title: β-Thalassemia Distribution in the Old World: an Ancient Disease Seen from a Historical Standpoint.
abstract: 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 (βo) 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 from the Mediterranean basin, throughout the Middle East, the Indian subcontinent, Southeast Asia, and Melanesia to the Pacific Islands.
  
  
  OBJECTIVE
  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 β-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 specific mutations in individual populations, 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 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.
authors.affiliation: Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Sanctis
authors.affiliation: First Department of Paediatrics, University of Athens, Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Kattamis
authors.affiliation: Director of Thalassemia Diagnosis Center of Mediterranean Blood Diseases Foundation, Antalya, Turkey.
authors.forename: Duran
authors.initials: D
authors.lastname: Canatan
authors.affiliation: Department of Pediatrics, Division of Endocrinology, Alexandria University Children's Hospital, Alexandria, Egypt.
authors.forename: Ashraf T
authors.initials: AT
authors.lastname: Soliman
authors.affiliation: Department of Pediatrics, Ain Shams University, Cairo, Egypt.
authors.forename: Heba
authors.initials: H
authors.lastname: Elsedfy
authors.affiliation: Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mehran
authors.initials: M
authors.lastname: Karimi
authors.affiliation: Department of Haematology, College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman.
authors.forename: Shahina
authors.initials: S
authors.lastname: Daar
authors.affiliation: Pediatric Hematology Unit, Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman and Department of Pediatrics, Alexandria University Children's Hospital, Egypt.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Wali
authors.affiliation: National Center for Cancer Care and Research, Medical Oncology Hematology Section HMC, Doha, Qatar.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Yassin
authors.affiliation: Primary Health Care, Ministry of Health, Alexandria, Egypt.
authors.forename: Nada
authors.initials: N
authors.lastname: Soliman
authors.affiliation: Professor, Pediatric Hemato-Oncology, Christian Medical College and Hospital, Ludhiana, Punjab, India.
authors.forename: Praveen
authors.initials: P
authors.lastname: Sobti
authors.affiliation: Head, Division of Pediatric Hematology Oncology, Deputy Chair of Hematology and Head, Section of Hematology Research Lab, King Fahd Medical Research Center, Department of Hematology Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Soad
authors.initials: S
authors.lastname: Al Jaouni
authors.affiliation: Department of Pediatrics, Ain Shams University, Cairo, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Kholy
authors.affiliation: Department of Pediatrics, NYU School of Medicine, New York, USA.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Fiscina
authors.affiliation: Medical Advisor, Thalassemia International Federation (TIF), Nicosia, Cyprus.
authors.forename: Michael
authors.initials: M
authors.lastname: Angastiniotis
keywords: Ancient disease; Old World; Thalassemia distribution