Abstract

Objective

To describe the clinical features, genotype, and treatment approaches of patients with confirmed adenosine deaminase 2 (ADA2) deficiency with dissimilar phenotypes.

Methods

A case series of five DADA2 patients from three families was presented. The clinical and laboratory data, treatment protocols, and outcome of the patients were recorded from the patients’ medical charts. ADA2 gene was screened by next generation sequencing first and then verified by Sanger sequencing. Serum ADA2 enzyme activity was measured by modified spectrophotometric method.

Results

The median (min–max) age at onset of symptoms and age at diagnosis were 11 (9–13.8) years and 15 (9–19) years, respectively. The median (min–max) follow-up period was 8 (6–45) months. There was consanguinity in two families (2/3). The main clinical manifestations are musculoskeletal (5/5), dermatological (4/5), and neurological (2/5). Homozygosity for the p.G47R mutation in ADA2 gene was detected in three patients. A homozygous mutation in ADA2 gene (c.650 T > A; p.Val217Asp) was detected in two siblings. Plasma ADA2 enzymatic activity was absent in all patients. Anti-tumor necrosis factor (TNF) therapy was commenced, and all patients became clinically inactive with normal acute-phase reactants.

Conclusion

ADA2 mutations should be checked in patients with presence of inflammation and livedoid vasculitis when they have neurological findings, especially in the form of stroke; and a history suggesting for an inherited disease; or presence of resistance to conventional treatment. Besides, anti-TNF seems to be useful for treatment of DADA2.

中文翻译：

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ADA2缺乏症：5名具有不同表型的患者的病例系列。

摘要

目的

描述具有不同表型的确诊腺苷脱氨酶2（ADA2）缺乏症患者的临床特征，基因型和治疗方法。

方法

介绍了来自三个家庭的五例DADA2患者的病例系列。从患者的病历记录患者的临床和实验室数据，治疗方案和结果。首先通过下一代测序筛选ADA2基因，然后通过Sanger测序进行验证。用改进的分光光度法测定血清ADA2酶活性。

结果

症状发作的中位（最小-最大）年龄和诊断时的年龄分别为11（9-13.8）岁和15（9-19）岁。中位（最小-最大）随访期为8（6-45）个月。有两个家庭的血缘关系（2/3）。主要临床表现为肌肉骨骼（5/5），皮肤病学（4/5）和神经病学（2/5）。在三例患者中检测到ADA2基因p.G47R突变的纯合性。在两个同胞中检测到ADA2基因的纯合突变（c.650 T> A; p.Val217Asp）。所有患者均无血浆ADA2酶活性。开始了抗肿瘤坏死因子（TNF）治疗，所有患者在临床上都没有正常的急性期反应物。

结论

有神经系统疾病，特别是中风形式的炎症和活体血管炎患者，应检查ADA2突变；以及暗示遗传病的病史；或对常规治疗有抗药性。此外，抗TNF似乎可用于治疗DADA2。