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 ha d 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 t o undiagnosed S-beta(o)-thalassemia with a two a gene deletion we look ed for the presence or absence of beta(o)-thalassemia by molecular tec hniques. The latter included reverse dot-blot hybridization to rule ou t a beta-thalassemia mutation, digestion with Cvnl endonuclease follow ed by Southern blotting and hybridization with a beta genomic probe, a nd, in selected patients, determination of the synthetic alpha/beta ra tio. One of the 13 patients had S-beta(o)-thalassemia with a G-->A mut ation at IVS-II-1 indicating that her genotype was beta(s)/beta(o) tha lassemia; -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 ne crosis, retinopathy, and splenomegaly, but decreased prevalence of leg ulcers and cerebrovascular accidents. Together, the data indicate tha t SS with a two alpha gene deletion (beta(s)/beta(s); -alpha/-alpha) i s a unique subset of patients with SS characterized by distinct hemato logical and clinical features.