Yuqing Song,1,2,* Wenjie Lei,1– 3,* Qianqian Huang,1,2 Jiehan Zhang,1,2 Qiao Zhang,4 Lulu Chen,1,2 Huiqing Li,1,2 Li Liu,5 Tianshu Zeng,1,2 Xiang Hu1,2 

1Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, 430022, People’s Republic of China; 3People’s Hospital of Luotian County, Huanggang, 438600, People’s Republic of China; 4Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5The People’s Hospital of Maojian, Shiyan, 442000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Tianshu Zeng; Xiang Hu, Email tszeng@126.com; huxiang628@126.com

Background: 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.
Method and Result: 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/m2, 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.
Conclusion: 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.

Keywords: insulin receptor gene, heterozygous mutation, severe insulin resistance, hyperandrogenemia, type A insulin resistance syndrome, female