Abstract：
Inherited defects in the adenosine deaminase (ADA) gene typically cause severe combined immunodeficiency. In addition to infections, ADA-deficient patients can present with neurodevelopmental, behavioral, hearing, skeletal, lung, heart, skin, kidney, urogenital, and liver abnormalities. Some patients also suffer from autoimmunity and malignancies. In recent years, there have been remarkable advances in the management of ADA deficiency. Most ADA-deficient patients can be identified by newborn screening for severe combined immunodeficiency, which facilitates early diagnosis and treatment of asymptomatic infants. Most patients benefit from enzyme replacement therapy (ERT). Allogeneic hematopoietic cell transplantation from an HLA-matched sibling donor or HLA-matched family member donor with no conditioning is currently the preferable treatment. When matched sibling donor or matched family member donor is not available, autologous ADA gene therapy with nonmyeloablative conditioning and ERT withdrawal, which is reported in recent studies to result in 100% overall survival and 90% to 95% engraftment, should be pursued. If gene therapy is not immediately available, ERT can be continued for a few years, although its excessive cost might be prohibitive. The recent improved outcome of hematopoietic cell transplantation using HLA-mismatched family-related donors or HLA-matched unrelated donors, after reduced-intensity conditioning, suggests that such procedures might also be considered rather than continuing ERT for prolonged periods. Long-term follow-up will further assist in determining the optimal treatment approach for ADA-deficient patients.
摘要：
腺苷脱氨酶（ADA）基因的遗传缺陷通常会导致严重的联合免疫缺陷（SCID）。除了感染,ADA缺乏的患者可以表现为神经发育，行为，听力,骨骼，肺，心,皮肤,肾,泌尿生殖系统,和肝脏异常。一些患者还患有自身免疫和恶性肿瘤。近年来,ADA缺陷的管理取得了显著进展。大多数ADA缺陷患者可以通过新生儿SCID筛查来识别，这有利于无症状婴儿的早期诊断和治疗。大多数患者受益于酶替代疗法（ERT）。来自HLA匹配的同胞供体（MSD）或HLA匹配的家族成员供体（MFD）的同种异体造血细胞移植（HCT）没有调理是目前优选的治疗方法。当MSD或MFD不可用时，自体ADA基因治疗（GT）与非清髓性预处理和ERT戒断，据报道，最近的研究导致100％的总生存率和90-95％的植入，应该追求。如果GT不是立即可用，ERT可以持续几年，尽管它的过高成本可能令人望而却步。使用HLA不匹配的家族相关供体或HLA匹配的无关供体的HCT的近期改善结果，在降低强度调理后，建议也可以考虑这种程序，而不是长时间继续ERT。长期随访将进一步有助于确定ADA缺乏患者的最佳治疗方法。
