Thalassemia: macroscopic and radiological study of a case

Abstract

Differentiation of the genetic and the acquired anaemias, particularly in areas of the world where they may co-exist, has been a challenge for palaeopathologists for over 100 years. In this paper we present macroscopic and radiographic skeletal lesions that are associated with the thalassemias in a 14-year-old girl from a modern reference collection of the University of Athens. This individual is of known sex, age, cause of death, place and dates of birth and death. The case is examined in terms of epidemiology, growth, distribution and severity of lesions and differential diagnosis. The entire skeleton is affected by marrow hyperplasia: lesions of the axial skeleton are extreme, and the appendicular skeleton is severely affected as well. The odontofacial manifestations that are diagnostic of thalassemia and differentiate it from other anaemias are present and include: maxillary and mandibular hyperplasia, reduced sinuses, displacement of maxillary dental structures, overbite, and generalised osteopenia. The development of extreme bone lesions and the 'advanced' age-at-death of this individual is explained as either the result of thalassemia major under a low transfusion regimen that was the norm during her lifetime, or to a form of thalassemia intermedia that allows survival to later life at the expense of gross skeletal alterations. The present status of skeletal studies in Greece does not support the identification of a genetic anaemia in past populations. The potential contribution of the current analysis in differentiating the anaemias in antiquity is evaluated.

Analysis of the beta-globin gene in DNA of suspected thalassemic great apes

“…The severity of post-cranial skeletal involvement depends on the gravity of the disease and the survival of the individual to it (Moseley, 1965(Moseley, , 1974Hershkovitz et al, 1997;Domrongkitchaiporn et al, 2003;Lagia et al, 2007).…”

“…This information could have aided in understanding the pathogenesis of these abnormalities; in particular, data on the age at death are important in the evaluation of osseous alterations, since in thalassemia, the pattern of the bone involvement may change with advancing age. Especially in the case of isolated skeletons, some authors claim that age should be considered before any assessment of the skeletal pathologies (Moseley 1965(Moseley , 1974Lagia et al, 2007).…”

“…Such osteopathologies have been well described in humans as suggestive of genetic anemias, likely thalassemia (Moseley, 1974;Stuart-Macadam, 1987;Hes et al, 1990;De Mattia et al, 1996;Hollar, 2001;Lagia et al, 2007), but to our knowledge, these cases have never been recorded in non-human primates, with the sole exceptions of Schultz (1956), Nathan andHaas (1966), andDeGusta (2010). While the allelic variants of the β-globin gene associated with thalassemia are very well known in different human ethnic groups (http://omim.org/ entry/141900), no mutations have been reported for the closely related great apes.…”

Morbidity in the marshes: Using spatial epidemiology to investigate skeletal evidence for malaria in Anglo‐Saxon England (AD 410–1050)

“…However, genetic anemia is rare in comparison to acquired anemia. Furthermore, the severity and distribution of the skeletal lesions associated with genetic anemias tend to be much greater than observed in acquired anemia, thus enabling these conditions to be differentiated in the paleopathological record (Hershkovitz et al, 1997;Lagia et al, 2007;Lewis, early view).…”

Porotic hyperostosis in a Late Upper Palaeolithic skeleton (Villabruna 1, Italy)

“…The skull is most severely affected, with outer table erosion, diploic expansion and formation of honeycomb compartments for haematopoietic marrow, leading to the radiographic ''hair-on-end'' appearance. Face and zygoma show an increase in external dimensions, thin cortices and loose spongiosa, resulting in a mongoloid appearance (Ascenzi & Balistreri, 1977;Ortner, 2003;Lagia et al, 2007). T. minor is found in heterozygotes and generally asymptomatic in the skeleton.…”