Song Yuqing, Lei Wenjie, Huang Qianqian, Zhang Jiehan, Zhang Qiao, Chen Lulu, Li Huiqing, Liu Li, Zeng Tianshu, Hu Xiang
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, 430022, People's Republic of China.
Diabetes Metab Syndr Obes. 2024 Nov 25;17:4389-4396. doi: 10.2147/DMSO.S481745. eCollection 2024.
Functional defects caused by mutations in the insulin receptor (INSR) gene often lead to severe hereditary insulin resistance syndromes, including but not limited to type A insulin resistance syndrome.
Here, we report a case of a 12-year-old girl with elevated fasting blood glucose detected by opportunistic testing, associated with severe insulin resistance and hyperandrogenemia. She had axillary hair, acne, clitoral hypertrophy, prominent labia minora hypertrophy and thickened voice with BMI 20.57kg/m, and ultrasound imaging showed that she had multiple follicles in both ovaries. Insulin was initially administered, but the glycemic control was poor. Accordingly, the prescription was later switched to metformin, maintaining euglycemic blood glucose level. The whole exome sequencing from peripheral blood revealed that the patient carries NM_000208.2:c.1225_1227delTTC (p.Phe409del) heterozygous mutation in the INSR gene. She was tentatively diagnosed as type A insulin resistance syndrome based on her clinical features and heterozygous mutation in the INSR gene.
Our results demonstrated that type A insulin resistance syndrome in patients presenting with severe insulin resistance and hyperandrogenemia was associated with a heterozygous variant of c.1225_1227delTTC (p.Phe409del), suggesting that exon sequencing would be beneficial to detect the potential mutations in the INSR gene of these patients for precise diagnosis and intervention in clinical practice.
胰岛素受体（INSR）基因突变引起的功能缺陷常导致严重的遗传性胰岛素抵抗综合征，包括但不限于A型胰岛素抵抗综合征。
在此，我们报告一例12岁女孩，通过机会性检测发现空腹血糖升高，伴有严重胰岛素抵抗和高雄激素血症。她有腋毛、痤疮、阴蒂肥大、小阴唇明显肥大及嗓音变粗，体重指数（BMI）为20.57kg/m²，超声成像显示双侧卵巢有多个卵泡。最初给予胰岛素治疗，但血糖控制不佳。因此，处方后来改为二甲双胍，维持血糖正常水平。外周血全外显子测序显示患者INSR基因存在NM_000208.2:c.1225_1227delTTC（p.Phe409del）杂合突变。根据其临床特征和INSR基因杂合突变，初步诊断为A型胰岛素抵抗综合征。
我们的结果表明，出现严重胰岛素抵抗和高雄激素血症的患者中的A型胰岛素抵抗综合征与c.1225_1227delTTC（p.Phe409del）杂合变异相关，提示外显子测序有助于检测这些患者INSR基因中的潜在突变，以便在临床实践中进行精确诊断和干预。
