Dianzani I, Garelli E, Ramenghi U
Department of Medical Sciences, University of Eastern Piedmont, Novara, Italy.
Paediatr Drugs. 2000 Sep-Oct;2(5):345-55. doi: 10.2165/00128072-200002050-00002.
Diamond Blackfan Anaemia (DBA) is a congenital disease characterised by defective erythroid progenitor maturation. It is usually diagnosed during the first year of life. The main clinical sign is profound isolated normochromic or macrocytic anaemia, with normal numbers and function of the other haemopoietic cells. Reticulocyte counts in patients with DBA are very low. Bone marrow reflects the defective erythropoiesis, showing a very low number of erythropoietic precursors and a reduction of erythroid burst-forming unit progenitor cells. The proliferation and differentiation of the other lineages are normal. More than one-third of patients have malformations, most often involving the upper limbs and head, and the urogenital or cardiovascular systems. However, the link between these malformations and defective erythropoiesis is unclear and a defect in a molecule acting on both early embryonic development and haematopoiesis has been proposed. Whereas most cases are sporadic, inheritance is observed in 10% of patients, with a dominant or, more rarely, recessive pattern. One locus on chromosome 19q13.2 encoding ribosomal protein S19 accounts for a quarter of patients with either the dominant or the sporadic form. Families not linked with this locus have also been described. The diagnosis of DBA may be difficult and differential diagnoses include Fanconi's anaemia and acquired erythroid aplasias. Erythrocyte adenosine deaminase levels are generally high in DBA patients, which may help in the diagnosis, but they are not pathognomic. Corticosteroids are the main treatment option in DBA and these agents induce erythropoiesis in over 60% of patients. Some patients achieve complete remission, which may be either corticosteroid-induced or spontaneous. The increased in vitro erythropoiesis occasionally induced by the addition of specific cytokines, namely interleukin (IL)-3 and stem cell factor (SCF), has suggested their use in vivo. However, few patients have responded to IL-3, whereas SCF administration, though interesting in theory, has not yet been attempted. Patients who do not respond to corticosteroids and those who have to discontinue treatment because of adverse events must rely on long term transfusions, and are thus exposed to all of the associated complications. Bone marrow or cord blood transplantation has been performed in some patients. The former approach is burdened with severe complications and high mortality.
先天性纯红细胞再生障碍性贫血（DBA）是一种先天性疾病，其特征为红系祖细胞成熟缺陷。通常在出生后第一年内被诊断出来。主要临床体征为严重的单纯性正色素性或大细胞性贫血，其他造血细胞数量和功能正常。DBA患者的网织红细胞计数非常低。骨髓反映了红细胞生成缺陷，显示红细胞生成前体细胞数量非常低，红系爆式形成单位祖细胞减少。其他谱系的增殖和分化正常。超过三分之一的患者有畸形，最常见的是上肢和头部以及泌尿生殖系统或心血管系统受累。然而，这些畸形与红细胞生成缺陷之间的联系尚不清楚，有人提出存在一种作用于早期胚胎发育和造血的分子缺陷。虽然大多数病例是散发性的，但10%的患者有遗传现象，呈显性或更罕见的隐性模式。位于19号染色体q13.2上的一个编码核糖体蛋白S19的位点，占显性或散发性形式患者的四分之一。也有与该位点无关的家系报道。DBA的诊断可能困难，鉴别诊断包括范可尼贫血和获得性纯红细胞再生障碍。DBA患者的红细胞腺苷脱氨酶水平通常较高，这可能有助于诊断，但并非特异性的。皮质类固醇是DBA的主要治疗选择，这些药物可使60%以上的患者诱导红细胞生成。一些患者实现完全缓解，这可能是皮质类固醇诱导的或自发的。添加特定细胞因子，即白细胞介素（IL）-3和干细胞因子（SCF）偶尔会在体外诱导红细胞生成增加，这提示了它们在体内的应用。然而，很少有患者对IL-3有反应，而SCF给药虽然理论上很有意义，但尚未尝试过。对皮质类固醇无反应的患者以及因不良事件而必须停止治疗的患者必须依赖长期输血，因此会面临所有相关并发症。一些患者已接受骨髓或脐血移植。前一种方法有严重并发症和高死亡率的负担。
