Thalassemia(地中海贫血)(also spelled thalassaemia) is an inherited autosomal recessive blood disease. In thalassemia the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin. This can cause the formation of abnormal hemoglobin molecules, thus causing anemia, the characteristic presenting symptom of the thalassemias.
Thalassemia(地中海贫血)is a quantitative problem of too few globins synthesized, whereas sickle-cell anemia (a hemoglobinopathy) is a qualitative problem of synthesis of an incorrectly functioning globin. Thalassemias usually result in underproduction of normal globin proteins, often through mutations in regulatory genes. Hemoglobinopathies imply structural abnormalities in the globin proteins themselves.[1] The two conditions may overlap, however, since some conditions which cause abnormalities in globin proteins (hemoglobinopathy) also affect their production (thalassemia). Thus, some thalassemias are hemoglobinopathies, but most are not. Either or both of these conditions may cause anemia.
The two major forms of the disease, alpha- and beta- (see below), are prevalent in discrete geographical clusters around the world - probably associated with malarial endemicity in ancient times. Alpha is prevalent in peoples of Western African descent, and is nowadays found in populations living in Africa and in the Americas. Beta is particularly prevalent among Mediterranean peoples, and this geographical association was responsible for its naming: Thalassa (θάλασσα) is Greek for the sea, Haema (αἷμα) is Greek for blood. In Europe, the highest concentrations of the disease are found in Greece, coastal regions in Turkey, in particular, Aegean Region such as Izmir, Balikesir, Aydin, Mugla and Mediterranean Region such as Antalya, Adana, Mersin, in parts of Italy, in particular, Southern Italy and the lower Po valley. The major Mediterranean islands (except the Balearics) such as Sicily, Sardinia, Malta, Corsica, Cyprus and Crete are heavily affected in particular. Other Mediterranean people, as well as those in the vicinity of the Mediterranean, also have high rates of thalassemia, including people from the West Asia and North Africa. Far from the Mediterranean, South Asians are also affected, with the world's highest concentration of carriers (16% of the population) being in the Maldives.
The thalassemia trait may confer a degree of protection against malaria, which is or was prevalent in the regions where the trait is common, thus conferring a selective survival advantage on carriers, and perpetuating the mutation. In that respect the various thalassemias resemble another genetic disorder affecting hemoglobin, sickle-cell disease.[2]
什么是地中海貧血？
地中海貧血
又称海洋性贫血，是一種先天的血液疾病，和父母的遺傳有關。1925年意大利首次报道了此病，目前该病已在全世界范围散布[1]。 患者的紅血球較脆弱且容易死亡，其帶氧能力亦不足，超過某種程度無法正常生活；在結婚以前健康檢查可以篩選出來，是一種隱性基因遺傳，患者红血球的体积较正常细胞小，且有时因血红素含量低较苍白或呈靶型（target cells)。
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病因
地中海贫血症的异常血红蛋白是在1904年由一个芝加哥医生發現的，直到1949年人们才通过电泳的方法發現异常血红蛋白比正常血红蛋白每个分子多了两到四个正电荷。氨基酸序列分析证明，地中海贫血症患者的血红蛋白的一个β亚基第6位氨基酸由正常的谷氨酸突变为异常的纈氨酸，导致血红蛋白的载氧能力下降。但是另一方面，患有地中海贫血症的患者对疟疾的抵抗能力要较正常人强，患上疟疾的地中海贫血症患者，平均存活率显著高于正常人群，因此在一些疟疾比较严重的地区，如赤道以南非洲，地中海贫血症患者的平均预期寿命反而高于正常人群。類型 根據血红蛋白中不同位置的損害可分成兩類：α地中海貧血與β地中海貧血。α地中海貧血是血紅蛋白中的α血紅蛋白鏈有缺損，β地中海貧血則是血紅蛋白中的β血紅蛋白鏈有缺損。鐮刀型紅血球疾病，又名鐮刀型貧血(Sickle Cell Anemia)和地中海貧血不同的是它只發生β血紅蛋白的缺陷。 α地中海貧血 α地中海貧血的患者會在HBA1、HBA2這兩個基因發生異常。在成人造成β蛋白鏈過度製造，在新生兒則是γ蛋白鏈過多。過多的β蛋白鏈形成四聚物(tetramers)使紅血球的攜氧能力降低。 β地中海貧血 β地中海貧血的患者則是在第11號染色體上的HBB基因發生突變。不正常的細胞會製造過量的α蛋白鏈，然後結合在紅血球的細胞膜上造成細胞膜損壞；若其濃度過高，則有形成有毒聚集體(aggregates)的可能。 症状 地中海貧血症有隱性、輕度和重度之分。重度患者通常不能存活；而兩個隱性或輕度患者結婚，他們的下一代則有1/4機會患有重度地中海貧血症。相反地，兩者中只有一位是存有地中海貧血症基因的話，不論程度如何，則下一代沒有此問題或只帶有隱性。 由於地中海型貧血的患者缺少正常的血紅素，紅血球攜氧功能差，體內主要造血器官骨髓與次要造血器官肝臟、脾臟均會進行旺盛的造血作用，但造出的紅血球也多半品質不佳，容易被破壞，成為惡性循環。骨髓增生會侵犯周圍的皮質骨，使骨骼較脆弱。旺盛的造血作用會消耗極多的養分與能量，使身體其他部位的養分供需失調。不斷的輸血可以改善貧血的症狀，也可避免過度的造血作用，但血紅素中的鐵質會過度存在身體中，並堆積至各重要器官造成器官病變。 而生活中，地中海貧血患者因血紅素帶氧量不足而影響患者在體力上的差異，患者不適宜進行太激烈的運動。另外亦因為血紅素不足的關係，患者比較容易有頭暈、頭痛甚至腰痛的症狀，B型的可能會死亡，只能活到10幾歲的可能。 診斷 實驗室檢查：外周血象呈小細胞低色素性貧血，紅細胞大小不等，中央淺染區擴大，出現異形、靶形、碎片紅細胞和有核紅細胞、點彩紅細胞、嗜多染性紅細胞、豪‧周氏小體等；網織紅細胞正常或增高。骨髓象呈紅細胞系統增生明顯活躍，以中、晚幼紅細胞佔多數，成熟紅細胞改變與外周血相同。紅細胞滲透脆性明顯減低。HbF含量明顯增高，大多＞0.40，這是診斷重型β地貧的重要依據。顱骨X線片可見顱骨內外板變薄、板障增寬，在骨皮質間出現垂直短髮樣骨刺。 治療 需进行骨髓移植。 |
