Very mild forms of Hb S/beta+-thalassemia in Brazilian children

The clinical phenotype of sickle cell/beta+-thalassemia (Hb S/ +-Thal) is highly variable, and severity is associated with the quantitative degree of decrease in the production of the beta globin chains.1 Evidence shows that differences in the production of hemoglobin A (Hb A) and severity correspond to different molecular beta-thalassemia ( -Thal) mutations.2 A previous report proposed a classification of Hb S/ +-Thal phenotypes based on the relative concentration of Hb A: Type I: 1–7% of Hb A; Type II: 7–14% of Hb A; and Type III: 14–25% of Hb A.2 However, some -Thal mutations lead to low impairment of -globin production and the resulting phenotype does not fit this proposed classification. In a single patient case report, the −92 (C>T) mutation was associated with a high level of Hb A (45%) in an adult Sicilian patient with Hb S/ +-Thal.3 Recently, a combination of two sequence variants, IVS-II839 (T>C) and IVS-II-844 (C>A), was associated with a very mild phenotype of sickle cell disease (SCD).4 Because of the marked clinical variability of Hb S/ +-Thal patients, molecular