HEMOGLOBIN REDONDO [BETA 92(F8) HIS-]ASN] - AN UNSTABLE HEMOGLOBIN-VARIANT ASSOCIATED WITH HEME LOSS WHICH OCCURS IN 2 FORMS

Hb Redondo [beta-92(F8) His --> Asn] illustrates how post-translational structural modifications may modify the phenotypic expression of an unstable hemoglobin. This variant was found in a Portuguese patient suffering from a chronic hemolytic anemia. The electrophoretic pattern demonstrated that it occurred in two forms, both being semi-hemoglobins: the fastest one migrating like HbS and the other like HbA2; after a few days of storage at 4-degrees-C the intensity of the slowest Hb fraction decreased while that of the other increased proportionally. In both cases, the RP-HPLC analysis of the tryptic digest of the aminoethylated beta-chains demonstrated the presence of an abnormal beta-T10 peptide carrying a His --> Asx substitution. Microsequence study of these two peptides demonstrated that the slowest abnormal Hb fraction had a beta-92 His --> Asn substitution and the fastest a His --> Asp at the same site. All these results suggest that the beta-92 His --> Asn variant loses readily its heme group and that a deamidation occurs rapidly in vitro, yielding a beta-92 Asp semi-hemoglobin. The oxygen affinity of the patient's red blood cells was increased, leading to a stimulation of erythropoiesis and to a macrocytic hemolytic disease.