Department of Pediatric Rheumatology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
Department of Rheumatology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
Rheumatol Int. 2018 Jan;38(1):129-136. doi: 10.1007/s00296-017-3740-3. Epub 2017 May 17.
Deficiency of adenosine deaminase type 2 (DADA2) is a rare form of autoinflammatory disorder with limited reported cases. In this paper, we have presented the clinico-immunological, radiological and genetic characteristics of five surviving and three deceased childhood-onset DADA2 patients. We aimed to compare surviving and deceased patients in terms of clinical features and treatment modalities. Moreover, we have evaluated the causes of death in our DADA2 subjects together with the previously reported cases. Demographic features, clinical characteristics, imaging findings, mutations and pharmacological treatments of DADA2 subjects were noted from patient records of pediatric and adult rheumatology clinics in a retrospective and longitudinal nature. Eight patients from seven families were enrolled. While five of them were surviving, three of them had died due to various reasons. Median age of the patients at disease onset and diagnosis was 7 years (range 0.5-13 years) and 14 years (range 5-27 years), respectively. The main clinical manifestations were cutaneous findings (7/8), recurrent low-grade fever (6/8), neurological involvement (6/8) and gastrointestinal involvement (5/8). All patients had increased acute phase reactants at presentation and also during the disease flares. Until the diagnosis of DADA2 was confirmed, five patients have been followed-up with the diagnosis of PAN: two patients both with PAN and FMF, and one patient with CAPS and vasculitis. Demographic, clinical, neurological features and genetic mutations did not differ in surviving and deceased DADA2 patients. Deceased and surviving subjects differed in terms of treatment modalities after the diagnosis of DADA2. Anti-TNF alpha treatment has been initiated in five surviving patients as soon as the diagnosis of DADA2 was established. However, three patients who have died were not able to use sufficient doses of anti-TNF alpha treatment; in one case due to reluctance of patient and in two cases due to establishment of the definite diagnosis by genetic analysis at the same time with the last fatal DADA2 episode. Despite limited number of patients, this case series for the first time compares the phenotypic, genotypic and medication differences between surviving and deceased DADA2 patients. Anti-TNF alpha treatment seems to be efficient and lifesaving in DADA2 patients.
腺苷脱氨酶 2 型（DADA2）缺乏症是一种罕见的自身炎症性疾病，已有有限的报道病例。在本文中，我们介绍了五例存活和三例死亡的儿童发病 DADA2 患者的临床免疫、影像学和遗传学特征。我们旨在比较存活和死亡患者的临床特征和治疗方式。此外，我们评估了我们的 DADA2 患者的死亡原因，以及之前报道的病例。通过回顾性和纵向方式从儿科和成人风湿病诊所的患者记录中记录 DADA2 患者的人口统计学特征、临床特征、影像学发现、突变和药物治疗。从七个家庭中招募了 8 名患者。其中 5 名患者存活，3 名因各种原因死亡。患者发病和诊断时的中位年龄为 7 岁（范围 0.5-13 岁）和 14 岁（范围 5-27 岁）。主要临床表现为皮肤表现（7/8）、反复低度发热（6/8）、神经系统受累（6/8）和胃肠道受累（5/8）。所有患者在就诊时和疾病发作期间均有急性时相反应物升高。在确诊 DADA2 之前，5 例患者被诊断为 PAN：2 例患者同时患有 PAN 和 FMF，1 例患者同时患有 CAPS 和血管炎。存活和死亡的 DADA2 患者在人口统计学、临床、神经特征和基因突变方面无差异。在确诊 DADA2 后的治疗方式上，死亡和存活患者存在差异。一旦确诊 DADA2，5 例存活患者即开始接受抗 TNF-α治疗。然而，3 例死亡患者无法使用足够剂量的抗 TNF-α治疗；在一个病例中，由于患者的不情愿，在两个病例中，由于在最后一次致命的 DADA2 发作时同时进行基因分析确定了明确的诊断。尽管患者人数有限，但本病例系列首次比较了存活和死亡的 DADA2 患者之间的表型、基因型和药物治疗差异。抗 TNF-α治疗似乎对 DADA2 患者有效且能挽救生命。
