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Abstract：
Inherited defects in adenosine deaminase (ADA) cause a subtype of severe combined immunodeficiency (SCID) known as severe combined immune deficiency caused by adenosine deaminase defects (ADA-SCID). Most affected infants can receive a diagnosis while still asymptomatic by using an SCID newborn screening test, allowing early initiation of therapy. We review the evidence currently available and propose a consensus management strategy. In addition to treatment of the immune deficiency seen in patients with ADA-SCID, patients should be followed for specific noninfectious respiratory, neurological, and biochemical complications associated with ADA deficiency. All patients should initially receive enzyme replacement therapy (ERT), followed by definitive treatment with either of 2 equal first-line options. If an HLA-matched sibling donor or HLA-matched family donor is available, allogeneic hematopoietic stem cell transplantation (HSCT) should be pursued. The excellent safety and efficacy observed in more than 100 patients with ADA-SCID who received gammaretrovirus- or lentivirus-mediated autologous hematopoietic stem cell gene therapy (HSC-GT) since 2000 now positions HSC-GT as an equal alternative. If HLA-matched sibling donor/HLA-matched family donor HSCT or HSC-GT are not available or have failed, ERT can be continued or reinstituted, and HSCT with alternative donors should be considered. The outcomes of novel HSCT, ERT, and HSC-GT strategies should be evaluated prospectively in \"real-life\" conditions to further inform these management guidelines.
摘要：
腺苷脱氨酶（ADA）的遗传性缺陷会导致严重的联合免疫缺陷（SCID）亚型，称为由腺苷脱氨酶缺陷（ADA-SCID）引起的严重联合免疫缺陷。大多数受影响的婴儿可以通过使用SCID新生儿筛查测试在无症状的情况下接受诊断，允许早期开始治疗。我们回顾了目前可用的证据，并提出了共识管理策略。除了治疗ADA-SCID患者的免疫缺陷外，患者应随访特定的非感染性呼吸道，神经学,和与ADA缺乏相关的生化并发症。所有患者最初应接受酶替代疗法（ERT），其次是决定性的治疗与2个平等的一线选择。如果有HLA匹配的同胞供体或HLA匹配的家族供体，应继续进行异基因造血干细胞移植（HSCT）。自2000年以来，在100多名接受γ-逆转录病毒或慢病毒介导的自体造血干细胞基因治疗（HSC-GT）的ADA-SCID患者中观察到了出色的安全性和有效性，现在将HSC-GT定位为平等的替代方案。如果HLA匹配的同胞供体/HLA匹配的家族供体HSCT或HSC-GT不可用或失败，ERT可以继续或恢复，和HSCT与替代捐助者应考虑。新型HSCT的结果，ERT,和HSC-GT策略应在“现实生活”条件下进行前瞻性评估，以进一步告知这些管理指南。
