摘要目的 总结以克罗恩病为主要临床表现的X连锁凋亡抑制因子(XIAP)缺陷病例的临床特点.方法 报道2016年5月浙江大学医学院附属儿童医院消化科收治的1例XIAP缺陷患儿的缶床表现、治疗、转归和基因测序结果,并以“克罗恩病”“XIAP”为检索词,检索2006年1月至2017年6月中文数据库及PUBMED数据库进行文献复习.结果 患儿男,6岁1月龄,因反复便血2个月余,加重伴发热腹痛2周入院.既往1年余前曾有“噬血细胞综合征、癫痫”病史.入院后完善相关检查,血常规提示轻度贫血(血红蛋白108 g/L);超敏C反应蛋白(86 rg/L)及红细胞沉降率(46 mm/lh)均升高;粪常规白或脓细胞及红细胞阳性;血生化提示低白蛋白血症(25.2 g/L),转氨酶(丙氨酸转氨酶175 U/L、天冬氨酸转氨酶229 U/L)升高,甘油三酯(4.41 mmol/L)升高,铁蛋白(＞1 650.0 μg/L)升高;小肠磁共振水成像:部分结肠、回肠肠壁增厚、强化.胶囊内镜:空肠黏膜多发小溃疡.肠镜提示结肠多发溃疡.肠镜病理:回肠末端及全结肠黏膜慢性活动性炎,部分伴小片坏死溃疡.骨髓细胞学检查可见少量吞噬细胞.诊断为“噬血细胞综合征、克罗恩病、败血症、癫痫、重度营养不良、低蛋白血症”,儿童克罗恩病活动指数(PCDAI)评分37.5分.基因检测发现XIAP基因存在半合子突变c.910G＞TchrX:123022501 p.G304X.父母均未检测出突变.该患儿经英夫利昔单抗治疗及巯嘌呤、糖皮质激素口服,病情缓解,PCDAI评分0分.文献检索共9篇,其中中文0篇,英文9篇,共有111例患者,炎症性肠病样表现约占33.3％,可相继或同时存在噬血细胞综合征、脾肿大等临床表现,单一治疗措施效果欠佳.结论 XIAP缺陷患儿表现多样,在临床表现复杂、对治疗不敏感的男性炎症性肠病患儿中行基因检测,对指导治疗及判断预后有重要意义.

abstractsObjective To analyze the clinical characteristics of X-linked inhibitor of apoptosis (XIAP) deficient patients with clinical manifestation of Crohn's disease.Methods Clinical manifestations,laboratory investigations,genetic testing and therapeutic interventions of one case of XIAP deficiency who was admitted to Department of Gastroenterology in Children's Hospital,Zhejiang University School of Medicine in May 2016 were summarized.PubMed and Chinese database for articles published from January 2016 to June 2017 were searched using the key words of ‘Crohn's disease'and ‘XIAP',and the relevant literature was reviewed.Results The case we reported was a 6-year-l-month-old boy with recurrent bloody stool for 2 months,and abdominal pain with fever for 2 weeks.The patient had a past history of hemophagocytic lymphohistiocytosis (HLH) and epilepsy in the past one year.Complete blood cell count showed mild anemia (Hbl08 g/L).The patient had an elevated high-sensitivity C reactive protein (86 mg/L)and erythrocyte sedimentation rate (46 mm/1h).White blood cells,pus cells and red blood cells were found on routine stool examination.Biochemical panel showed hypoalbuminemia (25.2 g/L),elevated transaminase (alanine aminotransferase 175 U/L,aspartate transaminase 229 U/L),hypertriglyceridemia (4.41 mmol/L),and hyperferritinemia (＞1 650.0 μg/L).Magnetic resonance enterography revealed the intestinal wall thickening and increased enhancement in parts of illeum and colon.Capsule endoscopy revealed multiple ulcers in jejunum.Colonoscopy showed multiple ulcers in colon and the pathological examination revealed chronic inflammation in mucosa of terminal ileum and colon,which was combined with partial necrosis and ulceration.Some phagocytes were seen in bone marrow smears.The patient was given multiple diagnoses,including hemophagocytic lymphohistiocytosis,Crohn's disease,sepsis,epilepsy,severe malnutrition,and hypoproteinemia.The pediatric Crohn's disease activity index (PCDAI)was 37.5.Genetic testing identified a hemizygotic mutation of c.910G＞T chrX:123022501 p.G304X in XIAP.The parents had no such mutation.The patient showed response to infliximab with oral intake of mercaptopurine and corticosteroids,and had remission with PCDAI of 0.There were 9 relevant articles (Chinese 0 English 9),which showed 33.3％ XIAP deficient patients manifested with inflammatory bowel disease(IBD),who might have other manifestations such as hemophagocytic lymphohistiocytosis or splenomegaly simultaneously or sequentially.Those patients showed poor response to monotherapy.Conclusion XIAP deficient patients have various clinical manifestations.Genetic testing is important to those male pediatric IBD patients who have the complicated symptoms or little response to standard therapy.