罕见儿童遗传性肾上腺疾病的临床特征及类固醇激素的质谱测定  

Clinical characteristics and LC-MS/MS method for measurement of steroid hormones in rare type of hereditary adrenal disease in children

作　　者：杨海花[1] 黄爱 李园[1] 陈琼[1] 刘英[1] 卫海燕[1] YANG Hai-hua;HUANG Ai;LI Yuan;CHEN Qiong;LIU Ying;WEI Hai-yan(Dapartment of Endocrinology,Genetics and Metabolism,Henan Children's Hospital,Zhengzhou Children's Hospital,Zhengzhou 450018,China)

机构地区：[1]郑州大学附属儿童医院内分泌遗传代谢科,郑州450018

出　　处：《医药论坛杂志》2024年第7期673-678,683,共7页Journal of Medical Forum

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20210625)。

摘　　要：目的总结6例儿童遗传性肾上腺疾病的临床特征及类固醇激素的质谱测定,分析液相色谱-串联质谱(liquid chromatography-tandem mass spectrometry,LC-MS/MS)技术检测类固醇激素在临床应用中的优势和不足。方法分析2020年5月—2022年3月在河南省儿童医院就诊的基因诊断明确的6例罕见儿童遗传性肾上腺疾病患儿的临床特征及类固醇激素水平。结果6例患儿经基因检测均诊断明确,分别为:11β羟化酶缺陷症(11β-OHD)、17α羟化酶缺陷症(17α-OHD)、21羟化酶缺陷症(21-OHD)、细胞色素P450氧化还原酶缺陷症(PORD)、类脂性先天性肾上腺皮质增生症(LCAH)、X-连锁肾上腺发育不良(X-linked adrenal hypoplasia congenita,AHC),6例患儿中社会性别男性2例,女性4例,患儿就诊年龄1月20天~10岁,11β-OHD和PORD患儿因“阴蒂肥大”就诊,21-OHD患儿因“生长加速、变声、发现睾丸肿物”就诊,17α-OHD患儿因“高血压”就诊,LCAH患儿因“皮肤黄染”就诊,AHC患儿因“皮肤黏膜色素沉着”就诊,采用LC-MS/MS技术检测类固醇激素,发现11β-OHD表现为11-脱氧皮质醇、11-脱氧皮质酮明显升高,17α-羟孕酮(17α-hydroxyprogesterone,17-OHP)轻度升高,17α-OHD表现为孕烯醇酮、孕酮、11-脱氧皮质酮、11脱氧皮质醇、皮质酮升高,17-OHP、皮质醇、雄烯二酮、脱氢表雄酮降低,21-OHD表现为21-脱氧皮质醇、17-OHP、睾酮、雄烯二酮、17羟孕烯醇酮明显升高,皮质醇降低,PORD表现为孕酮、17-OHP、11脱氧皮质醇、21-脱氧皮质醇升高,睾酮不高,LCAH表现为类固醇激素均降低,AHC则出现11-脱氧皮质醇、11-脱氧皮质酮、雄烯二酮略升高,皮质醇正常,基因检测结果分别为:CYP11B1 c.1385T>C(p.L462P)和c.64C>T(p.Q22*)复合杂合突变、CYP17A1 c.985_987delinsAA(p.Y329Kfs*90)纯合突变、CYP21A2 c.293-13A/C>G(I2G)和c.1451_1452delinsC(p.R484Pfs*58)复合杂合突变、POR c.1370G>A(p.R457H)纯合突变、StAR c.465+2T>A和c.229C>T(p.QObjective Summarize the clinical characteristics and liquid chromatography tandem-mass spectrometry(LC-MS/MS)method for the measurement of steroid hormones in 6 cases of hereditary adrenal diseases in children,and analyze the advantages and disadvantages of LC-MS/MS method in detecting steroid hormones in clinical applications.Methods We retrospectively analysed the clinical data of 6 cases of rare adrenal disease admitted to Henan Children's Hospital and summarized their clinical manifestations,auxiliary examinations,diagnosis and mutational spectrum from May 2020 to March 2022.Results Through gene sequencing,they were diagnosed as 11-β Hydroxylase deficiency(11β-OHD),17α-Hydroxylase deficiency(17α-OHD),21 hydroxylase deficiency(21-OHD),cytochrome P450 oxidoreductase deficiency(PORD),lipoid congenital adrenal hyperplasia(LCAH)and X-linked adrenal hypoplasia congenita(AHC)respectively.Among the 6 patients,2 were male and 4 were female.Their diagnosed age was from 1 month and 20 days to 10 years.The children with 11β-OHD and PORD were admitted to department because of the clitorism.The children with 21-OHD,17-OHD,LCAH and AHC were urged to clinic due to“accelerated growth,vice broke,and testicular mass”,“hypertention”,“jaundice”and“pigmentation”respectively.Steroid hormones were detected by LC-MS/MS,and 11β-OHD showed that 11-deoxycortisol and 11-deoxycorticosterone increased significantly,17α-Hydroxyprogesterone(17α-Hydroxyprogesterone,17 OHP)slightly increased,17α-OHD showed the increase of pregnenolone,progesterone,11-deoxycorticosterone and corticosterone,the decrease of 17-OHP and cortisol,21-OHD showed the obvious increase of 21-deoxycorticosterone,17-OHP,testosterone,androstenedione and 17-hydroxypregnenolone,PORD showed the increase of progesterone,17-OHP and 21-deoxycorticosterone,testosterone was in normal range,LCAH shows the decrease of all steroid hormones.The child with AHC showed the 11-deoxycortisol,11-deoxycorticosterone and androstenedione increased slightly,and he had no

关 键 词：液相色谱-串联质谱 类固醇激素 基因检测 儿童 肾上腺 

分 类 号：R586[医药卫生—内分泌]