Pathophysiology and Clinical Manifestations of the  -Thalassemias

Abstract

The b-thalassemia syndromes reflect deficient or absent b-globin synthesis usually owing to a mutation in the b-globin locus. The relative excess of a-globin results in the formation of insoluble aggregates leading to ineffective erythropoiesis and shortened red cell survival. A relatively high capacity for fetal hemoglobin synthesis is a major genetic modifier of disease severity, with polymorphisms in other genes also having a significant role. Iron overload secondary to enhanced absorption and red cell transfusions causes an increase in liver iron and in various other tissues, leading to endocrine and cardiac dysfunction. Modern chelation regimens are effective in removing iron and preserving or restoring organ function.

Orodental Considerations in Thalassemia Patients

“…Iron deposition in the parenchymal tissues of thalassemia patients can be observed within a year of the onset of regular blood transfusions [33]. Studies have shown that iron gets accumulated in the cardiac, endocrine, hepatic tissues and gingivae of thalassemia major patients [34,35]. While the impact of iron deposits on periodontal health is unidentified, more studies investigating the use of gingival biopsies for the diagnosis of iron overload are required.…”

The Role of the Inherited Disorders of Hemoglobin, the First “Molecular Diseases,” in the Future of Human Genetics

“…And after many years of failure, promising approaches to somatic cell gene therapy for thalassemia have been reported, and trials are likely in the near future. It is beyond the scope of this article to review these issues in detail, several of which have been the subject of recent reviews (41,62,63,97).…”

Classification of the Disorders of Hemoglobin

“…Moreover, a-and non-a-globin synthesis must be closely matched. As explained in Nienhuis and Nathan (2012), subunit imbalance is central to the pathophysiologyof the thalassemias. Free a-globin subunits are particularly toxic to erythroid cells.…”