Objective: To report a previously undescribed low-O2-affinity hemoglobin variant that is associated with chronic cyanosis.
Design: Pertinent laboratory and historical data for the index case (from Denver, Colorado) and certain family members were recorded, and the hemoglobin variant was characterized.
Material and methods: Electrophoresis, high-performance liquid chromatography (HPLC), and isoelectric focusing were used to examine blood specimens for the presence of hemoglobin variants, and the O2 affinity of whole blood was determined. The abnormal peptide detected on reverse-phase HPLC of separated globin chains was analyzed for its amino acid composition and sequence.
Results: Although no abnormal hemoglobin band separated from hemoglobin A on electrophoresis, HPLC, and isoelectric focusing, a heat test showed hemoglobin instability, and O2 affinity studies disclosed an appreciably right-shifted dissociation curve. On chromatography, the new variant--hemoglobin Denver--was found to be due to a substitution of serine for phenylalanine at position 41 (C7) in the beta chain. In addition to substantial reduction in O2 affinity, hemoglobin Denver is accompanied by moderate reticulocytosis and mild anemia.
Conclusion: Hemoglobin Denver causes no clinical symptoms other than cyanosis, which is attributable to the low O2 affinity.