两例X连锁肢端肥大性巨人症病例报道及致病基因检测  

Two case reports of X-linked acrogigantism and pathogenic gene detection

作　　者：梁寒婷 龚凤英 刘之慧 杨莹莹 姚勇[3] 王任直[3] 王林杰 陈美平 潘慧 陈博[4] 梁智勇[4] 冯逢[5] 朱惠娟 Liang Hanting;Gong Fengying;Liu Zhihui;Yang Yingying;Yao Yong;Wang Renzhi;Wang Linjie;Chen Meiping;Pan Hui;Chen Bo;Liang Zhiyong;Feng Feng;Zhu Huijuan(Department of Endocrinology,Key Laboratory of Endocrinology of National Health Commission,State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100730,China;Department of Endocrinology and Metabolism,The First Hospital of Shijiazhuang City,Shijiazhuang 050011,China;Department of Neurosurgery,Peking Union Medical College Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100730,China;Department of Pathology,Peking Union Medical College Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100730,China;Department of Radiology,Peking Union Medical College Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100730,China)

机构地区：[1]中国医学科学院,北京协和医学院,北京协和医院内分泌科,卫健委内分泌重点实验室,疑难重症及罕见病国家重点实验室,100730 [2]石家庄市第一医院内分泌科,050011 [3]中国医学科学院,北京协和医学院,北京协和医院神经外科,100730 [4]中国医学科学院,北京协和医学院,北京协和医院病理科,100730 [5]中国医学科学院,北京协和医学院,北京协和医院放射科,100730

出　　处：《中华内分泌代谢杂志》2022年第2期118-124,共7页Chinese Journal of Endocrinology and Metabolism

基　　金：国家重点研发计划(2016YFC0901501);中国医学科学院医学与健康科技创新工程(CAMS-2016-I2M-1-002)。

摘　　要：目的报告2例X连锁肢端肥大性巨人症(X-linked acrogigantism,X-LAG)患者的临床特点和诊治情况。方法回顾性报告2例患者临床资料并收集外周血进DNA行拷贝数变异检测。结果2例患者均为2岁起病,共同临床特点为线性生长加速、轻度肢大面容、手足增大、食欲增加、打鼾等巨人症表现。2例患者治疗前身高Z值分别为+6.86和+6.53,葡萄糖生长激素(growth hormone,GH)抑制试验示GH谷值均大于1 ng/mL,胰岛素样生长因子Ⅰ(insulin-like growth factor-Ⅰ,IGF-Ⅰ)分别为586.0 ng/mL和1042.0 ng/mL。患者1接受三程奥曲肽微球治疗后行手术,术后临床与生化均得到缓解。患者2接受兰瑞肽治疗5.5年,未达到生化缓解。通过拷贝数变异检测,2例患者胚系DNA均发现Xq26.3存在微重复,该区域含G蛋白偶联受体101(G-protein coupled receptor 101,GPR101)这一致病基因,诊为X-LAG。结论2岁以下婴幼儿出现生长加速等症状时需警惕X-LAG,药物联合手术治疗有效。Objective To report the clinical characteristics,diagnosis,and treatment of 2 cases of X-linked acrogigantism(X-LAG).Methods The clinical information of two patients were retrospectively reported,and peripheral blood DNA was collected for copy number variations detection.Results Both patients had onset at age of two,with common clinical characteristics including linear growth acceleration,mild facial coarsening,enlargement of hands and feet,increased appetite,and snoring,etc.The heights Z scores of the two patients before treatment were+6.86 and+6.53,respectively.Growth hormone(GH)glucose inhibition test showed that GH nadir values were over 1 ng/mL and insulin-like growth factor-Ⅰ(IGF-Ⅰ)were 586.0 ng/mL and 1042.0 ng/mL,respectively.Patient 1 received three cycles of octreotide microspheres therapy followed by surgery,and achieved clinical and biochemical remission.Patient 2 had lanreotide for 5.5 years but failed biochemical remission.Microduplication of Xq26.3,which contained pathogenic gene G-protein coupled receptor 101(GPR101),was found in germline DNA of two patients through copy number variation detection,leading to the diagnosis of X-LAG.Conclusion It should be cautious of X-LAG when children below 2 years old presents symptoms such as overgrowth and so on.Medication combined with surgery is effective.

关 键 词：X连锁肢端肥大性巨人症 生长激素腺瘤 GPR101 微重复 

分 类 号：R584.11[医药卫生—内分泌] R736.4[医药卫生—内科学]