J Clin Res Pediatr Endocrinol. Ahead of Print: JCRPE-49389 | DOI: 10.4274/jcrpe.galenos.2024.2024-2-14

Hereditary Severe Insulin-resistance Syndrome and Acanthosis Nigricans Caused by Novel Mutations in the INSR Gene

Chen Chongyang¹, Zhao Yangting¹, Li Kai¹, Lv Xiaoyu¹, Wang Yawen¹, Zhen Donghu³, Fu Songbo³, Ma Lihua², Zhou Liyuan², Liu Jingfang^3
1The First Clinical Medical College,Lanzhou University, Lanzhou,Gansu, China
²Department of Endocrinology, the First Hospital of Lanzhou University, Lanzhou,Gansu,China
³The First Clinical Medical College,Lanzhou University, Lanzhou,Gansu, China and Department of Endocrinology, the First Hospital of Lanzhou University, Lanzhou,Gansu,China

Most cases associated with Hereditary Severe Insulin Resistance Syndrome (H-SIRS) are linked to mutations in the insulin receptor (INSR) gene. Patients with H-SIRS typically manifest symptoms of hyperinsulinemia, insulin resistance, and diabetes mellitus. Other symptoms include impaired glucose regulation, hyperandrogenism, and the presence of acanthosis nigricans (AN). In this report, we present two cases of H-SIRS in female children exhibiting various symptoms, such as hyperinsulinemia, fasting hypoglycemia, postprandial hyperglycemia, overweight, fatty liver, hyperandrogenism, and varying degrees of AN. One patient also presented with mental retardation. Gene sequencing identified specific mutations in the INSR gene for both patients: c.2663A > G (p.Tyr888Cys) and c.38_61del (p.Pro13_Ala20del). These mutations have the potential to disrupt the interaction between INSR and insulin, leading to abnormal insulin signaling, insulin resistance, and various clinical manifestations.

Keywords: Insulin receptor, insulin resistance, hyperinsulinemia, hyperandrogenism, impaired glucose regulation; acanthosis nigricans

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