Traeger-Synodinos J, Papassotiriou I, Vrettou C, Skarmoutsou C, Stamoulakatou A, Kanavakis E
Medical Genetics, Athens University, Aghia Sophia Children's Hospital, Athens, Greece.
Haematologica. 2001 Apr;86(4):363-7.
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).
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.
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).
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.
珠蛋白链失衡程度和组织缺氧是地中海贫血综合征临床严重程度的重要决定因素。因此，α和β地中海贫血缺陷的相互作用、合成的血红蛋白水平和类型以及向组织的氧释放可能会改变表型表达。我们评估了单个α珠蛋白基因与杂合β地中海贫血（HbH/β地中海贫血特征）罕见相互作用患者的血液学、红系骨髓活性和功能性贫血。
对7例经DNA分析具有HbH病基因型和β地中海贫血特征的患者，我们评估了血液学检查结果、血清转铁蛋白受体（sTfR）、血清促红细胞生成素（Epo）、红细胞2,3 - 二磷酸甘油酸（2,3 - DPG）和全血氧释放能力。
HbH/β地中海贫血特征患者有中度贫血、明显低色素血症和小红细胞症，HbA2正常或升高，且电泳/色谱法未检测到HbH。Epo和sTfR水平显著高于β地中海贫血杂合子，但低于HbH病患者；2,3 - DPG水平在HbH/β地中海贫血特征患者中最高。氧结合研究和模拟显示HbH/β地中海贫血特征患者的氧亲和力（P50）降低，导致氧释放（O2R）增加。
HbH/β地中海贫血特征患者的血液学检查结果和骨髓活性与HbH病与杂合β地中海贫血相互作用预期的珠蛋白链失衡和血红蛋白合成改变一致，尽管这种罕见的复杂基因型可能仅靠血液学难以诊断。红细胞2,3 - DPG水平显著升高是一个意外发现，由此导致的氧释放能力增加相对于血红蛋白水平导致了代偿性功能性贫血。
