Abstract: Objective    To analyze the clinical features and molecular genetic changes of congenital adrenal hyperplasia（CAH） with non-21 -OHD，and to investigate the correlation between clinical phenotype and genotype of different types of CAH. Methods    A total of 60 patients diagnosed with congenital adrenal hyperplasia were collected from Endocrinology Department of Children′s Hospital of Zhejiang University School of Medicine from July 2017 to April 2022. There were 22 cases of CAH with non 21-OHD. Clinical manifestation，laboratory examination and gene testing results were retrospectively analyzed. Results    Among the 60 CAH patients diagnosed by clinical manifestations and genetic diagnosis，22 were non-21-OHD patients，of whom 11 （11/22） were girls and 11 （11/22） were boys，aged from 19 days to 14.5 years. There were 8 cases of 11β-hydroxylase deficiency （11β-OHD） （8/22），7 cases of 17α-hydroxylase deficiency （17α-OHD） （7/22），5 cases of congenital lipoid adrenal hyperplasia （CLAH）（5/22），and 1 case of P450 oxidoreductase deficiency （PORD）（1/22）；1 case Of 3β -hydroxysteroid dehydrogenase type 2 deficiency （3βHSD2D）（1/22）. External genital dysplasia and pigmentation were found in all 5 types of diseases，and the age of diagnosis in the 17α-OHD group was the latest. Among the 5 related genes （CYP11B1，CYP17A1，StAR，POR，HSD3B2） found in 22 patients，a total of 28 gene mutations were detected，including 10 new mutations that had not been reported before （CYP11B1 gene c.715_731del，c.240-2A>G ，c.1359dupG，c.64C>T，c.346T>C，chr8:143957113-143994301 ，chr8：143957206-143994456 fragment deletion， CYP17A1 gene c.1304T>C，StAR gene c.491C>A，HSD3B2 gene c.484G>A ）. The c.1459_1467del （p.D487_F489del） with the highest frequency accounted for 50% （7/14） of CYP17A1 alleles. Conclusion    Genetic testing is important for the early diagnosis and treatment of non-21-OHD. The detection rate of 17α-OHD is close to that of 11β-OHD. And p.D487_F489del and p.Y329Kfs are the main variants in the study. A homozygous mutation of c.484G>A （P.Glu162Lys） is found in 3β-hydroxysteroid dehydrogenase type 2 deficiency，which has not been previously reported.

Key words: 11β-hydroxylase deficiency, 17α-hydroxylase deficiency, congenital lipoid adrenal hyperplasia, P450 oxidoreductase deficiency, 3β-hydroxysteroid dehydrogenase type 2 defificiency

摘要： 目的    分析非21-羟化酶缺乏症（hydroxylase deficiency，OHD）的先天性上腺皮质增生生症（CAH）临床特征及分子遗传学改变，探讨不同类型CAH的临床表型与基因型相关关系。方法    收集于浙江大学医学院附属儿童医院内分泌科2017年7月至2022年4月期间就诊并基因确诊为CAH的患儿60例，其中非21-OHD的CAH患儿22例，回顾性分析其临床表现、实验室结果和基因检测结果。结果    通过临床表现和基因诊断的22例非21-OHD患儿，其中女童11例，男童11例，年龄19 d到14.5岁。11β-OHD 8例（8/22）；17α-OHD 7例（7/22）；先天性类脂性肾上腺皮质增生症（congenital lipoid adrenal hyperplasia，CLAH）5例（5/22）；P450氧化还原酶缺乏症（P450 oxidoreductase deficiency，PORD）1例（1/22）；3β-羟类固醇脱氢酶2型缺乏症（3β-hydroxysteroid dehydrogenase type 2 defificiency，3βHSD2D）1例（1/22）。5类疾病均有外生殖器发育异常及色素沉着表现，其中17α-OHD组确诊年龄最大，22例患儿发现5种CAH相关基因（CYP11B1、CYP17A1、StAR、POR、HSD3B2），共检测到28种基因变异，其中发现10个未报道过的新变异（CYP11B1基因c.715_731del，c.240-2A>G，c.1359dupG，c.64C>T，c.346T>C，chr8:143957113-143994301，chr8：143957206-143994456片段缺失；CYP17A1基因c.1304T>C；StAR基因c.491C>A；HSD3B2基因c.484G>A），出现频率最高的c.1459_1467del（p.D487_F489del）占CYP17A1等位基因的50%。结论    基因检测在早期诊断和治疗非21-OHD中具有重要作用。17α-OHD症检出率与11β-OHD症相仿，且发现p.D487_F489del和p.Y329Kfs是研究主要变异类型。3βHSD2D中发现1个c.484G>A（p.Glu162Lys）纯合突变，该突变既往未见有报道。

关键词: 11β-羟化酶缺乏症, 17α-羟化酶缺乏症, 类脂性先天性肾上腺皮质增生症, P450氧化还原酶缺乏症, 3β-羟类固醇脱氢酶2型缺乏症