镰刀形红细胞贫血症（Sickle Cell Anemia）是一种常染色体隐性基因遗传病。患病者的血液红细胞表现为镰刀状，其携带氧的功能只有正常红细胞的一半。现在医生可以用regular blood transfusion避开伤害患者的大脑来阻止这类疾病的发病，但是，迄今为止还没有能真正治愈的药物。 血红蛋白分子结构异常的遗传性疾病，主要症状是贫血。病人衰弱、头晕、气短、心脏有杂音和脉搏增高；血液血红蛋白（Hb）含量仅及正常人（每100毫升血15～16克）的一半；红细胞不仅数量少而且异常；出现许多长而薄，看起来像镰刀的新月形红细胞。 当血液脱氧合（不携氧）时，镰刀形细胞大大增多。这种细胞极脆，易破损造成血液血红蛋白低水平。更严重的后果是某些器官的毛细血管被这些长形异常细胞堵塞，这是许多镰刀形红细胞贫血症病人早死的主要原因。镰刀形红细胞贫血病是从双亲处接受Hb突变基因的一种遗传病。只从父母一方得到此异常基因，则仅有约1%的红细胞镰刀形化，这种人只有轻微的镰刀形红细胞贫血症症状，如避免强烈的运动或其他使循环系统紧张的状态，可过完全正常的生活。镰刀形红细胞贫血症是一种“分子病”，即分子结构、特别是蛋白质分子结构发生遗传性变化而造成的病变。异常血红蛋白β链的第6位谷氨酸被缬氨酸所代替。这个疏水氨基酸正好适合另一血红蛋白分子β链EF角上的“口袋”，这使两条血红蛋白链互相“锁”在一起，最终与其他血红蛋白链共同形成一个不溶的长柱形螺旋纤维束，使红细胞扭旋成镰刀形。至于为什么脱氧合血红蛋白镰刀形化而氧合血红蛋白（携氧）不镰刀形化？可以简单解释为：在氧合形式中，血红蛋白亚基的重新排列使β链的口袋不能接受相邻的血红蛋白分子。 镰刀形细胞性贫血症由β链基因点突变引起 该病的主要原因是因为珠蛋白的β基因发生单一碱基突变,正常β基因的第6位密码子为GAG,编码谷氨酸,突变后为GTG,编码缬氨酸,使成为HbS.在纯合子状态,当形成HbS后,HbS在脱氧状态下聚集成多聚体,因形成的多聚体排列方向与膜平行,与细胞膜的接触又非常紧密,所以当多聚体达到一定量时,细胞膜便由正常的双凹形盘状变成镰刀形.该细胞僵硬,变形性差,易破而溶血,造成血管阻塞,组织缺氧,损伤,坏死.在杂纯合子状态,镰刀状细胞则是由HbS,HbA杂合而成.患者从父母继承了一个正常的 β基因和一个异常的β基因,与α组成HbS.这种患者HbS占20%~45%,其余为HsA.患者平时往往无症状,因HbS浓度低在一般情况下细胞并不变形.然而在特殊缺氧条件下,红细胞可能发生镰变,此类型往往不需要治疗,但应避免高山等缺氧环境. 镰刀形细胞性贫血症的基因诊断可采用PCR-限制性内切酶谱分析法,先用PCR从患者基因组DNA扩增含突变位点的珠蛋白基因片段,再选择适当的限制性内切酶水解PCR产物,根据酶切产物在电泳图谱上的片段数量和大小做出判断.也可与特意的寡核苷酸探针进行Southern印记杂交分析,根据杂交图谱做出判断. 该病目前没有特效治疗手段,主要靠输血维持,患者多在成年前死亡.此外就是应用基因诊断做出产前诊断,降低发病率.该病在美国黑人中发病率达14%. 1 通过移植另外一个人的健康的造血干细胞来治愈。但是这种方法对那些很难找到一个相容性供者的人来说就没有用了。 2 为了治疗镰刀形细胞贫血症, Sloan-Kettering的科学家们发明了一种新的工程性策略，通过结合RNA干扰以及球蛋白转基因技术创造出一种治疗性的转基因。这种新基因有两个功能：产生正常的血红蛋白和抑止镰刀形血红蛋白的形成。治疗性的基因被导入病毒载体并转化入造血干细胞。细胞接受这种处理后，便能产生正常的血红蛋白。 3 一氧化氮或可减轻镰刀形红细胞贫血症患者痛感 吸入一氧化氮（NO）气体，也许能减轻镰刀形红细胞贫血症患者的痛感。这是美国科学家最新研究成果，但仍需进一步人体临床试验。 镰刀形红细胞贫血症是一种遗传性疾病，主要由人体内合成血红蛋白的基因突变引起。其一奇怪特征是，血液中的红细胞会由正常的圆形变成镰刀状。医学界传统观念认为，变形的红细胞会堵塞血管，使血液和氧供应量减少，造成了溶血性贫血，并导致患者关节、四肢等部位周期性地感觉剧痛。 美国国家卫生研究所格拉德温等人的最新研究发现，对这种痛感起重要作用的可能还有由变形红细胞释放进入血液的血红蛋白。血红蛋白存在于极易碎裂的红细胞中，其功能是运送氧到血液中去。研究人员发现，当这些血红蛋白以自由状态进入血液循环后，其与一氧化氮产生反应的速度，将比在红细胞中时快出上千倍，一氧化氮因此而被过度“清除”。 格拉德温等人10日在网络版《自然医学》杂志发表论文指出，一氧化氮能够通过松弛血管而调节血压，当它被自由循环的血红蛋白“清除”后，血管可能产生不必要的收缩，从而进一步加重患者的病痛。 这一新结果意味着，吸入一氧化氮气体，也许可以缓解镰刀形红细胞贫血症患者的痛感。 Sickle cell disease is caused by the substitution of a single amino acid in the hemoglobin protein of red blood cells. When the oxygen content of an affected individual's blood is low(at high altitudes or under physical stree, for instance), the sickle cell hemolgobin molecules crystallize by aggregating into long rods. the crystals deform the red cells into a sickle shape. Sickling of the cells, in turn, can lead to other symptoms. The mutliple effects of a double does of the sickle cell allele are an example of pleiotropy. The non-sickle cell counterpart of the sickle cell allele is in fact only incompletely dominant to the sickle cell allele at the level of the organism. Heterozygotes--carriers of a single sickle cell allele--are said to have sickle cell trait. Such people are usually healthy, although a fraction suffer some symptoms of sickle cell disease when there is an extended reduction of blood oxygen. Sickle-cell disease or sickle-cell anaemia (or anemia) is a blood disorder characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in their restricted movement through blood vessels, depriving downstream tissues of oxygen. The disease is chronic and lifelong: individuals are most often well, but their lives are punctuated by periodic painful attacks and a risk of various other complications. Life expectancy is shortened, with older studies reporting an average life expectancy of 42 and 48 years for males and females, respectively. Sickle-cell disease occurs more commonly in people (or their descendants) from parts of sub-Saharan Africa, where malaria is or was common, but it also occurs in people of other ethnicities. This is because those with one or two alleles of the sickle-cell disease are resistant to malaria since the sickle red blood cells are not conducive to the parasites - in areas where malaria is common, there is a survival value in carrying the sickle-cell genes. This collection of clinical findings was unknown until the explanation of the sickle cells in 1904 by the Chicago cardiologist and professor of medicine James B. Herrick (1861-1954) whose intern Ernest Edward Irons (1877-1959) found "peculiar elongated and sickle shaped" cells in the blood of Walter Clement Noel, a 20 year old first year dental student from Grenada after Noel was admitted to the Chicago Presbyterian Hospital in December 1904 suffering from anaemia. Noel was readmitted several times over the next three years for "muscular rheumatism" and "bilious attacks". Noel completed his studies and returned to the capital of Grenada (St. George's) to practice dentistry. He died of pneumonia in 1916 and is buried in the Catholic cemetery at Sauteurs in the north of Grenada. The disease was named "sickle-cell anaemia" by Vernon Mason in 1922. In retrospect some elements of the disease had been recognized earlier: a paper in the Southern Journal of Medical Pharmacology in 1846 described the absence of a spleen in the autopsy of a runaway slave. The African medical literature reported this condition in the 1870s where it was known locally as ogbanjes ("children who come and go") because of the very high infant mortality rate caused by this condition. A history of the condition tracked reports back to 1670 in one Ghanaian family. Also, the practice of using tar soap to cover blemishes caused by sickle-cell sores was prevalent in the African American community.[citation needed] Linus Pauling and colleagues were the first, in 1949, to demonstrate that sickle cell disease occurs as a result of an abnormality in the haemoglobin molecule. This was the first time a genetic disease was linked to a mutation of a specific protein, a milestone in the history of molecular biology. The origin of the mutation that led to the sickle-cell gene was initially thought to be in the Arabian peninsula, spreading to Asia and Africa. It is now known, from evaluation of chromosome structures, that there have been at least four independent mutational events, three in Africa and a fourth in either Saudi Arabia or central India. These independent events occurred between 3,000 and 6,000 generations ago, approximately 70-150,000 years.