镰刀形红细胞贫血症_在线百科全书查询
镰刀形红细胞贫血症
定义
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。
主要症状
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。
病因
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。
英文资料
Sickle cell disease
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.[1]
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.
History
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.[14]
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.[15] 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.[16] These independent events occurred between 3,000 and 6,000 generations ago, approximately 70-150,000 years.
