儿童原发性肾上腺皮质功能减退症罕见病因:13例临床特征及基因突变分析  

Analysis of clinical manifestations and gene mutations of 13 child patients with rare causes of primary adrenal insufficiency

作　　者：侯乐乐[1] 林少汾 刘祖霖[1] 欧辉[1] 张丽娜[1] 江转南 孟哲[1] 梁立阳[1] Hou Lele;Lin Shaofen;Liu Zulin;Ou Hui;Zhang Lina;Jiang Zhuannan;Meng Zhe;Liang Liyang(Department of Pediatrics,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510288,China)

机构地区：[1]中山大学孙逸仙纪念医院(南院区)儿科,广州510288

出　　处：《中华内分泌代谢杂志》2019年第1期15-20,共6页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的分析罕见病因所致儿童原发性肾上腺皮质功能减退症(primary adrenal insufficiency,PAI)的临床特征和基因突变类型,提高临床医生对该病的认识。方法回顾性分析本院儿科2010年9月至2017年8月诊治的PAI患儿临床表现、实验室检查、基因检测结果,排除先天性肾上腺皮质增生症、以神经系统起病或明确家族史的X连锁肾上腺脑白质营养不良、自身免疫性。肾上腺皮质功能减退症等病因。结果在13例患儿中有12例男性、1例女性,中位年龄为3岁10个月,初诊时临床表现按发生率高低依次为皮肤黏膜色素沉着、失盐危象或电解质紊乱、胃肠道症状和疲乏等,外生殖器均发育正常,血清皮质醇均降低,ACTH均明显升高,部分患儿存在醛固酮、肾素活性降低,17-羟孕酮、雄烯二酮、睾酮在正常范围,部分患儿骨龄落后、肾上腺萎缩。13例患儿共发现3种基因突变,其中9例为NROB1基因突变,3例为ABCD1基因突变,均为明确致病突变,与临床特征相符;1例为CYP11A1基因杂合突变,不能完全解释临床特征。结论儿童PAI存在皮肤色素沉着、电解质紊乱等肾上腺皮质功能减退常见表现,但缺乏特异性,遗传学检查对于明确病因和判断预后具有重要作用,在儿童罕见病因PAI中NROB1和ABCD1基因突变较为常见。Objective To analyze the clinical manifestations and gene mutations of rare causes of primary adrenal insufficiency (PAI)in childhood.Methods The clinical features,laboratory tests and gene mutation of 13 patients with PAI in our hospital from September 2010 to August 2017 were analyzed retrospectively.Patients with congenital adrenal hyperplasia,X-linked adrenoleukodystrophy with neurological onset or a clear family history,and autoimmune adrenal insufficiency were excluded.Results The median age of 13 cases (12 males,1 female)was 3 years and 10 months.Medical history or clinical manifestations on the first visit included hyperpigmentation, electrolyte imbalance/sah-wasting crisis,gastrointestinal symptoms,and fatigue,etc.All developments of external genitalia were normal.All cases presented with decreased serum cortisol and increased ACTH levels.Some of the cases showed decreased aldosterone level and plasma renin activity,while 17α-hydroxyprogesterone,testosterone,and androstenedione were in the normal range.Part of cases revealed delayed bone age and adrenal atrophy.Three gene mutations were detected in 13 patients,including NROB 1 gene (9/13),ABCD1 gene (3/13),and CYP 11A1 gene (1/13).NROB1,and ABCD1 gene mutations were pathogenic mutations,consistent with clinical characteristics. CYPllA1 gene mutation was heterozygote,which cannot fully explain the clinical features.Conclusion PAI in childhood presents common clinical manifestations of adrenal insufficiency,e.g.hyperpigmentation and electrolyte imbalance/salt-wasting crisis,but without specificity.Gene mutational analysis is necessary for precise diagnosis and prognosis estimation.NROB 1 and ABCD1 gene mutations were common in childhood with rare causes of PAL.

关 键 词：原发性肾上腺皮质功能减退症 NROB1基因 突变 儿童 

分 类 号：R725.8[医药卫生—儿科]