Escherich Carolin, Bötticher Benedikt, Harmsen Stefani, Hömberg Marc, Schaper Jörg, Lorenz Myriam Ricarda, Schwarz Klaus, Borkhardt Arndt, Oommen Prasad Thomas
Department of Pediatric Oncology, Hematology and Clinical Immunology, University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Front Pediatr. 2022 Jun 14;10:885893. doi: 10.3389/fped.2022.885893. eCollection 2022.
Deficiency of Adenosine Deaminase Type 2 (DADA2) is a rare autosomal recessive inherited disorder with a variable phenotype including generalized or cerebral vasculitis and bone marrow failure. It is caused by variations in the adenosine deaminase 2 gene (), which leads to decreased adenosine deaminase 2 enzyme activity. Here we present three instructive scenarios that demonstrate DADA2 spectrum characteristics and provide a clear and thorough diagnostic and therapeutic workflow for effective patient care. Patient 1 illustrates cerebral vasculitis in DADA2. Genetic analysis reveals a compound heterozygosity including the novel variant, p.V325Tfs7. In patient 2, different vasculitis phenotypes of the DADA2 spectrum are presented, all resulting from the homozygous mutation p.Y453C. In this family, the potential risk for siblings is particularly evident. Patient 3 represents pure red cell aplasia with bone marrow failure in DADA2. Here, ultimately, stem cell transplantation is considered the curative treatment option. The diversity of the DADA2 spectrum often delays diagnosis and treatment of this vulnerable patient cohort. We therefore recommend early ADA2 enzyme activity measurement as a screening tool for patients and siblings at risk, and we expect early steroid-based remission induction will help avoid fatal outcomes.
2型腺苷脱氨酶缺乏症（DADA2）是一种罕见的常染色体隐性遗传性疾病，其表型多样，包括全身性或脑部血管炎以及骨髓衰竭。它由腺苷脱氨酶2基因（）的变异引起，导致腺苷脱氨酶2酶活性降低。在此，我们展示了三个具有指导意义的病例，以说明DADA2的谱系特征，并为有效的患者护理提供清晰、全面的诊断和治疗流程。病例1展示了DADA2中的脑部血管炎。基因分析显示为复合杂合子，包括新的变异体p.V325Tfs7。病例2呈现了DADA2谱系的不同血管炎表型，均由纯合的p.Y453C突变引起。在这个家族中，兄弟姐妹的潜在风险尤为明显。病例3代表了DADA2中伴有骨髓衰竭的纯红细胞再生障碍。在此，最终干细胞移植被视为治愈性治疗选择。DADA2谱系的多样性常常延误对这一脆弱患者群体的诊断和治疗。因此，我们建议将早期ADA2酶活性检测作为对有风险的患者及其兄弟姐妹的筛查工具，并且我们期望早期基于类固醇的缓解诱导将有助于避免致命后果。
