SEVERE HEMOLYTIC-ANEMIA ASSOCIATED WITH THE HOMOZYGOUS STATE FOR AN UNSTABLE HEMOGLOBIN-VARIANT (HB BUSHWICK)

We have investigated a 13-year-old girl from first cousin parents who presented with severe hemolytic anemia. Hematologic studies showed uns table hemoglobin (Hb) disease (chronic Heinz body anemia), and DNA ana lysis showed that the patient was homozygous for the previously report ed abnormal Hb called Hb Bushwick (beta(74)E18 gly --> val). Hb Bushwi ck is unstable in vitro and in vivo. In addition, using globin chain b iosynthetic studies, we show that the beta(Bushwick) chains are unstab le. Six members of the patient's family were heterozygous for Hb Bushw ick and had a compensated hemolytic disorder. By contrast, the homozyg ous patient had chronic anemia caused by a combination of hemolysis an d ineffective erythropoiesis that was subject to severe exacerbation c oncomitant with infection. Thus, although unstable Hb disease is corre ctly regarded as dominant, we clearly see a dosage effect in its expre ssion, whereby the homozygous state is still compatible with life alth ough the red blood cells contain nearly 100% unstable Hb. (C) 1995 by The American Society of Hematology.