Nancy F. Olivieri

Whereas hemoglobin (Hb) E-beta thalassemia is recognized as probably the most common serious hemoglobinopathy worldwide, its natural history remains poorly defined. The interaction of hemoglobin E and beta-thalassemia result in a wide spectrum of clinical disorders, some indistinguishable from thalassemia major and some milder and not transfusion-dependent. Partially as a result of this wide range of phenotypes, clear guidelines for approaches to transfusion and to iron-chelating therapy for patients with Hb E-beta thalassemia have not been developed. By contrast, data that have accumulated during the past 10 years in patients with beta-thalassemia permit a quantitative approach to the management of iron overload and provide guidelines for the control of body iron burden in individual patients treated with iron-chelating therapy. These guidelines may be applicable to patients with Hb E-beta thalassemia. Preliminary evidence from our studies of iron loading in affected patients with Hb E-beta thalassemia in Sri Lanka suggest that this disorder may be associated with variable, but accelerated, gastrointestinal iron absorption, and that the iron loading associated with chronic transfusions in patients with Hb E-beta thalassemia is similar to that observed in patients with beta-thalassemia. These data, in the only cohort of patients with Hb E-beta thalassemia to have undergone quantitative assessment of body iron burden, suggest that the principles that guide assessment of iron loading and initiation of chelating therapy in patients with beta-thalassemia may be generally applicable to those with Hb E-beta thalassemia. Further quantitative studies in both nontransfused and transfused patients will be necessary to permit firm conclusions.

In 1925, Thomas Cooley and Pearl Lee described a form of severe anemia, occurring in children of Italian origin and associated with splenomegaly and characteristic bone changes.¹ Over the next decade, a milder form was described independently by several Italian investigators.²⁴ Because all early cases were reported in children of Mediterranean origin, the disease was later termed thalassemia, from the Greek word for sea, thalassa.⁵ Over the next 20 years, it became apparent that Cooley and Lee had described the homozygous or compound heterozygous state for a recessive mendelian disorder not confined to the Mediterranean, but occurring widely . . .