Homozygous HbC gene results only in mild hemolytic anemia. In HbSC disease red cells contain equal levels of HbS and HbC. It is a paradox that HbSC exhibit a moderately severe phenotype in spite of being a mixture of HbS trait and HbC trait, neither of which has significant pathology. Why does the combination of these two Hbs result in a serious disease? The short answer is that HbC enhances, by dehydrating the SC red cell, the pathogenic properties of HbS, resulting in a clinically significant disorder, but somewhat milder that sickle cell anemia (SCA). Nevertheless, retinnitis proliferans, osteonecrosis, and acute chest syndrome have equal or higher incidence in HbSC disease compared to SCA. This pathogenic trick is accomplished by HbC inducing, by mechanisms not fully understood, an increase in the activity of K:Cl cotransport that induces the lost of K(+) and consequently of intracellular water. This event creates a sufficient increase of MCHC, so that the lower levels of HbS found in SC red cells can polymerize rapidly and effectively. This situation offers a unique opportunity: if we could inhibit the effect of HbC on K(+) transport we can cure the disease.

中文翻译：

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血红蛋白SC病的悖论。

纯合子HbC基因仅导致轻度溶血性贫血。在HbSC疾病中，红细胞含有相等水平的HbS和HbC。尽管HbS性状和HbC性状混合在一起，但两者均无明显病理，HbSC仍表现出中等严重的表型是一个悖论。这两种Hb的组合为什么会导致严重的疾病？简短的答案是，HbC通过使SC红细胞脱水而增强HbS的致病特性，导致临床上显着的疾病，但比镰状细胞性贫血（SCA）轻一些。然而，与SCA相比，增殖性视网膜炎，骨坏死和急性胸综合症在HbSC疾病中的发病率相同或更高。通过不完全了解的机制，HbC诱导K活性增加，从而实现了这种致病性技巧：Cl共同运输，导致K（+）丢失，从而导致细胞内水丢失。此事件使MCHC充分增加，因此SC红细胞中发现的较低水平的HbS可以快速有效地聚合。这种情况提供了一个独特的机会：如果我们可以抑制HbC对K（+）转运的作用，就可以治愈该疾病。