de Silva S, Fisher C A, Premawardhena A, Lamabadusuriya S P, Peto T E, Perera G, Old J M, Clegg J B, Olivieri N F, Weatherall D J
Thalassaemia Unit, General Hospital, Kurunegala, Sri Lanka.
Lancet. 2000 Mar 4;355(9206):786-91. doi: 10.1016/s0140-6736(99)08246-x.
Thalassaemias pose an increasing problem for the Indian subcontinent and many Asian countries. We analysed the different types of thalassaemia in the Sri Lankan population, surveyed gene frequencies in schoolchildren, and estimated the burden of disease and requirements for its control.
We analysed blood samples from patients attending clinics in nine hospitals and defined the different types of beta thalassaemia by high-performance liquid chromatography (HPLC) and DNA analysis. The range of mutations was obtained by analysis of beta-globin genes. Capillary blood was obtained from schoolchildren from different parts of the island and analysed by HPLC to provide an approximate assessment of the carrier frequency of beta thalassaemia and haemoglobin E (HbE). To estimate the frequency of alpha thalassaemia the alpha-globin genotypes were also analysed when it was possible.
Blood samples were obtained from 703 patients with beta thalassaemia and from 1600 schoolchildren. The thalassaemia mutations were unevenly spread. Although 23 different beta-thalassaemia mutations were found, three accounted for the thalassaemia phenotype in about 70% of the patients, most whom are homozygotes or compound heterozygotes for IVS1-5 (G-->C) or IVS1-1 (G-->A). The third common mutation, codon 26 (G-->A), which produces HbE, interacts with one or other of these mutations to produce HbE/beta thalassaemia; this comprises 13.0-30.9% of cases in the main centres. Samples from 472 patients were analysed to determine the alpha-globin genotype. Overall, 15.5% patients were carriers for deletion forms of alpha+ thalassaemia. Average gene frequencies showed that there will be more than 2000 patients requiring treatment at any one time, in the future, of whom those with HbE/beta thalassaemia will account for about 40%.
In Sri Lanka, interactions of the two common beta-thalassaemia alleles will nearly always result in a transfusion-dependent disorder. However, about 40% of patients will have HbE/beta thalassaemia, which has a variable course. The management of these disorders could require about 5% of the total health budget. We need to learn more about the natural history and appropriate management of HbE/beta thalassaemia if resources are to be used effectively.
地中海贫血在印度次大陆和许多亚洲国家构成了日益严重的问题。我们分析了斯里兰卡人群中不同类型的地中海贫血，调查了学童中的基因频率，并估计了疾病负担及其控制需求。
我们分析了来自九家医院诊所患者的血样，并通过高效液相色谱法（HPLC）和DNA分析确定了不同类型的β地中海贫血。通过分析β珠蛋白基因获得突变范围。从该岛不同地区的学童中采集毛细血管血样，并通过HPLC进行分析，以大致评估β地中海贫血和血红蛋白E（HbE）的携带者频率。在可能的情况下，还分析α珠蛋白基因型以估计α地中海贫血的频率。
采集了703例β地中海贫血患者和1600名学童的血样。地中海贫血突变分布不均。虽然发现了23种不同的β地中海贫血突变，但其中三种突变导致约70%的患者出现地中海贫血表型，其中大多数是IVS1-5（G→C）或IVS1-1（G→A）的纯合子或复合杂合子。第三种常见突变，密码子26（G→A），产生HbE，与这些突变中的一种或另一种相互作用，产生HbE/β地中海贫血；在主要中心，这占病例的13.0-30.9%。分析了472例患者的样本以确定α珠蛋白基因型。总体而言，15.5%的患者是α+地中海贫血缺失型的携带者。平均基因频率表明，未来任何时候将有超过2000名患者需要治疗，其中HbE/β地中海贫血患者约占40%。
在斯里兰卡，两种常见的β地中海贫血等位基因的相互作用几乎总是会导致一种依赖输血的疾病。然而，约40%的患者将患有HbE/β地中海贫血，其病程各不相同。这些疾病的管理可能需要约占卫生总预算5%的资金。如果要有效利用资源，我们需要更多地了解HbE/β地中海贫血的自然史和适当管理方法。
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