Objective: To analyze the clinical characteristics of spondyloenchondrodysplasia with immune dysregulation (SPENCDI). Methods: The clinical manifestations, laboratory examinations, treatment and genetic analysis of a patient diagnosed with SPENCDI who was admitted to the Department of Pediatrics in Peking Union Medical College Hospital in October 2016 were analyzed. Then literature review was done after searching articles in PubMed and several Chinese databases with the key words "spondyloenchondrodysplasia with immune dysregulation" up to the date of November 2017. Results: A 12-year-old girl was admitted to local hospital for complaint of "recurrent fever over one month" in October 2016. She was diagnosed with type Ⅱ autoimmune hepatitis for abnormal liver function, elevated immunoglobulin G, positive anti-liver-kidney microsomal antibody and medium to severe interface hepatitis verified by liver biopsy. Systemic lupus erythematosus was also suspected based on positive antinuclear antibody and anti-dsDNA antibody, decreased complements, reduced white blood cells and hemoglobin. Methylprednisolone and azathioprine were started based on the diagnosis. However, she experienced mycoplasma pneumoniae and suspected fungal infections during the treatment. Detailed history revealed the history of developmental retardation since birth, and cerebral palsy diagnosed when she was 2 years old. She also underwent surgery at the age of eight for eversion of her right foot. Based on the abnormal findings of immune system, skeleton and nervous system, certain primary immunodeficiency disease was speculated. Gene sequencing was performed, which revealed compound heterozygous mutations in ACP5 gene (NM_001111035.2) (c.798dupC, p. S267Lfs*20, paternal; c.716G>A, p. G239D, maternal). With X-ray of the vertebrae showed multiple platyspondyly, the diagnosis was corrected as SPENCDI and type Ⅱ autoimmune hepatitis. Then she was treated with prednisone (60 mg/d) and mycophenolate mofetil (1.5 g/d). All symptoms resolved on 3-month follow-up, with normalized activity indexes of autoimmune hepatitis and systemic lupus erythematosus. A total of 25 articles (1 Chinese, 24 English) were reviewed, with 74 SPENCDI patients reported. The most common manifestations were skeletal abnormalities (74/74, 100%), autoimmune diseases (47/74, 63.5%), dwarfism (45/74, 60.8%), and nervous system symptoms (25/74, 33.8%). A few patients with simple spondyloenchondrodysplasia were treated with growth hormone, and those who with autoimmune diseases were treated with immunosuppressants, all of whom were improved to certain extent. Conclusions: Vertebral and metaphyseal dysplasia, nervous system symptoms, and strong predisposition to autoimmune diseases are the hallmarks of SPENCDI. SPENCDI should be considered in dwarf with or without autoimmune diseases or nervous system symptoms.
目的： 总结椎体软骨发育不良伴免疫调节异常（SPENCDI）的临床特点。 方法： 报道2016年10月北京协和医院儿科收治的1例SPENCDI患儿的临床表现、治疗、转归和基因测序结果，并分别以"椎体软骨发育不良伴免疫调节异常""spondyloenchondrodysplasia"为检索词，检索截至2017年11月中文数据库（中国知网、万方数据库）及PubMed数据库的文献进行复习。 结果： 患儿女，12岁，因"间断发热1个月余"就诊，常规检查发现肝功能异常、血白细胞和血红蛋白降低。完善相关检查后，以"肝功能异常、IgG升高、抗肝肾微粒体抗体阳性、肝活检提示中重度肝界面炎"及"抗核抗体阳性、抗双链DNA抗体阳性、补体降低、血白细胞和血红蛋白减低"被诊断为"Ⅱ型自身免疫性肝炎，系统性红斑狼疮不除外"，给予甲泼尼龙及硫唑嘌呤治疗后，出现新发的肺炎支原体肺炎及可疑真菌感染。患儿自幼生长发育落后，2岁被诊为"脑瘫"，6岁始能独立行走，8岁行右足外翻矫正手术。行相关基因二代测序及Sanger验证，结果提示抗酒石酸酸性磷酸酶5基因（ACP5，NM_001111035.2）复合杂合突变：c.798dupC，p.S267Lfs*20，杂合，父源；c.716G>A，p.G239D，杂合，母源。完善胸腰椎侧位X线显示椎体明显变扁。遂确诊为SPENCDI，予以泼尼松龙60 mg/d，吗替麦考酚酯1.5 g/d治疗。3个月后随访，患儿无不适主诉，自身免疫性肝炎以及系统性红斑狼疮的活动指标均正常。文献检索发现25篇同类病例报道，其中中文1篇，英文24篇，共有74例患者，其主要临床表现依次是骨骼发育异常（74/74，100%）、自身免疫性疾病（47/74，63.5%）、矮小（45/74，60.8%）、神经系统症状（25/74，33.8%）。少数单纯骨骼发育异常的患者给予生长激素治疗，合并自身免疫病的患者给予了相应的免疫抑制剂治疗，病情均获得一定程度的改善。 结论： 椎体及干骺端软骨发育异常、神经系统症状、自身免疫性疾病易感是SPENCDI的主要临床表现。对于单纯矮小或是合并自身免疫性疾病和（或）神经系统症状时，应警惕该病的存在。.
Keywords: Autoimmune diseases; Bone development; Genes; Immunologic deficiency syndromes.