Hemoglobin Koln Disease in Japan

Hemoglobin Koln disease has been found in eight Japanese families. This department is responsible for the identification of the abnormal hemoglobin in seven of them. Almost all patients have splenomegaly, base line levels of Hb concentration 10-13g/dl, reticulocyte count 4-10% and serum bilirubin 1-2.5mg/dl. MCV is usually normal or slightly increased and MCHC is always smaller than normal, although peripheral blood smear gives an impression of normocytic normochromic erythrocytes. Hb Koln disease may be characterized as a relatively mild chronic hemolytic disorder of autosomal dominant transmission. There may be acute exacerbation of hemolysis in association with ”common cold” etc, however, resulting in drop of Hb concentration to 6 g/dl level, marked reticulocytosis and overt jaundice. Splenectomy is indicated if pancytopenia ensues. Hb Koln can easily be detected by electrophoresis, isopropanol test or heat precipitation method. The ratio of Hb F is at 1% level in most patients, and that of Hb A_2 is usually normal, but can be falsely elevated. The heme-free abnormal β globin is selectively precipitated by PCMB treatment of hemolysate. This precipitate is extremely suitable as a starting material for the study of amino acid substitution. Data on heme loss, subunit dissociation and increased oxygen affinity of Hb Koln have been presented, and the mechanisms of its instability have been explained.