Powars D, Hiti A
Department of Pediatrics, University of Southern California, Los Angeles 90033.
Am J Dis Child. 1993 Nov;147(11):1197-202. doi: 10.1001/archpedi.1993.02160350071011.
Identification of the beta s gene cluster haplotype and alpha-gene status provides a useful tool for the detection of high-risk patients with sickle cell anemia. Analysis of the relationship of the long-term clinical course to the above parameters has revealed that those with the haplotype designated Senegal have decreased severity, those with the Benin haplotype have intermediate severity, and those with the Central African Republic (CAR) haplotype have the most severe clinical expression. Further modulation of the clinical course occurs with the coinheritance of alpha-thalassemia-2. In both Africa and the United States, the CAR beta s haplotype increased the risk (relative risk, 2.25; 95% confidence interval, 1.41 to 3.87) of developing a complication and death at an early age. Detection of the CAR haplotype identifies the child with sickle cell anemia at risk for a rapid rate of progression of sickle-induced microvasculopathy, ultimately leading to irreversible organ damage during the first three decades of life. In patients with the CAR haplotype, potential curative therapy, such as bone marrow transplantation or gene insertion, should be seriously considered during childhood, before organ failure is clinically evident.
βS基因簇单倍型和α基因状态的鉴定为镰状细胞贫血高危患者的检测提供了一种有用的工具。对长期临床病程与上述参数之间关系的分析表明，具有塞内加尔单倍型的患者病情严重程度降低，具有贝宁单倍型的患者病情严重程度中等，而具有中非共和国（CAR）单倍型的患者临床表型最为严重。α地中海贫血-2的共同遗传会进一步调节临床病程。在非洲和美国，CAR βS单倍型均增加了早年发生并发症和死亡的风险（相对风险为2.25；95%置信区间为1.41至3.87）。检测到CAR单倍型可识别出患有镰状细胞贫血且有镰状细胞诱导的微血管病变快速进展风险的儿童，最终在生命的前三十年导致不可逆的器官损伤。对于具有CAR单倍型的患者，在儿童期、临床出现器官衰竭之前，应认真考虑进行潜在的治愈性治疗，如骨髓移植或基因插入。
