HEMOGLOBIN DENVER [ALPHA(2)BETA(2)41 (C7) PHE-]SER] - A LOW-O-2-AFFINITY VARIANT ASSOCIATED WITH CHRONIC CYANOSIS AND ANEMIA

Objective: To report a previously undescribed low-O-2-affinity hembglo bin variant that is associated with chronic cyanosis. Design: Pertinen t laboratory and historical data for the index case (from Denver, Colo rado) and certain family members were recorded, and the hemoglobin var iant was characterized. Material and Methods: Electrophoresis, high-pe rformance liquid chromatography (HPLC), and isoelectric focusing were used to examine blood specimens for the presence of hemoglobin variant s, and the O-2 affinity of whole blood was determined. The abnormal pe ptide detected on reverse-phase HPLC of separated globin chains was an alyzed for its amino acid composition and sequence. Results: Although no abnormal hemoglobin band separated from hemoglobin A on electrophor esis, HPLC, and isoelectric focusing, a heat test showed hemoglobin in stability, and O-2 affinity studies disclosed an appreciably right-shi fted dissociation curve. On chromatography, the new variant-hemoglobin Denver-was found to be due to a substitution of serine for phenylalan ine at position 41 (C7) in the beta chain. In addition to substantial reduction in O-2 affinity, hemoglobin Denver is accompanied by moderat e reticulocytosis and mild anemia. Conclusion: Hemoglobin Denver cause s no clinical symptoms other than cyanosis, which is attributable to t he low O-2 affinity.