Department of Clinical Immunology and Rheumatology, St. John's National Academy of Health Sciences, Bangalore, India.
Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Clin Rheumatol. 2021 Oct;40(10):3883-3896. doi: 10.1007/s10067-021-05711-w. Epub 2021 Mar 31.
Deficiency of adenosine deaminase 2 (DADA2) is a monogenic disease caused by biallelic mutations in ADA2 gene (previously CECR1). The aim of this review was to describe the clinical phenotypes, genetics, pathogenesis and treatment of DADA2. ADA2 is highly expressed on myeloid cells and deficiency leads to polarisation of macrophages to an M1 inflammatory type and activation of neutrophils. The pathogenesis of immunological and haematological manifestations is less clear. The spectrum of clinical presentations varies widely from asymptomatic individual to severe vasculitis, several autoinflammatory, immunological and haematological manifestations. Initially considered a childhood disease, the first presentation is now being reported well into adulthood. Vasculitis closely resembles polyarteritis nodosa. Livedoid reticularis/racemosa like skin rash and central nervous system involvement in the form of ischemic or haemorrhagic stroke are dominant manifestations. Immunological manifestations include hypogammaglobulinemia and recurrent infections. Lymphopenia is the most common haematological manifestation; pure red cell aplasia and bone marrow failure has been reported in severe cases. The disease is extremely heterogeneous with variable severity noted in patients with the same mutation and even within family members. Tumour necrosis factor inhibitors are currently the treatment of choice for vasculitic and inflammatory manifestations and also prevent strokes. Haematopoietic stem cell transplantation is a curative option for severe haematological manifestations like pure red cell aplasia, bone marrow failure and immunodeficiency. Further research is required to understand pathogenesis and all clinical aspects of this disease to enable early diagnosis and prompt treatment. Key Points • Deficiency of adenosine deaminase 2 (DADA2) is a monogenic disease caused by biallelic mutations in ADA2 gene. • The clinical features include vasculitis resembling polyarteritis nodosa, autoinflammation, haematological manifestations and immunodeficiency. • The severity varies widely from mild to fatal even in patients within a family and with the same mutation. • The treatment of choice for inflammatory and vasculitic disease is tumour necrosis factor α blockers. Bone marrow transplant may be considered for severe haematological disease.
腺苷脱氨酶 2 缺乏症（DADA2）是一种由 ADA2 基因（先前称为 CECR1）双等位基因突变引起的单基因疾病。本综述旨在描述 DADA2 的临床表型、遗传学、发病机制和治疗方法。ADA2 在髓样细胞上高度表达，其缺乏导致巨噬细胞向 M1 炎症型极化，并激活中性粒细胞。免疫和血液系统表现的发病机制尚不清楚。临床表现谱差异很大，从无症状个体到严重血管炎、多种自身炎症、免疫和血液系统表现。最初被认为是一种儿童疾病，现在首次报告的发病年龄已进入成年期。血管炎与结节性多动脉炎非常相似。网状皮肤疹样网状皮肤疹和以缺血性或出血性中风为形式的中枢神经系统受累是主要表现。免疫表现包括低丙种球蛋白血症和反复感染。淋巴细胞减少是最常见的血液系统表现；在严重病例中已报道纯红细胞再生障碍和骨髓衰竭。该疾病具有极高的异质性，在具有相同突变的患者中甚至在家庭成员中观察到疾病严重程度不同。肿瘤坏死因子抑制剂目前是血管炎和炎症表现的治疗选择，也可预防中风。造血干细胞移植是治疗纯红细胞再生障碍、骨髓衰竭和免疫缺陷等严重血液系统表现的一种根治方法。需要进一步研究以了解该疾病的发病机制和所有临床方面，从而实现早期诊断和及时治疗。 关键点 • 腺苷脱氨酶 2 缺乏症（DADA2）是一种由 ADA2 基因双等位基因突变引起的单基因疾病。 • 临床表现包括类似于结节性多动脉炎的血管炎、自身炎症、血液系统表现和免疫缺陷。 • 即使在家族内和具有相同突变的患者中，严重程度差异也很大。 • 肿瘤坏死因子 α 阻滞剂是治疗炎症和血管炎疾病的首选方法。对于严重的血液系统疾病，可能需要考虑骨髓移植。
