Severe hemolytic anemia associated with the homozygous state for an unstable hemoglobin variant (Hb Bushwick)

• Published in: Blood 1995-09, Vol.86 (5), p.1977-1982
• Main Authors: SRIVASTAVA, P, KAEDA, J. S, ROPER, D, VULLIAMY, T. J, BUCKLEY, M, LUZZATTO, L
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anemia, Hemolytic - blood; Anemia, Hemolytic - genetics; Anemias. Hemoglobinopathies; Base Sequence; Basophils - pathology; Biological and medical sciences; Child; Consanguinity; Diseases of red blood cells; DNA Primers; Exons; Female; Genetic Variation; Globins - genetics; Glycine; Hematologic and hematopoietic diseases; Hemoglobins, Abnormal - genetics; Homozygote; Humans; Introns; Male; Medical sciences; Molecular Sequence Data; Pedigree; Point Mutation; Polymerase Chain Reaction; Valine
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V86.5.1977.bloodjournal8651977

We have investigated a 13-year-old girl from first cousin parents who presented with severe hemolytic anemia. Hematologic studies showed unstable hemoglobin (Hb) disease (chronic Heinz body anemia), and DNA analysis showed that the patient was homozygous for the previously reported abnormal Hb called Hb Bushwick (beta 74E18 gly-->val). Hb Bushwick is unstable in vitro and in vivo. In addition, using globin chain biosynthetic studies, we show that the beta (Bushwick) chains are unstable. Six members of the patient's family were heterozygous for Hb Bushwick and had a compensated hemolytic disorder. By contrast, the homozygous patient had chronic anemia caused by a combination of hemolysis and ineffective erythropoiesis that was subject to severe exacerbation concomitant with infection. Thus, although unstable Hb disease is correctly regarded as dominant, we clearly see a dosage effect in its expression, whereby the homozygous state is still compatible with life although the red blood cells contain nearly 100% unstable Hb.