Angastiniotis Michael, Lobitz Stephan
Thalassemia International Federation, Strovolos 2083, Nicosia, Cyprus.
Department of Pediatric Oncology/Hematology, Kinderkrankenhaus Amsterdamer Straße, 50735 Cologne, Germany.
Int J Neonatal Screen. 2019 Mar 20;5(1):16. doi: 10.3390/ijns5010016. eCollection 2019 Mar.
Thalassemia syndromes are among the most serious and common genetic conditions. They are indigenous in a wide but specific geographical area. However, through migration they are spreading across regions not previously affected. Thalassemias are caused by mutations in the α () and β globin () genes and are usually inherited in an autosomal recessive manner. The corresponding proteins form the adult hemoglobin molecule (HbA) which is a heterotetramer of two α and two β globin chains. Thalassemia-causing mutations lead to an imbalanced globin chain production and consecutively to impaired erythropoiesis. The severity of the disease is largely determined by the degree of chain imbalance. In the worst case, survival is dependent on regular blood transfusions, which in turn cause transfusional iron overload and secondary multi-organ damage due to iron toxicity. A vigorous monitoring and treatment regime is required, even for the milder syndromes. Thalassemias are a major public health issue in many populations which many health authorities fail to address. Even though comprehensive care has resulted in long-term survival and good quality of life, poor access to essential components of management results in complications which increase the cost of treatment and lead to poor outcomes. These requirements are not recognized by measures such as the Global Burden of Disease project, which ranks thalassemia very low in terms of disability-adjusted life years (DALYs), and fails to consider that it ranks highly in the one to four-year-old age group, making it an important contributor to under-5 mortality. Thalassemia does not fulfil the criteria to be accepted as a target disease for neonatal screening. Nevertheless, depending on the screening methodology, severe cases of thalassemia will be detected in most neonatal screening programs for sickle cell disease. This is very valuable because: (1) it helps to prepare the affected families for having a sick child and (2) it is an important measure of secondary prevention.
地中海贫血综合征是最严重且常见的遗传性疾病之一。它们在广泛但特定的地理区域内流行。然而，通过移民，它们正在蔓延到以前未受影响的地区。地中海贫血是由α（）和β珠蛋白（）基因突变引起的，通常以常染色体隐性方式遗传。相应的蛋白质形成成人血红蛋白分子（HbA），它是由两条α珠蛋白链和两条β珠蛋白链组成的异源四聚体。导致地中海贫血的突变会导致珠蛋白链生成失衡，进而损害红细胞生成。疾病的严重程度在很大程度上取决于链失衡的程度。在最严重的情况下，生存依赖于定期输血，而输血又会导致输血性铁过载以及由于铁毒性引起的继发性多器官损害。即使对于较轻的综合征，也需要严格的监测和治疗方案。地中海贫血在许多人群中是一个重大的公共卫生问题，但许多卫生当局未能加以解决。尽管全面护理已带来长期生存和良好的生活质量，但由于难以获得管理的基本要素，导致出现并发症，增加了治疗成本并导致不良后果。诸如全球疾病负担项目等措施并未认识到这些需求，该项目在地中海贫血的残疾调整生命年（DALYs）方面将其排名极低，并且没有考虑到它在1至4岁年龄组中排名很高，使其成为5岁以下儿童死亡率的一个重要因素。地中海贫血不符合被接受为新生儿筛查目标疾病的标准。然而，根据筛查方法，在大多数镰状细胞病新生儿筛查项目中会检测到严重的地中海贫血病例。这非常有价值，因为：（1）它有助于让受影响的家庭为有患病儿童做好准备；（2）它是二级预防的一项重要措施。
