背景:腺苷脱氨酶2(DADA2)缺乏是由ADA2基因突变引起的常染色体隐性自身炎性疾病。DADA2具有广泛的临床表现。除了系统性表现,我们可以将DADA2的大部分体征和症状分为三组血管炎,血液学异常,和免疫失调。最主要的血管炎特征是皮肤表现,主要是以花叶草/网状的形式,和早发性缺血性或出血性中风。在许多DADA2病例中发现的低丙种球蛋白血症将免疫缺陷带入鉴别诊断。细胞减少症,纯红细胞再生障碍(PRCA),骨髓衰竭(BMF)是DADA中常见的血液学异常。
方法:我们介绍11例诊断为DADA2的患者,包括两个兄弟姐妹,一组双胞胎姐妹,还有一个父亲和他的女儿和儿子。10名患者(91%)有近亲父母。所有患者均表现为总状/网状。10例患者(91%)报告发热发作,7人(64%)曾经历过中风。只有一名患者患有高血压。其中两名患者(11%)的免疫球蛋白水平降低。其中一名患者出现PRCA。除了有G321E突变的PRCA患者,我们所有的病人都有G47R突变,DADA2患者中最常见的突变。除了一名患者不幸在诊断和开始适当治疗之前去世,其他患者的症状目前得到控制;其中两名患者症状轻微,目前正在接受秋水仙碱治疗,其他八个人对反TNFs反应良好。PRCA患者仍患有血液学异常,是骨髓移植的候选人。
结论:考虑到其表现和鉴别诊断,DADA2不仅仅是一种风湿病,把这种疾病介绍给血液学家,神经学家,和免疫学家必须开始迅速和适当的治疗。抗TNFs在解决DADA2患者症状方面的功效已得到证实,但不适用于有血液学表现的患者。同样,它们有效地控制了我们队列患者的症状,除了一名血细胞减少症患者。
BACKGROUND: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease caused by mutations in the ADA2 gene. DADA2 has a broad spectrum of clinical presentations. Apart from systemic manifestations, we can categorize most of the signs and symptoms of DADA2 into the three groups of vasculitis, hematologic abnormalities, and immunologic dysregulations. The most dominant vasculitis features are skin manifestations, mostly in the form of livedo racemosa/reticularis, and early onset ischemic or hemorrhagic strokes. Hypogammaglobulinemia that is found in many cases of DADA2 brings immunodeficiencies into the differential diagnosis. Cytopenia, pure red cell aplasia (PRCA), and bone marrow failure (BMF) are the hematologic abnormalities commonly found in DADA.
METHODS: We introduce eleven patients with DADA2 diagnosis, including two brothers and sisters, one set of twin sisters, and one father and his daughter and son. Ten patients (91%) had consanguineous parents. All the patients manifested livedo racemose/reticularis. Ten patients (91%) reported febrile episodes, and seven (64%) had experienced strokes. Only one patient had hypertension. Two of the patients (11%) presented decreased immunoglobulin levels. One of the patients presented with PRCA. Except for the PRCA patient with G321E mutation, all of our patients delivered G47R mutation, the most common mutation in DADA2 patients. Except for one patient who unfortunately passed away before the diagnosis was made and proper treatment was initiated, the other patients\' symptoms are currently controlled; two of the patients presented with mild symptoms and are now being treated with colchicine, and the eight others responded well to anti-TNFs. The PRCA patient still suffers from hematologic abnormalities and is a candidate for a bone marrow transplant.
CONCLUSIONS: Considering the manifestations and the differential diagnoses, DADA2 is not merely a rheumatologic disease, and introducing this disease to hematologists, neurologists, and immunologists is mandatory to initiate prompt and proper treatment. The efficacy of anti-TNFs in resolving the symptoms of DADA2 patients have been proven, but not for those with hematologic manifestations. Similarly, they were effective in controlling the symptoms of our cohort of patients, except for the one patient with cytopenia.