthropol. 1998;Suppl 27:137-176

Liu H, Prugnolle F, Manica A, Balloux F. A geographically explicit genetic model of worldwide human-settlement history. Am J Hum Genet. 2006;79:230-237

Mellars P. Why did modern human populations disperse from Africa ca. 60,000 years ago? A new model. Proc. Natl. Acad. Sci. USA.2006; 103:9381– 9386

O’Connell J. Allen J. Dating the colonization of the Sahul (Pleistocene Australia-New Guinea): A review of recent research. J Archaeol Sc. USA.2004; 31:835– 853

Armitage SJ, Jasim SA, Marks AE, Parker AG, Usik VI, Uerpmann HP. The southern route "out of Africa": evidence for an early expansion of modern humans into Arabia. Science. 2011;331:453-456

Forster P, Matsumura S. Evolution. Did early humans go north or south? Science. 2005; 308: 965-966.

Stringer C. Palaeoanthropology. Coasting out of Africa. Nature. 2000;405:24-25

Childe VG. New light on the most ancient east. London: Routledge and Paul, 4th ed.1952

Bar-Yosef O. On the nature of transitions: the middle to upper Palaeolithic and the Neolithic revolution. Cambridge Archaeol J. 1998;8:141–163

Bar-Yosef O, Kislev M. Early farming communities in the Jordan Valley. In: Harris DR, Hillman GC, eds. Foraging and farming. The evolution of plant exploitation. London: Unwin Hyman, 1989; pp. 633–642

Zohary D, Hopf M, Weiss R. Domestication of plants in the old world, 4th ed. New York: Oxford University Press. 2012; pp.1-264

Araus JL, Ferrio JP, Buxó R, Voltas J. The historical perspective of dryland agriculture: lessons learned from 10,000 years of wheat cultivation. J Exp Bot. 2007;58:131-145

Araus JL, Ferrio JP, Buxó R, Voltas J. The historical perspective of dryland agriculture: lessons learned from 10,000 years of wheat cultivation. J Exp Bot. 2007;58:131-145

Angel JL. Porotic hyperostosis, anemias, malarias, and marshes in the prehistoric eastern Mediterranean. Science. 1966;153:760-763

Salamini F, Ozkan H, Brandolini A, Schäfer-Pregl R, Martin W. Genetics and geography of wild cereal domestication in the near east. Nat Rev Genet. 2002;3:429-441

Kenoyer JM, Price TD, Burton JH.A new approach to tracking connections between the Indus Valley and Mesopotamia: initial results of strontium isotope analyses from Harappa and Ur. J Archaeol Sci.2013;40: 2286–2297.

Crawford HEW.Sumer and the Sumerians: Cambridge University Press.

Wiercinski A. Anthropology of ancient Mesopotamia.On: Mesopotamia, Ed. Braun, PWN - National Scientific Publishing. 1997; pp 42–45

Araus JL, Buxo´ R. Changes in carbon isotope discrimination in grain cereals from the north-western Mediterranean Basin during the past seven millenia. Aust J Plant Physiol.1993; 20:117–128

Buxo´ R. Arqueologı´a de las plantas: la explotacion economica de las semillas y los frutos en el marco mediterraneo de la Penınsula Iberica. Barcelona: Crıtica, Grijalbo eds, 1998; pp- 1-367

Feldman M. Origin of cultivated wheat. In: Bonjean AP, Angus WJ, eds. The world wheat book. a history of wheat breeding. Paris: Lavoisier Publishing, 2001; pp .3–57.

Iandola F. La thalassemia dall’alba della civiltà occidentale ad oggi. Tesi di Laurea, In: Fondazione De Marchi, www.demarchi.org/thalassemia.htm

Grmek MD. Malaria in the Eastern Mediterranean in prehistory and antiquity. Parassitologia, 1994;36:1–6.

Silvestroni E, Bianco I, Alfieri N. Sulle origini della microcitemia in Italia e nelle altre regioni della terra. Medicina.1952; 2: 187–216

Choremis C, Fessas Ph, Kattamis C, Stamatoyiannopoulos G, Zannos-Mariolea L, Karaklis A, Belios G. Three inherited red-cell abnormalities in a district of Greece. Thalassemia, sickling and glucose-6-phosphate-dehydrogenase deficiency. Lancet 1963;1; 907-909

Flint J, Harding RM, Boyce AJ, Clegg JB. The population genetics of the haemoglobinopathies. Baillieres Clin Haematol. 1998;11:1-51

Haldane JBS: Disease and evolution. La Ricerca Scientifica 1949, 19:68–76.

Canali S. Researches on thalassemia and malaria in Italy and the origins of the "Haldane hypothesis". Med Secoli. 2008;20:827-846

Ratcliffe AW. The historical background of malaria; a reconsideration. J Indiana State Med Assoc. 1946;39:339-347

Bruce-Chwatt LJ. Aleogenesis and paleo-epidemiology of primate malaria. Bull World Health Organ.1965;32:363-387

Fairhurst RM, Baruch DI, Brittain NJ, Ostera GR, Wallach JS, Hoang HL, Hayton K, Guindo A, Makobongo MO, Schwartz OM, Tounkara A, Doumbo OK, Diallo DA, Fujioka H, Ho M, Wellems TE. Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria. Nature. 2005;435:1117–1121.

Cholera R, Brittain NJ, Gillrie MR, Lopera-Mesa TM, Diakité SA, Arie T, Krause MA, Guindo A, Tubman A, Fujioka H, Diallo DA, Doumbo OK, Ho M, Wellems TE, Fairhurst RM. Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin. Proc Natl Acad Sci U S A. 2008;105:991–996

Cyrklaff M, Sanchez CP, Kilian N, Bisseye C, Simpore J, Frischknecht F, Lanzer M.. Hemoglobins S and C Interfere with Actin Remodeling in Plasmodium falciparumâ]“Infected Erythrocytes. Science. 2011 Dec 2;334(6060):1283-6.

Williams TN, Mwangi TW, Roberts DJ, Alexander ND, Weatherall DJ, Wambua S, Kortok M, Snow RW, Marsh K. An immune basis for malaria protection by the sickle cell trait. PLoS Med. 2005 May;2(5):e128

Gong L, Maiteki-Sebuguzi C, Rosenthal PJ, Hubbard AE, Drakeley CJ, Dorsey G, Greenhouse B.Evidence for both innate and acquired mechanisms of protection from Plasmodium falciparum in children with sickle cell trait. Blood. 2012 Apr 19;119(16):3808-14. doi: 10.1182/blood-2011-08-371062

Veenemans J, Jansen EJ, Baidjoe AY, Mbugi EV, Demir AY, Kraaijenhagen RJ, Savelkoul HF, Verhoef H.Effect of alpha (+) -thalassaemia on episodes of fever due to malaria and other causes: a community-based cohort study in Tanzania. Malar J. 2011 Sep 22;10:280. doi: 10.1186/1475-2875-10-280

Tan X, Traore B, Kayentao K, Ongoiba A, Doumbo S, Waisberg M, Doumbo OK, Felgner PL, Fairhurst RM, Crompton PD. Hemoglobin S and C heterozygosity enhances neither the magnitude nor breadth of antibody responses to a diverse rray of Plasmodium falciparum antigens. J Infect Dis. 2011 Dec;204(11):1750–1761

Cabrera G, Cot M, Migot-Nabias F, Kremsner PG, Deloron P, Luty AJ. The sickle cell trait is associated with enhanced immunoglobulin G antibody responses to Plasmodium falciparum variant surface antigens. J Infect Dis. 2005;191:1631–1638.

Ayi K, Turrini F, Piga A, Arese P. Enhanced phagocytosis of ring-parasitized mutant erythrocytes: a common mechanism that may explain protection against falciparum malaria in sickle trait and beta-thalassemia trait. Blood. 2004;104:3364–3371.

Christianson A, Howson CP, Modell B. March of Dimes global report on birth defects. March of Dimes Birth Defects Foundation, New York, 2009; pp.21-23

Rudra S, Chakrabarty P, Hossain MA, Ripon MJ, Rudra M, Mirza TT. Awareness among parents of β-Thalassemia major patients regarding prenatal diagnosis and premarital screening in day care centre of Transfusion Medicine Department. Mymensingh Med J. 2016;25:12-17

Canatan D, Karadoğan C, Oğuz N, Balta N, Coşan R: The frequency of consanguineous marriages in patients with hereditary blood disorders in South of Turkey. Community Genet. 2003.6:58

Moghadam M. Karimi M, Dehghani SJ, Dehbozorgian J, Montazeri S, Javanmardi E, Asadzade R, Amiri A, Saghatoleslam Z, Sotodegan F, Morshedi N, Imanifard J, Afrasiabi A. Effectiveness of β-thalassemia prenatal diagnosis in Southern Iran: a cohort study. Prenat Diagn. 2015; 35:1238-1242

Weatherall DJ. Thalassemia as a global health problem: Recent progress towards its control in the developing countries. Ann NY Acad Sci.2010; 1202: 17–23.

Webb S. Cranial thickening in an Australian hominid as a possible palaeoepidemiological indicator. Am J Phys Anthropol.1990;82:403-411

Hershkovitz I, Ring B, Speirs M, Galili E, Kislev M, Edelson G, Hershkovitz A. Possible congenital hemolytic anemia in prehistoric coastal inhabitants of Israel. Am J Phys Anthropol. 1991;85:7-13

Tayles N. Anemia, genetic diseases, and malaria in prehistoric mainland Southeast Asia. Am J Phys Anthropol. 1996;101:11-27

Aufderheide AC. Progress in paleopathology. Biomedical studies of human mummies. Minn Med.1998;81:28-31

Stuart-Macadam P. Porotic hyperostosis: new evidence to support the anemia theory. Am J Phys Anthropol. 1987;74:521-526.

Schultz M. Paleohistopathology of bone: a new approach to the study of ancient diseases. Am J Phys Anthropol. 2001;Suppl 33:106-147

Rabino Massa E.Conservazione dei Globuli in Tessuti di Mummie Egiziane. Archivio per L'Antropologia e L'Etnologia.La Nuova Italia.1967;3:181-182

Rabino Massa E. Presence of Thalassemia in Egyptian Mummies. J. Hum. Evol.1977; 6:223-225

Filon D, Faerman M, Smith P, Oppenheim A. Sequence analysis reveals a beta-thalassaemia mutation in the DNA of skeletal remains from the archaeological site of Akhziv, Israel. Nat Genet. 1995;9:365-368

Handt O, Krings M, Ward RH, Pääbo S. The retrieval of ancient human DNA sequences. Am J Hum Genet. 1996;59:368-376

Paabo S. 1989. Ancient DNA: extraction, characterization, molecular cloning, and enzy-matic amplification. Proc Natl Acad Sci USA.1989;86:1939-1943

Christianson A, Howson CP, Modell B. March of Dimes global report on birth defects. March of Dimes Birth Defects Foundation, New York, 2006

Aguilar Martinez P, Angastiniotis M, Eleftheriou A, Gulbis B, Mañú Pereira Mdel M, Petrova-Benedict R, Corrons JL. Haemoglobinopathies in Europe: health & migration policy perspectives. Orphanet J Rare Dis. 2014 Jul 1;9:97. doi: 10.1186/1750-1172-9-97

Giordano PC, Harteveld CL, Bakker E. Genetic epidemiology and preventive healthcare in multiethnic societies: the hemoglobinopathies. Int J Environ Res Public Health. 2014;11:6136-6146

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