Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Istanbul, Turkey.
Curr Opin Rheumatol. 2020 Jan;32(1):3-14. doi: 10.1097/BOR.0000000000000669.
To recap the expanding clinical spectrum, genotype-phenotype associations and treatment options in the light of recently published articles regarding the deficiency of adenosine deaminase 2 (DADA2).
Whole-exome sequencing enabled novel clinical phenotypes associated with ADA2 mutations. Since its discovery, the phenotypic spectrum of DADA2 has substantially expanded to cover Diamond-Blackfan anaemia, cytopenia and immunodeficiency syndromes. In addition to elevated TNF alpha levels, increased levels of interferon-stimulated genes were also detected in patients with DADA2. Given the absence of clinical trials until now, no standard treatment strategy exists for DADA2. Currently, anti-TNF alpha agents are the mainstay of treatment, based on the data both from the initial two reports and from subsequent studies. However, it is still unclear how to manage asymptomatic patients with ADA2 mutation and/or with absent ADA2 activity and what is the optimal duration of anti-TNF therapy.
Among a total of 206 DADA2 patients described so far, the overall mortality was found as 8.3%. Biallelic homozygous G47R mutations were mostly associated with a vascular phenotype, whereas patients with homozygous R169Q mutations seem to display a mixed clinical phenotype including vascular, haematological and immunological manifestations. HSCT should be reserved as a curative treatment option for DADA2 patients unresponsive to the anti-TNF therapy, as it carries a significant morbidity.
根据最近发表的关于腺苷脱氨酶 2 （DADA2）缺乏的文章，回顾不断扩大的临床谱、基因型-表型相关性和治疗选择。
全外显子组测序使与 ADA2 突变相关的新的临床表型成为可能。自发现以来，DADA2 的表型谱已大大扩展，涵盖 Diamond-Blackfan 贫血、细胞减少和免疫缺陷综合征。除了 TNF-α 水平升高外，还在 DADA2 患者中检测到干扰素刺激基因水平升高。由于迄今为止缺乏临床试验，因此目前尚无针对 DADA2 的标准治疗策略。目前，基于最初两项报告和随后研究的数据，抗 TNF-α 药物是治疗的主要方法。然而，对于无症状的 ADA2 突变患者和/或无 ADA2 活性的患者，如何进行管理，以及抗 TNF 治疗的最佳持续时间仍不清楚。
在迄今为止描述的总共 206 例 DADA2 患者中，总死亡率为 8.3%。双等位基因纯合 G47R 突变主要与血管表型相关，而纯合 R169Q 突变患者似乎表现出混合的临床表型，包括血管、血液和免疫表现。对于对 TNF 治疗无反应的 DADA2 患者，HSCT 应作为一种有治愈潜力的治疗选择，因为它具有显著的发病率。
