摘要
目的分析先天性低促性腺激素性性腺功能减退(CHH)男童的临床及遗传学特征。方法横断面研究,回顾性分析。收集2019年12月至2023年2月在深圳市儿童医院内分泌专科就诊,最后基因确诊为CHH的27例男性患儿的临床资料、实验室数据及基因结果。分析其临床表现、激素水平及其基因变异情况。非正态分布采用中位数表示,非正态分布数据两组间比较采用秩和检验。结果基因确诊为CHH男性患儿共27例,初诊年龄为0.3~16.6岁,患儿均表现为小阴茎(占100%),合并隐睾16例(占59.3%),合并小睾丸9例(占33.3%),单纯性小阴茎7例(占25.9)%,无单纯性隐睾,3例患儿合并心脏异常;基础血清黄体生成素(LH)水平中位数为0.09 IU/L,92.5%(25/27)的患儿基础LH<1.00 IU/L,促性腺激素释放激素(GnRH)兴奋后LH峰值的中位数为1.42 IU/L,96.2%(26/27)的患儿LH峰值<4.00 IU/L;血清抑制素B的中位数为41.15μg/L;血清抗苗勒管激素(AMH)的中位数为12.62 mg/L;合并隐睾的患儿血清AMH水平明显低于非隐睾患儿(10.02 mg/L比50.50 mg/L,P<0.05);27例患儿共检出12种基因变异,其中1例为双基因变异,最常见的基因变异为CHD7基因及ANOS1基因(各7例,二者共占51.8%),其次为FGFR1基因变异3例(占11.1%)。4例患儿短期给予GnRH泵或重组人卵泡刺激素皮下注射,治疗后血清抑制素B及AMH水平较治疗前明显增加,且睾丸容积较治疗前增大。结论CHH是先天性疾病,不同年龄临床表现不同,儿童期主要表现为小阴茎及隐睾,部分患儿存在小睾丸,青春前期确诊较困难,基因检测对早期诊断具有重要意义。
Objective To analyze the clinical and genetic characteristics of congenital hypogonadotropic hypogonadism(CHH)in boys.Methods Cross-sectional study.Clinical data,laboratory data and genetic results of boys who were genetically diagnosed with CHH at the Department of Endocrinology of Shenzhen Children′s Hospital from December 2019 to February 2023 were collected in this retrospective study.Their clinical manifestations,hormone levels and gene mutations were analyzed.The non-normal distribution was represented by the median.The rank sum test was used to compare the non-normal distribution data between the two groups.Results A total of 27 boys were genetically diagnosed with CHH,with the age at first diagnosis ranging from 0.3 to 16.6 years old.All these children presented with micropenis(100%),of whom 16 were complicated with cryptorchidism(59.3%),9 with microrchidia(33.3%),7 with simple micropenis(25.9%),and no had simple cryptorchidism.Three children had cardiovascular dysplasia.The median of basal luteinizing hormone(LH)level was 0.09 IU/L,and 92.5%(25/27)of children had the basal LH level below 1.00 IU/L.The median of peak LH level after gonadotropin-releasing hormone(GnRH)stimulation was 1.42 IU/L,and 96.2%(26/27)of children had the peak LH level below 4.00 IU/L.The median of serum inhibin B was 41.15μg/L,and the median of serum anti-Müllerian hormone(AMH)was 12.62 mg/L.The serum AMH level of children with cryptorchidism was significantly lower than that of children without cryptorchidism(10.02 mg/L vs.50.50 mg/L,P<0.05).A total of 12 gene mutations were detected in the 27 children,of which 1 was biallelic mutation.The most common gene mutations were in CHD7 and ANOS1 genes(7 children each,both accounting for 51.8%),followed by FGFR1 gene(3 children,11.1%).After short-term treatment by GnRH pump or subcutaneous injection of recombinant human follicle stimulating hormone in 4 children,the levels of serum inhibin B and AMH increased significantly,and the testicular volume also increased.Conclusions CHH is a congenital disease with different clinical manifestations at different ages.The main manifestations in childhood are micropenis and cryptorchidism,and some children have microrchidia.Its diagnosis in prepuberty is difficult,but genetic testing is of great significance for early diagnosis.
作者
焦燕华
张龙江
苏喆
潘丽丽
刘霞
赵岫
Jiao Yanhua;Zhang Longjiang;Su Zhe;Pan Lili;Liu Xia;Zhao Xiu(Department of Endocrinology,Shenzhen Children′s Hospital,Shenzhen 518000,China)
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2024年第3期187-192,共6页
Chinese Journal of Applied Clinical Pediatrics
