DAX1/NROB1基因突变所致X连锁先天性肾上腺发育不良临床分析

目的 分析经基因测序确诊的9例X连锁的先天性肾上腺发育不良(AHC)患者的临床特点,为诊断提供依据.方法 2007年7月至2009年6月在北京协和医院就诊的9例X连锁的AHC患者,回顾性分析患者的临床表现、血生化检查和激素测定,包括黄体生成素释放激素(LHRH)兴奋试验和人绒毛膜促性腺激素(HCG)兴奋试验以明确性腺功能,及肾上腺CT检查,并行基因测序.结果 9例患者来自8个家系,基因检测均有DAX1/NR0B1基因突变.主要临床特点为:(1)部分患者(3个家系)有X连锁隐性遗传的家族史;(2)发病年龄均＜10岁(2个月～9岁),在我院就诊年龄15～34岁;(3)均有肾上腺皮质功能低减的表现,但表现不同.主要为:色素沉着(9例),恶心、呕吐(8例),低血压(6例),肾上腺皮质危象(4例),其他有:乏力、低血糖、易感冒等;实验室检查:发病时均有低钠血症,血ACTH高于正常,血17-OHP低于正常;(4)均无青春发育,LHRH兴奋试验无反应,其中部分患者(3例)HCG兴奋试验正常;(5)CT提示双肾上腺细小.结论 X连锁的AHC临床上主要表现为肾上腺皮质和性腺功能低减,但不同患者临床表现差别大,因此对于男性儿童肾上腺皮质功能低减症患者,应管惕X连锁的AHC,需进行DAX1/NR0B1基囚检测并随访患者的性腺发育情况.

Clinical features of 9 patients with X-linked adrenal hypoplasia congenita caused by DAX1/NR0B1 gene mutations

Objective To study the clinical features of 9 patients with X-linked adrenal hypoplasia congenita (AHC) by gene sequencing so as to provide diagnostic rationales. Methods The patients were 9 cases of X-linked AHC treated at our hospital from July 2007 to June 2009. The clinical manifestations were analyzed. The blood biochemistry tests and the hormone examinations including luteinizing hormone-releasing hormone ( LHRH) stimulation tests and human chorionic gonadotropin ( HCG) stimulation tests were conducted to evaluate the functions of gonads. And CT scans of adrenal glands and gene tests of DAX1/ NR0B1 were performed. Results Nine AHC patients from 8 families were studied. All patients had DAX1/ NR0B1 gene mutations. The main clinical features were; (1) some patients (3 families) had a family history of X-linked recessive inheritance; (2) the ages of onset were all below 10 years old (from 2 month after birth to 9 years old) and ages of being treated at our hospital were from 15 to 34 years old; (3) all patients had adrenocortical hypofunctions, but clinical situations were different, most of them had pigmentation (n = 9) , nausea and vomiting (n = 8) , hypotension (n = 6) , Addisonian crisis (n =4). Others were debility, hypoglycemia and cold susceptibility. laboratory tests indicated that all patients had hyponatremia at the onset and higher blood adrenocorticotropic hormone level, lower blood 17hydroxyprogesterone level compared to normal controls; (4) none of the patients had puberty and there was no responses to LHRH stimulation tests, 3 of them had normal responses to HCG stimulation tests; (5) small bilateral adrenal glands were displayed on CT scans. Conclusions The main clinical features of Xlinked AHC are adrenocortical hypofunetion and hypogonadotropic hypogonadism. But the phenotypes vary greatly in different patients. So male children with adrenal cortical hypofunetion should be suspected of Xlinked AHC and DAX1/NR0B1 gene tests should be performed. The sexual development of the patients also should be followed up.