Erythroid marrow activity and functional anemia in patients with the rare interaction of a single functional a-globin and beta-globin gene.
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.
Traeger-Synodinos
J
J
Medical Genetics, Athens University, Aghia Sophia Children's Hospital, Athens, Greece.
Papassotiriou
I
I
Vrettou
C
C
Skarmoutsou
C
C
Stamoulakatou
A
A
Kanavakis
E
E
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
D005914:Globins