Faculty of Medicine, Department of Pediatrics and Thalassemia Center, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Clin Chem Lab Med. 2013 Aug;51(8):1605-14. doi: 10.1515/cclm-2013-0098.
Prevention and control of severe β thalassemia by carrier detection and identification of couples at risk in developed countries is one of the most successful stories in modern medicine. Similar programs in developing countries especially Southeast Asia, are more problematic because both α and β thalassemias are highly prevalent. In Thailand, there are limited data on whether we could determine, based on hematological phenotypes, the mutation severity and/or coinheritance of α thalassemia in β thalassemia traits.
Comprehensive molecular, hematology and hemoglobin analyses of the α and β globin genes were performed in 141 healthy individuals identified as β thalassemia carriers.
Seventeen different β globin mutations were successfully identified out of all cases analyzed. Although the majority of the mutations identified were the β⁰ or severe β⁺ thalassemia alleles, a high proportion of mild mutations (25%) was observed. Of these β thalassemia traits, 22.3% were found to co-inherit the α thalassemias. Milder hematological phenotypes were noted in β⁺ compared with β⁰ thalassemia traits when the α globin genes were intact. Although co-inheritance of α⁰ thalassemia might be suspected in cases with skewed profiles, due to the overlapping values, it remains difficult to apply these parameters for reliable carrier determination.
A combination of hemoglobin analysis and DNA testing seems to be the best way to confirm carrier status in a region with high frequency for both α and β thalassemias. Underdiagnoses of carrier status could hamper the effectiveness of a thalassemia prevention and control program.
在发达国家，通过对携带者的检测和风险夫妇的识别来预防和控制重型β地中海贫血，是现代医学最成功的故事之一。在发展中国家，特别是东南亚国家，类似的计划存在更多问题，因为α和β地中海贫血都非常普遍。在泰国，基于血液学表型，我们能否确定β地中海贫血表型中α地中海贫血的突变严重程度和/或共遗传，相关数据有限。
对 141 名被鉴定为β地中海贫血携带者的健康个体进行了全面的α和β珠蛋白基因分子、血液学和血红蛋白分析。
在所分析的所有病例中，成功鉴定出 17 种不同的β珠蛋白突变。虽然鉴定出的大多数突变是β⁰或严重的β⁺地中海贫血等位基因，但观察到轻度突变的比例很高（25%）。在这些β地中海贫血表型中，发现 22.3%的个体同时共遗传了α地中海贫血。当α珠蛋白基因完整时，β⁺地中海贫血表型的血液学表型比β⁰地中海贫血表型更轻。尽管由于重叠值，可能会怀疑存在α⁰地中海贫血的共遗传，但由于这些参数难以用于可靠的携带者确定，因此仍难以应用这些参数。
在同时存在高频率α和β地中海贫血的地区，血红蛋白分析和 DNA 检测的结合似乎是确认携带者状态的最佳方法。携带者状态的漏诊可能会影响地中海贫血的预防和控制计划的有效性。
