Department of Microbiology, Immunology and Molecular Genetics, and the Division of Hematology & Oncology, Department of Pediatrics, David Geffen School of Medicine University of California, Los Angeles, Calif.
Department of Medicine and Biochemistry, Duke University Medical Center, Durham, NC.
J Allergy Clin Immunol. 2019 Mar;143(3):852-863. doi: 10.1016/j.jaci.2018.08.024. Epub 2018 Sep 5.
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.
腺苷脱氨酶（ADA）遗传缺陷导致一种严重联合免疫缺陷（SCID）亚型，称为由腺苷脱氨酶缺陷引起的严重联合免疫缺陷（ADA-SCID）。大多数受影响的婴儿在无症状时可以通过 SCID 新生儿筛查测试进行诊断，从而可以早期开始治疗。我们回顾了目前可用的证据，并提出了一项共识管理策略。除了治疗 ADA-SCID 患者的免疫缺陷外，还应针对与 ADA 缺乏相关的特定非传染性呼吸、神经和生化并发症对患者进行随访。所有患者最初都应接受酶替代疗法（ERT），然后根据两种同等一线选择中的任何一种进行确定性治疗。如果有 HLA 匹配的同胞供体或 HLA 匹配的家族供体，应进行同种异体造血干细胞移植（HSCT）。自 2000 年以来，接受过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 100 多名 ADA-SCID 患者观察到了极好的安全性和疗效，现在将 HSC-GT 定位为同等的替代方案。如果 HLA 匹配的同胞供体/HLA 匹配的家族供体 HSCT 或 HSC-GT 不可用或已失败，可以继续或重新开始 ERT，并且可以考虑使用替代供体进行 HSCT。新型 HSCT、ERT 和 HSC-GT 策略的结果应在“真实生活”条件下进行前瞻性评估，以进一步为这些管理指南提供信息。
