胎儿血红蛋白 Bart's 对评估胎儿 α-地中海贫血综合征的诊断价值：应用于未诊断的α-血红蛋白病引起的胎儿贫血的产前特征。

Diagnostic value of fetal hemoglobin Bart's for evaluation of fetal α-thalassemia syndromes: application to prenatal characterization of fetal anemia caused by undiagnosed α-hemoglobinopathy.

机构信息

Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.

Faculty of Medicine, Mahasarakham University, Mahasarakham, Thailand.

出版信息

Orphanet J Rare Dis. 2022 Feb 10;17(1):45. doi: 10.1186/s13023-022-02197-w.

DOI:10.1186/s13023-022-02197-w

PMID:35144630

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8832766/

Abstract

BACKGROUND

To evaluate whether the quantification of fetal hemoglobin (Hb) Bart's is useful for differentiation of α-thalassemia syndromes in the fetus and to characterize the fetal anemia associated with fetal α-hemoglobinopathy.

METHODS

A total of 332 fetal blood specimens collected by cordocentesis were analyzed using capillary electrophoresis and the amount of Hb Bart's was recorded. The result was evaluated against thalassemia genotypes determined based on Hb and DNA analyses. Prenatal Hb and DNA characterization of the fetal anemia observed in two families was done.

RESULTS

Among 332 fetuses investigated, Hb and DNA analyses identified 152 fetuses with normal genotypes. The remaining 180 fetuses carried α-thalassemia with several genotypes. Variable amounts of Hb Bart's were identified in all fetuses with α-thalassemia, which could be used for simple differentiation of fetal α-thalassemia genotypes. These included α- and α-thalassemia traits, homozygous α-thalassemia and Hb Constant Spring (CS), Hb H disease, Hb H-CS and Hb H-Quong Sze diseases, homozygous α-thalassemia causing the Hb Bart's hydrops fetalis and a remain uncharacterized α-thalassemia defect. The previously undescribed interactions of Hb Queens Park and Hb Amsterdam A1 with Hb E were detected in two fetuses with Hb Bart's of 0.5%. The Hb Queens Park-AEBart's disease was also noted in one pregnant woman. Prenatal analysis of the fetuses with severe fetal anemia and cardiomegaly with Hb Bart's of 9.0% and 13.6% revealed unexpectedly the homozygous Hb CS and a compound heterozygosity of Hb CS/Hb Pakse' with Hb E heterozygote, respectively.

CONCLUSIONS

The usefulness of detecting and differentiation of fetal α-thalassemia syndromes by quantifying of Hb Bart's was demonstrated. Apart from the fatal condition of Hb Bart's hydrops fetalis associated with homozygous α-thalassemia, homozygous Hb CS and a compound Hb CS/Hb Pakse' could result in severe fetal anemia and fetal complications, prenatal diagnosis is highly recommended. The simple Hb Bart's quantification of fetal blood should prove helpful in this matter.

摘要

背景

评估胎儿血红蛋白（Hb）Bart's 的定量是否有助于区分胎儿的α-地中海贫血综合征，并描述与胎儿α-血红蛋白病相关的胎儿贫血。

方法

对 332 例通过脐带穿刺采集的胎儿血标本进行毛细管电泳分析，并记录 HbBart's 的含量。根据 Hb 和 DNA 分析确定的地中海贫血基因型对结果进行评估。对两个家系中观察到的胎儿贫血进行产前 Hb 和 DNA 特征分析。

结果

在 332 例受检胎儿中，Hb 和 DNA 分析确定 152 例胎儿基因型正常。其余 180 例胎儿携带α-地中海贫血，基因型多样。所有携带α-地中海贫血的胎儿均检出不同量的 HbBart's，可用于简单区分胎儿α-地中海贫血基因型。这些基因型包括α-和α+地中海贫血、纯合子α-地中海贫血和 Hb Constant Spring（CS）、Hb H 病、Hb H-CS 和 Hb H-Quong Sze 病、导致 HbBart's 胎儿水肿的纯合子α-地中海贫血以及尚未明确的α-地中海贫血缺陷。在 2 例 HbBart's 为 0.5%的胎儿中检测到了以前未描述的 Hb Queens Park 和 Hb Amsterdam A1 与 Hb E 的相互作用。在 1 名孕妇中还发现了 Hb Queens Park-AE Bart's 病。对 HbBart's 为 9.0%和 13.6%的严重胎儿贫血和心脏肿大胎儿进行产前分析，出人意料地发现了纯合子 Hb CS 和 Hb CS/Hb Pakse 与 Hb E 杂合子的复合杂合子。

结论

通过定量检测 HbBart's 证明了检测和区分胎儿α-地中海贫血综合征的有效性。除了与纯合子α-地中海贫血相关的 HbBart's 胎儿水肿不良预后外，纯合子 Hb CS 和 Hb CS/Hb Pakse 也可能导致严重的胎儿贫血和胎儿并发症，强烈建议进行产前诊断。简单的胎儿血 HbBart's 定量分析在这方面应该会有所帮助。