title: Erythroid marrow activity and functional anemia in patients with the rare interaction of a single functional a-globin and beta-globin gene.
abstract: OBJECTIVE
  The degree of globin chain imbalance and tissue hypoxia are important determinants of clinical severity in thalassemia syndromes. Thus phenotypic expression may be modified by interaction of alpha- and beta-thalassemia defects, level and type of hemoglobin synthesized and oxygen release to the tissues. We evaluated hematology, erythroid marrow activity and functional anemia in patients with the rare interaction of a single a-globin gene and heterozygous beta-thalassemia (HbH/beta-thal trait).
  
  
  METHODS
  In 7 patients characterized by DNA analysis to have HbH disease genotypes with beta-thalassemia trait, we assessed hematologic findings, serum transferrin receptor (sTfR), serum erythropoietin (Epo), red cell 2,3-disphosphoglycerate (2,3-DPG) and whole blood oxygen releasing capability.
  
  
  RESULTS
  Patients with HbH/beta-thal trait had moderate anemia, marked hypochromasia and microcytosis, normal or raised HbA2, and no electrophoretically/chromatographically detectable HbH. Epo and sTfR levels were significantly higher than in beta-thalassemia heterozygotes, but lower than in patients with HbH disease; 2,3-DPG levels were highest in HbH/beta-thal trait. Oxygen binding studies and simulations showed reduced oxygen affinity (P50) in HbH/beta-thal trait, resulting in increased oxygen release (O2R).
  
  
  CONCLUSIONS
  Hematologic findings and bone marrow activity in patients with HbH/b-thal trait were consistent with the modified globin chain imbalance and hemoglobin synthesis expected from interaction of HbH disease with heterozygous b-thalassemia, although this rare complex genotype may elude diagnosis based on hematology alone. Significantly higher red cell 2,3-DPG levels were an unexpected finding, and the consequent increase in oxygen release capability resulted in a compensated functional anemia relative to hemoglobin levels.
authors.affiliation: Medical Genetics, Athens University, Aghia Sophia Children's Hospital, Athens, Greece.
authors.forename: J
authors.initials: J
authors.lastname: Traeger-Synodinos
authors.forename: I
authors.initials: I
authors.lastname: Papassotiriou
authors.forename: C
authors.initials: C
authors.lastname: Vrettou
authors.forename: C
authors.initials: C
authors.lastname: Skarmoutsou
authors.forename: A
authors.initials: A
authors.lastname: Stamoulakatou
authors.forename: E
authors.initials: E
authors.lastname: Kanavakis
mesh_terms: D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000097:blood / Q000209:etiology; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D005838:Genotype; D005914:Globins / Q000235:genetics* / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D012156:Reticulocytes / Q000378:metabolism*; D017085:alpha-Thalassemia / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics / Q000473:pathology
chemical_list: D005914:Globins