Is Hb A(2) elevated in adults with sickle-alpha-thalassemia (beta(s)/beta(s);-alpha/-alpha)?

Thirteen patients with sickle cell anemia (SS) were found to have two alpha gene deletions with a presumptive genotype of beta(s)/beta(s); -alpha/-alpha. Hematological data showed that this group of patients had elevated Hb A(2) level. In order to determine whether the elevation of Hb A(2) is typical of SS with a two alpha gene deletion or is due to undiagnosed S-beta(o)-thalassemia with a two a gene deletion we looked for the presence or absence of beta(o)-thalassemia by molecular techniques. The latter included reverse dot-blot hybridization to rule out a beta-thalassemia mutation, digestion with Cvnl endonuclease followed by Southern blotting and hybridization with a beta genomic probe, and, in selected patients, determination of the synthetic alpha/beta ratio. One of the 13 patients had S-beta(o)-thalassemia with a G-->A mutation at IVS-II-1 indicating that her genotype was beta(s)/beta(o) thalassemia; -alpha/-alpha. The remaining 12 patients were homozygous for the sickle gene, had relatively elevated Hb levels, increased Hb A(2) values, and Hb F levels similar to those in patients with SS and four or three alpha genes. At the clinical level, the 12 patients with SS and a two alpha 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 alpha gene deletion (beta(s)/beta(s); -alpha/-alpha) is a unique subset of patients with SS characterized by distinct hematological and clinical features.