Anemia in the Light of Genetic, Environmental and Cultural Factors: Cases of Some Ancient Anatolian Populations

Abstract

In this study, genetic, environmental and cultural factors of anemia are considered in the light of recent approaches in paleopathology. Porotic hyperostosis (PH) and cribra orbitalia (CO) are pathologic conditions which are seen in the form of porotic appearance on the cranial vault and orbital roofs. These conditions are described as consequences of marrow hyperplasia due to genetic or acquired chronic childhood anemia. Genetic anemias, such as thalassemia, sickle-cell anemia and anemia due to G6PD deficiency are balanced polymorphisms that are maintained by malaria. The geographic distributions of the aforementioned anemias are clearly linked to the spread of malaria in the history. Angel demonstrated that the common appearance of PH was a result of thalassemia in ancient Eastern Mediterranean (Angel 1964, 1966, 1967). Except for genetic anemias, the most supported explanation for the common appearance of PH and CO in skeletal populations has been the iron deficiency anemia. It has been suggested that iron deficiency anemia might be due to poor diet, gastrointestinal infections and parasitic infestations in children. The role of genetic anemias and acquired iron deficiency anemia in the etiology of PH and CO has emphasized by numerous researchers since 1960's. However, Walker et al. (2009) opened a discussion by rejecting this etiological explanation. They suggested that iron deficiency anemia, which decreases red blood cell production, cannot be responsible for the marrow hyperplasia that causes PH and CO. According to Walker et al. (2009) the most likely underlying cause of PH and CO, is one of the genetic anemias or an acquired megaloblastic anemia due to B12 and/or folate deficiency. However, Oxenham and Cavill reject this assertion regarding iron-deficiency, and suggest that iron deficiency anemia can produce marrow hyperplasia (Oxenham and Cavill 2010). It was generally accepted that CO share the same etiology with PH. However, recent literature propose a diverse explanation on its etiology, including subperiosteal hematomas due to scurvy and rickets (Ortner 2003; Walker et al. 2009), and megaloblastic anemia (Fairgrieve and Motto 2000; Walker et al. 2009). Although they are not related to marrow hyperplasia, porotic lesions of the cranial vault similar to PH, may also appear in scurvy and rickets. The study sample includes 186 individuals: 58 from Kadikalesi (Kusadasi, Izmir), 43 from Daskyleon (Bandirma), 33 from Smyrna-Agora (Izmir), 27 from Alanya Castle (Antalya), and 25 from Phokaia (Foca, Izmir), all have been dated to Byzantine period. In addition to this sample, the data of 11 skeletal samples from different archaeological sites of Anatolia, which are dated to Roman, Byzantine, Medieval and Post-Medieval periods, were evaluated thoroughly. It attempts to determine how these ancient Anatolian populations were affected by acquired anemias, such as iron deficiency anemia, megaloblastic anemia and genetic anemias, such as thalassemia, sickle-cell anemia and anemia due to G6PD deficiency. The frequencies of PH which have been found in the sample ancient Anatolian populations are as follows: 17.1% in Kadikalesi, 60.9% in Daskyleon, 72.7% in Smyrna-Agora, 35.7% in Alanya Castle, and 30% in Phokaia. On the other hand, the frequencies of CO were 36.8% in Kadikalesi, 27.3% in Daskyleon, 22.2% in Smyrna-Agora, 37.5% in Alanya Castle, and 38.5% in Phokaia. The frequencies of PH and CO were relatively high in these groups. PH was more frequently observed in Daskyleion and Symrna-Agorasi. On the other hand, CO frequencies were higher in Kadikalesi, Alanya Castle and Phokaia. The osseous changes due to genetic anemias were not observed in these samples. The relative high frequencies of PH and CO in these populations seem related to acquired anemias such as iron deficiency and/or megaloblastic anemia due to a multi-factorial origin. The "farming-malaria-thalassemia" thesis could also contribute to the appearance of PH and CO in ancient Anatolian populations, but it is difficult to regard it as a primary cause. In recent studies regarding to anemia in ancient Anatolia, Angel's thesis seem to replaced by acquired iron deficiency anemia approach, which explains it by a multi-factorial origin (Uysal Ugur 1995; Erdal 2000, 2009, 2011; Erdal and Ozbek 2010). However, some researchers suggest that the role of thalassemia in the onset of PH and CO can not be ignored in ancient Anatolia (Asian 2002; Ozbek 2004; Boutin 2008; Erdal 2011). But no cases of thalassemia, with certain diagnosis, have yet been reported in Anatolia. Although their presence is well known in modern Turkey, sickle-cell anemia and anemia due to G6PD deficiency are not considered even as a probable reason in the literature. The common types of anemia seem to be those of acquired anemias in the ancient Anatolian populations as it is the case for today. Although the researchers have mostly emphasized only the effect of iron deficiency anemia, the ancient Anatolians should also been affected by megaloblastic anemia as in modem day. In any case, same conditions lead to iron deficiency anemia and megaloblastic anemia, such as maternal anemia, growing stress, poor nutrition, parasitic and dian-heal infections due to poor sanitation, and premature weaning or prolonged breastfeeding. These factors may also lead to other nutritional deficiencies such as vitamin C and D. As a result, the porotic lesions on the cranial vault or on the orbital roofs, which occurs as a response to iron, vitamin B12 and/or folate, as well as vitamin C and D, are related to poor nutrition and poor sanitation, which are the probable consequences of sedentary life style and increased population density.