Department of General Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, NO. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
Clin Rheumatol. 2021 Oct;40(10):4325-4339. doi: 10.1007/s10067-021-05587-w. Epub 2021 Feb 26.
Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease caused by ADA2 gene mutation that is characterized by three phenotype domains: vasculopathy and inflammation, hematological abnormality, and immunodeficiency. Most patients are pediatric patients; adult-onset patients are only occasionally reported. To describe a Chinese case of adult-onset DADA2 in a Chinese patient and explore the genotype and phenotype characteristics of adult-onset DADA2. We examined the clinical, serological, and genetic features of a Chinese adult-onset DADA2 patient. English literature on DADA2 was reviewed. The clinical and genetic characteristics of different age and mutation subgroups were compared. A Chinese Han male presented with recurrent fever, rash, immunodeficiency, and significant vascular events since the age of 25 years. Serum ADA2 activity was diminished, and genotyping revealed a unique compound heterozygous mutation of exon2-10del/exon7del in the ADA2 gene leading to complete exon 7 deletion. Treatment with a TNFα inhibitor achieved disease control. A total of 269 cases carrying 102 mutations were analyzed through a literature review. Adult-onset patients had few symptoms in all three clinical domains; vasculopathy and inflammation were the major symptoms. Patients with null mutations had early disease onset and more frequent hematological abnormalities and immunodeficiency. Patients in all subgroups responded well to TNFα inhibitors. We reported the first Chinese adult-onset DADA2 patient, with a unique mutation. Screening for and differentiation of DADA2 are recommended for patients of all ages, as they might become symptomatic later in life and treatment strategies differ from those of traditional vasculitis. Key Points • We report a novel compound heterozygous deletion mutations of exons 2-10 and exon 7, leading to complete loss of exon 7 in the ADA2 gene. • Adult-onset DADA2 patients had high similarity to systemic vasculitis. • Null mutations contribute to earlier disease onset and more aggressive disease. • We suggest screening for DADA2 in patients with significant central vasculitis, hematological abnormality and immunodeficiency.
腺苷脱氨酶 2 缺乏症（DADA2）是一种常染色体隐性疾病，由 ADA2 基因突变引起，其特征为三个表型域：血管病变和炎症、血液学异常和免疫缺陷。大多数患者为儿科患者；仅偶尔报告成人发病。描述一位中国成人发病的 DADA2 患者，并探讨成人发病的 DADA2 的基因型和表型特征。我们检查了一位中国成人发病的 DADA2 患者的临床、血清学和遗传特征。回顾了 DADA2 的英文文献。比较了不同年龄和突变亚组的临床和遗传特征。一位中国汉族男性，25 岁起出现反复发热、皮疹、免疫缺陷和严重血管事件。血清 ADA2 活性降低，基因分型显示 ADA2 基因外显子 2-10del/exon7del 复合杂合突变导致外显子 7 完全缺失。使用 TNFα 抑制剂治疗达到疾病控制。通过文献回顾分析了携带 102 种突变的 269 例患者。成人发病患者在所有三个临床领域的症状均较少；血管病变和炎症是主要症状。无功能突变患者疾病发病较早，更常出现血液学异常和免疫缺陷。所有亚组患者均对 TNFα 抑制剂反应良好。我们报告了首例中国成人发病的 DADA2 患者，存在独特的突变。建议对所有年龄段的患者进行 DADA2 的筛查和鉴别诊断，因为他们可能在以后的生活中出现症状，治疗策略与传统血管炎不同。关键点 • 我们报告了 ADA2 基因外显子 2-10 和外显子 7 的新型复合杂合缺失突变，导致外显子 7 完全缺失。 • 成人发病的 DADA2 患者与系统性血管炎高度相似。 • 无功能突变导致疾病发病较早，病情更具侵袭性。 • 我们建议对有明显中枢血管炎、血液学异常和免疫缺陷的患者进行 DADA2 筛查。
