17α羟化酶缺乏致46XY性发育异常:13例临床分析

17αhydroxylase deficiency induced 46XY disorder of sex development:a clinical analysis of 13 cases

目的:探讨社会性别为女性、染色体核型为46XY的17α羟化酶缺乏症(17OHD)的诊断及治疗。方法:回顾分析2006年1月至2023年1月就诊于郑州大学第一附属医院诊断为17OHD的社会性别为女性、核型为46XY的13例患者的临床资料。结果:13例17OHD患者的确诊平均年龄为(16.85±7.0)岁,确诊前外院漏诊、误诊5例。46XY的17OHD典型患者临床特点为第二性征不发育、原发性高促性腺激素性性腺功能低下性闭经、高血压、低血钾、皮质醇水平低、促肾上腺皮质激素(ACTH)水平高、肾上腺皮质增生、无子宫附件、骨龄落后于实际年龄。本研究中3例临床特征不典型患者通过P450c17(CYP17A1)基因检测确诊,1例为p.Thr329突变,1例p.Thr329和p.Thr307Ala复合突变。选择合适的糖皮质激素及性激素替代及手术可取得良好的预后。13例患者切除睾丸病理和未切除的睾丸影像学上均未发现恶性病变。结论:46XY 17OHD为罕见病,典型患者通过临床表现、辅助检查不难诊断,但有些患者并不具有典型临床表现,确诊年龄较晚。提示临床医生需提高对该疾病的认识,对于怀疑却临床特征不典型患者可通过P450c17(CYP17A1)基因检测确诊。对于青春期前渴望延迟睾丸切术者密切随访也未必不可接受,但安全性还需更多大量标本的积累。

Objective:To study the diagnosis and treatment of female(social gender)with 46XY 17αhydroxylase deficiency(17OHD).Methods:Retrospectively analyze the clinical data of those who were diagnosed as 17 alpha hydroxylase deficiency,the karyotype is 46XY while the social gender is female,from January 2006 to January 2023 in the First Affiliated Hospital of Zhengzhou university.Result:The average age of these 13 patients at diagnosis was(16.85±7.0)years,5 of them were missed diagnosis or misdiagnosis before definite diagnosis.Typical clinical characteristics of patients with 46XY 17αhydroxylase deficiency are lack of secondary sexual development,primary amenorrhoea with high gonadotrophin while low sex hormones,hypertension,hypokalemia,low level of cortisol,high ACTH level,adrenal cortex hyperplasia,no uterine and accessories,delayed bone age.Three patients were diagnosed by detection of P450c17(CYP17A1)gene in our research and we found one case with p.Thr329 mutation,and one case with p.Thr329 mutation and p.Thr307Ala compound mutation.Appropriate glucocorticoid and sex hormone replacement and surgery can achieve satisfactory prognosis.No diagnosis of malignancy among the 13 cases in this study,either the pathology of the resected testicles or the imaging of the un-resected testicles.Conclusion:46XY 17αhydroxylase deficiency are rare diseases,typical patients could be easily diagnosed by clinical manifestation and relevant examination,however,many patients do not have typical clinical manifestations,therefore,diagnose is delayed.This suggest that doctors should improve the understanding of this disease,for suspected patients but with atypical clinical features,detection of P450c17(CYP17A1)gene is suggested.Close follow-up it is probably feasible for adolescents who desire to delay resection of testis,but accumulation of a larger number of samples was needed in the future for the safety.