Hemoglobin Savannah (B6(24) beta-glycine is greater than valine): an unstable variant causing anemia with inclusion bodies

• Published in: The Journal of clinical investigation 1971-03, Vol.50 (3), p.650-659
• Main Authors: Huisman, T H, Brown, A K, Efremov, G D, Wilson, J B, Reynolds, C A, Uy, R, Smith, L L
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acids - analysis; Anemia, Hemolytic, Congenital Nonspherocytic - blood; Anemia, Hemolytic, Congenital Nonspherocytic - etiology; Blood Protein Electrophoresis; Chemical Phenomena; Chemistry; Chromatography, DEAE-Cellulose
• ISSN: 0021-9738
• DOI: 10.1172/JCI106535

An abnormal hemoglobin, termed Hb Savannah, was found in red cell hemolysate of a young Caucasian girl with severe hemolytic anemia. The presence of this unstable variant became evident when inclusion bodies appeared rapidly upon exposure of red cells to redox dyes and a large percentage of hemoglobin in hemolysate precipitated on warming to 65 degrees C. Treatment of the hemoglobin with p-hydroxymercuribenzoate (PMB) caused a rapid dissociation into monomers; starch-gel electrophoresis of PMB-treated hemoglobin showed the presence of abnormal beta-chains. Data from structural studies of isolated beta-chains indicated substitution of a valyl residue for the normally occurring glycyl residue at position 24, which corresponds to helical residue B6. A similar substitution but with an arginine replacing the glycyl residue has been observed in Hb Riverdale-Bronx. The glycine to valine substitution will change the relationship of the B and the E helices which results in extensive conformational changes in the beta-chain. This change presumably causes an increased dissociation of the hemoglobin molecule into dimers and probably monomers, and a decreased stability of the alphabeta-dimers. The hemoglobin abnormality may be the result of a fresh mutation because the abnormality is not present in the parents nor in any of the seven siblings.