Harteveld Cornelis L, Groeneveld J H Marc, van Dam Bastiaan, Van Delft Peter, Akkerman Nicole, Arkesteijn Sandra, Giordano Piero C
The Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Hemoglobin. 2005;29(1):11-7.
We describe the characterization of a new hemoglobin (Hb) variant found in a 77-year-old Dutch woman, suspected of hypoxia-mediated erythrocytosis. The typical blood parameters (Hb 17.3 g/dL; PCV 0.525 L/L; RBC 5.82 x 10(12)/L) could not be explained by any of the pathological or physiological conditions causing erythrocytosis. The patient was preventively phlebotomized because of intermittent claudication and erythrocytosis. At the hematological and biochemical levels, no anemia or hemolysis were present and no abnormal Hb fractions were detectable on alkaline electrophoresis or high performance liquid chromatography (HPLC). Molecular analysis revealed intact alpha-globin genes and a heterozygosity for a GTT-->GCT transition at codon 23 of the beta-globin gene, causing a Val-->Ala amino acid substitution. The P50 measured in full blood indicated that this mutant has an elevated oxygen affinity. This is the fourth single nucleotide substitution at codon 23 of the beta gene and the second associated with erythrocytosis. Because the family was not available for investigation no information was obtained as to whether the mutation represents a de novo event or was inherited, and might be a more common cause of erythrocytosis in Dutch patients. Considering the relatively high frequency of beta-thalassemia (thal) in the large allochthonous population in The Netherlands, combinations of Hb Zoeterwoude and beta-thal traits may lead to hemizygosity, with severe hypoxia and erythrocytosis from a few months after birth.
我们描述了在一名77岁荷兰女性中发现的一种新的血红蛋白（Hb）变体的特征，该女性疑似患有缺氧介导的红细胞增多症。典型的血液参数（Hb 17.3 g/dL；PCV 0.525 L/L；RBC 5.82×10¹²/L）无法用任何导致红细胞增多症的病理或生理状况来解释。由于间歇性跛行和红细胞增多症，该患者接受了预防性放血治疗。在血液学和生化水平上，未发现贫血或溶血情况，碱性电泳或高效液相色谱（HPLC）检测也未发现异常的Hb组分。分子分析显示α-珠蛋白基因完整，β-珠蛋白基因第23密码子处存在GTT→GCT转换的杂合性，导致缬氨酸→丙氨酸氨基酸替代。全血中测得的P50表明该突变体具有较高的氧亲和力。这是β基因第23密码子处的第四个单核苷酸替代，也是第二个与红细胞增多症相关的替代。由于无法对该家族进行调查，因此未获得关于该突变是新发事件还是遗传事件的信息，并且它可能是荷兰患者红细胞增多症更常见的原因。考虑到荷兰大量外来人口中β地中海贫血（thal）的相对高发病率，Hb Zoeterwoude和β地中海贫血特征的组合可能导致半合子状态，从出生后几个月起就会出现严重缺氧和红细胞增多症。
