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目的通过IL-10RA基因突变导致的炎症性肠病(IBD)病例,进一步深化认识极早发型IBD(VEO-IBD)的特点。方法报告1例VEO-IBD临床诊断(症状、体征和肠镜),全外显子组测序(WES)明确病因,脐血干细胞移植精准治疗的过程。结果患儿,女,44 d,足月,生后8 d始腹泻呈进行性加重(多至每天10~20次),持续间断发热,重度营养不良。患儿姐姐1月龄反复发热、腹泻和鹅口疮,5月龄时疑尿道瘘不治死亡。入复旦大学附属儿科医院4 d外阴皮肤红肿,渐形成肛瘘,体重2.6 kg。肠镜示直肠黏膜增生性病变,乙状结肠、降结肠可见纵行溃疡和鹅卵石样增生。予抗感染、沙利度胺6 mg·d~(-1)和美沙拉秦150 mg·d~(-1)控制肠道炎症反应,肠道内外营养支持等对症治疗。行WES明确为IL-10RA基因缺陷,获得同性别无关供者HLA基因位点8/10的脐血行干细胞移植。移植后12周嵌合体率95.7%,Sanger测序及蛋白功能验证IL-10RA基因突变点被修复,IL-10信号通路轴功能恢复正常。患儿大便逐渐成型,体重5.2 kg,结肠镜显示肠黏膜愈合,仅见少量增生和疤痕,移植后10个月大便钙卫蛋白72μg·g~(-1)。结论脐血干细胞移植作为治疗IL-10RA基因突变导致的VEO-IBD方法,值得积累更多的病例。
Objective To further understand the characteristics of very early-onset IBD (VEO-IBD) through the case of inflammatory bowel disease (IBD) caused by IL-10RA mutation. Methods One case of VEO-IBD clinical diagnosis (symptoms, signs and colonoscopy), the whole exome sequencing (WES) a clear cause, umbilical cord blood stem cell transplantation for the precise treatment of the process. Results The incidence of diarrhea in infants and females was 44 days, term term and 8 days after birth. The diarrhea was progressive (up to 10 ~ 20 times a day), with intermittent fever and severe malnutrition. Children with fever, fever, diarrhea and thrush in 1 month old children died of urethral fistula at 5 months of age. Into the Fudan University pediatric hospital 4 d vulva skin swelling, gradually formed anal fistula, weight 2.6 kg. Colonoscopy showed rectal mucosal hyperplastic lesions, sigmoid colon, descending colon can be seen longitudinal ulcers and pebbles-like hyperplasia. Anti-infection, Thalidomide 6 mg · d ~ (-1) and Mesalazine 150 mg · d ~ (-1) control the intestinal inflammation, intestinal nutrition support and other symptomatic treatment. Line WES was identified as a defect in IL-10RA gene and cord blood stem cell transplantation was obtained in 8/10 HLA-identical loci of the same sex-unrelated donor. At 12 weeks post-transplantation, the chimerism rate was 95.7%. Sanger sequencing and protein function validation demonstrated that the IL-10RA gene mutation site was repaired and IL-10 signaling pathway axis function returned to normal. Children stool was gradually formed, weighing 5.2 kg, colonoscopy showed intestinal mucosal healing, only a small amount of proliferation and scar see, 10 months after transplantation fecal calprotectin 72μg · g ~ (-1). Conclusion Umbilical cord blood stem cell transplantation as a VEO-IBD method for the treatment of mutations in the IL-10RA gene deserves to accumulate more cases.