Fucharoen S, Winichagoon P, Thonglairoam V, Siriboon W, Siritanaratkul N, Kanokpongsakdi S, Vantanasiri C
Thalassemia Center, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand.
Southeast Asian J Trop Med Public Health. 1991 Mar;22(1):16-29.
In this review, we describe a simple strategy to detect the three severe thalassemic diseases commonly found in Thailand. Hb Bart's hydrops fetalis can be detected unambiguously by ultrasonography at 18-20 weeks of gestation or detected early in the first trimester by the gene amplification technique. Prenatal diagnosis for homozygous beta-thalassemia is better performed in the second trimester by in vitro protein synthesis. This is because the molecular defects of some beta-thalassemias are still unknown and homozygosity of the same mutation is low. In contrast, beta-thalassemia/Hb E is easily detected, in the first trimester, by direct visualization on electrophoresis or by dot blot analysis of enzymatically amplified DNA with a set of nonradioactively labeled oligonucleotide probes complementary to the most common mutations. We also found that the beta/gamma synthesis ratio in homozygous Hb E is similar to that of beta-thalassemia/Hb E and DNA analysis is the only method to distinguish these two conditions in the couple at risk of having either beta-thalassemia/Hb E or asymptomatic homozygous Hb E. In 100 pregnancies studied, the diagnoses were achieved in 96 pregnancies. Complications leading to fetal loss were found in 3 pregnancies: one woman developed amnionitis after fetal blood sampling; one had amniotic fluid leakage after the biopsy, and the third, carrying a normal fetus, aborted 10 days after fetal blood sampling with urinary tract infection and high fever. However, these figures are compatible with other reports and the risks are significantly lower than that of thalassemic disease the fetus is facing. One case of beta-thalassemia/Hb E was incorrectly diagnosed prenatally as being Hb E trait. In twenty-five pregnancies (25%) prenatally diagnosed to carry affected fetuses it was decided to have abortion. This study shows the feasibility of prenatal diagnosis for thalassemic diseases in Thailand which, in addition to screening and genetic counseling, can support prevention and control programs for thalassemia.
在本综述中，我们描述了一种简单的策略来检测泰国常见的三种严重地中海贫血疾病。18 - 20周妊娠时，通过超声检查可明确检测出巴氏水肿胎儿型血红蛋白Bart's，或在孕早期通过基因扩增技术进行早期检测。纯合子β地中海贫血的产前诊断在孕中期通过体外蛋白质合成进行效果更佳。这是因为一些β地中海贫血的分子缺陷仍不明确，且相同突变的纯合性较低。相比之下，β地中海贫血/Hb E在孕早期通过电泳直接观察或用一组与最常见突变互补的非放射性标记寡核苷酸探针进行酶促扩增DNA的斑点印迹分析很容易检测出来。我们还发现，纯合子Hb E中的β/γ合成比率与β地中海贫血/Hb E相似，DNA分析是区分这两种情况的唯一方法，对于有患β地中海贫血/Hb E或无症状纯合子Hb E风险的夫妇来说。在研究的100例妊娠中，96例妊娠成功做出诊断。3例妊娠出现导致胎儿丢失的并发症：1名妇女在胎儿采血后发生羊膜炎；1名妇女在活检后羊水渗漏，第3名妇女怀有正常胎儿，在胎儿采血10天后因尿路感染和高烧流产。然而，这些数据与其他报告相符，且风险明显低于胎儿所面临的地中海贫血疾病风险。1例β地中海贫血/Hb E在产前被错误诊断为Hb E性状。在产前诊断为怀有患病胎儿的25例妊娠（25%）中，决定进行流产。本研究表明泰国地中海贫血疾病产前诊断的可行性，这除了筛查和遗传咨询外，还可为地中海贫血的预防和控制项目提供支持。
