Department of Hematogenetics, ICMR-National Institute of Immunohematology, 13th Floor, K.E.M. Hospital Campus, Parel, Mumbai, 400 012, India.
Department of Hematogenetics, ICMR-National Institute of Immunohematology, 13th Floor, K.E.M. Hospital Campus, Parel, Mumbai, 400 012, India.
Mutat Res Rev Mutat Res. 2021 Jul-Dec;788:108387. doi: 10.1016/j.mrrev.2021.108387. Epub 2021 Jun 10.
There is inconsistency in the exact definition of diagnostic levels of HbA for β thalassemia trait. While many laboratories consider HbA ≥4.0 % diagnostic, still others consider HbA ≥3.3 % or HbA ≥3.5 % as the cut-off for establishing β thalassemia carrier diagnosis. This is because, over the years, studies have described β thalassemia carriers showing HbA levels that lie above the normal range of HbA but below the typical carrier range of β thalassemia. These, "borderline HbA levels", though not detrimental to health, are significant in β thalassemia carrier diagnosis because they can lead to misinterpretation of results. In this review, we have evaluated the prevalence of borderline HbA levels and discussed the causes of borderline HbA values. We have also compiled an extensive catalogue of β globin gene defects associated with borderline HbA levels and have discussed strategies to avoid misdiagnosing borderline HbA β thalassemia carriers. Our analysis of studies that have delineated the cause of borderline HbA levels in different populations shows that 35.4 % [626/1766] of all individuals with borderline HbA levels carry a molecular defect. Among the positive samples, 17 % [299/1766] show β globin gene defects, 7.7 % [137/1766] show α thalassemia defects, 2.7 % [49/1766] show KLF1 gene mutations, 2.3 % [41/1766] show the co-inheritance of β and α thalassemia, 2.0 % [37/1766] show the co-inheritance of β and δ thalassemia and 1.8 % [32/1766] show α globin gene triplication. It appears that a comprehensive molecular work up of the β globin gene is the only definite method to detect borderline HbA β thalassemia carriers, especially in populations with a high prevalence of the disease. The presence of associated genetic or acquired determinants may subsequently be assessed to identify the cause of borderline HbA.
β 地中海贫血特征的诊断性血红蛋白 A（HbA）水平的定义并不一致。虽然许多实验室将 HbA≥4.0%视为诊断标准，但仍有其他实验室将 HbA≥3.3%或 HbA≥3.5%作为确定β 地中海贫血携带者诊断的截止值。这是因为多年来的研究表明，β 地中海贫血携带者的 HbA 水平高于正常 HbA 范围，但低于典型的β 地中海贫血携带者范围。这些“边缘性 HbA 水平”虽然对健康无害，但在β 地中海贫血携带者的诊断中却很重要，因为它们可能导致结果的误读。在这篇综述中，我们评估了边缘性 HbA 水平的流行率，并讨论了边缘性 HbA 值的原因。我们还汇编了一个广泛的β 珠蛋白基因突变目录，这些突变与边缘性 HbA 水平相关，并讨论了避免误诊边缘性 HbAβ 地中海贫血携带者的策略。我们对不同人群中界定边缘性 HbA 水平原因的研究进行分析，结果显示，所有边缘性 HbA 水平个体中有 35.4%[626/1766]携带分子缺陷。在阳性样本中，17%[299/1766]显示β 珠蛋白基因突变，7.7%[137/1766]显示α 地中海贫血缺陷，2.7%[49/1766]显示 KLF1 基因突变，2.3%[41/1766]显示β 和α 地中海贫血的共遗传，2.0%[37/1766]显示β 和δ 地中海贫血的共遗传，1.8%[32/1766]显示α 珠蛋白基因突变。似乎全面的β 珠蛋白基因突变分析是检测边缘性 HbAβ 地中海贫血携带者的唯一明确方法，特别是在疾病高发人群中。随后可以评估相关的遗传或获得性决定因素的存在，以确定边缘性 HbA 的原因。
