摘要：
Objective To analyze the clinical and molecular genetic characterizations of X-linked adrenal dysplasia congenita(AHC) onset in infant.Methods Seven children (from 7 families) with X-linked AHC who were admitted to the Department of Endocrinology,Genetics and Metabolism,Children's Hospital Affiliated to Zhengzhou University,from July 2012 to June 2017 were selected.All patients were screened for dosage-sensitive-sex reversal-adrenal hypoplasia congenital critical region on the X chromosome gene1 (DAX1/NR0B1) mutations.The clinical manifestation and laboratory examination were analyzed,their clinical characterizations were summarized.Results Seven patients were all male,the onset age of the patients were from after birth to 7 months old,and 4 patients (4 families) had a family history of X-linked recessive inheritance.The clinical manifestations were skin pigmentation [100.0％ (7/7 cases)],vomiting [71.4％ (5/7 cases)],no weight gain [57.1％ (4/7 cases)] and poor spirit [28.6％ (2/7 cases)].Laboratory tests showed that hyperkalemia and hyponatremia,increased coricotrophin,normal or decreased cortisol,17α-hydroxyprogesterone,progesterone,aldosterone and dehydroepiandrosterone.Testosterone levels increased in 5 patients.The abnormalities of adrenal glands imaging could be seen in 2 patients.Two patients were misdiagnosed as congenital adrenal cortical hyperplasia.Then the definitive diagnosis were made by genetic test.DAX1/ NR0B1 gene mutations were found in all patients.Five patients were novel mutations (c.114_126del,c.872G ＞ A,c.56delG,c.884T ＞ G,c.1217delG).Conclusions The clinical manifestations of X-linked AHC with infant onset include pigmentation,poor spirit and growth retardation,which should be differentiated from congenital adrenal cortical hyperplasia.Hormone levels such as elevated blood 17α-hydroxyprogesterone and family history are the main identification points,and AHC cannot be excluded when testosterone level increases.Five novel mutations are found in this study,which enrich the gene database.%目的 分析婴儿起病的X连锁先天性肾上腺发育不良(AHC)的临床及分子遗传学特点.方法 选取2012年7月至2017年6月在郑州大学附属儿童医院内分泌遗传代谢科就诊的7例X连锁AHC患儿,患儿均检测剂量敏感-性逆转-肾上腺增生不良基因1(DAX1/NR0B1)基因突变,回顾性分析患儿的临床表现、实验室检查结果,总结其临床特点.结果 7例患儿均为男性,婴儿期(0～7个月)起病,其中4例有X连锁隐性遗传家族史.起病表现为皮肤色素沉着[100.0％(7/7例)]、呕吐[71.4％(5/7例)]、体质量不增[57.1％(4/7例)]、精神差[28.6％(2/7例)]等.实验室检查:电解质紊乱(高钾、低钠),促皮质素升高,皮质醇、17αt-羟孕酮、孕酮、醛固酮、硫酸脱氢表雄酮正常或降低;5例患儿睾酮水平升高,2例患儿肾上腺影像学异常.2例患儿病初误诊为先天性肾上腺皮质增生症,最终完善基因检测明确诊断.7例患儿均检测到DAX1/NR0B1基因突变,其中5例为未经报道的突变,分别为c.114_126del、c.872G＞A、c.56delG、c.884T＞G及c.1217delG.结论 婴儿起病的X连锁AHC患儿临床主要表现为色素沉着、精神差、生长迟缓,需与先天性肾上腺皮质增生症相鉴别,血液17α-羟孕酮等激素水平及家族史是其主要鉴别点,睾酮水平增高不能排除AHC.5例新发突变丰富了基因数据库.
