Is Hb A2 Elevated in Adults with Sickle-A-Thalassemi (βS/βS; -α/-α)

Thirteen patients with sickle cell anemia (SS) were found to have two a gene deletions with a presumptive genotype of βs/βs; -α/-α. Hematological data showed that this group of patients had elevated Hb A2 level. in order to determine whether the elevation of Hb A2 is typical of SS with a two α gene deletion or is due to undiagnosed S-β°-thalassemia with a two a gene deletion we looked for the presence or absence of β°-thalassemia by molecular techniques. The latter included reverse dot-blot hybridization to rule out a β-thalassemia mutation, digestion with Cvn endonuclease followed by Southern blotting and hybridization with a β genomic probe, and, in selected patients, determination of the synthetic α/β ratio. One of the 13 patients had S-β°-thalassemia with a G→A mutation at IVS-11-1 indicating that her genotype was βs/β° thalassemia; -α/-α. The remaining 12 patients were homozygous for the sickle gene, had relatively elevated Hb levels, increased Hb A2 values, and Hb F levels similar to those in patients with SS and four or three α genes. At the clinical level, the 12 patients with SS and a two α gene deletion had increased prevalence of avascular necrosis, retinopathy, and splenomegaly, but decreased prevalence of leg ulcers and cerebrovascular accidents. Together, the data indicate that SS with a two a gene deletion (βs/βs; -α/α) is a unique subset of patients with SS characterized by distinct hematological and clinical features.