Clinical characteristics of adolescent cases with Type A insulin resistance syndrome caused by heterozygous mutations in the β‐subunit of the insulin receptor (INSR) gene: 胰岛素受体(INSR)基因β亚基杂合突变所导致A型胰岛素抵抗综合征的青少年病例临床特征. Issue 1 (4th July 2018) - Takasawa, Kei
Abstract: Background: Type A insulin resistance (IR) is a rare form of severe congenital IR that is frequently caused by heterozygous mutations in the insulin receptor ( INSR ) gene. Although Type A IR requires appropriate intervention from the early stages of diabetes, proper diagnosis of this disease is challenging, and accumulation of cases with detailed clinical profiles and genotypes is required. Methods: Herein we report on six peripubertal patients with clinically diagnosed Type A IR, including four patients with an identified INSR mutation. To clarify the clinical features of Type A IR due to INSR mutation, we validated the clinical characteristics of Type A IR patients with identified INSR mutations by comparing them with mutation‐negative patients. Results: Four heterozygous missense mutations within the β‐subunit of INSR were detected: Gly1146Arg, Arg1158Trp, Arg1201Trp, and one novel Arg1201Pro mutation. There were no obvious differences in clinical phenotypes, except for normal lipid metabolism and autosomal dominant inheritance, between Type A IR due to INSR mutations and Type A IR due to other factors. However, our analysis revealed that the extent of growth retardation during the fetal period is correlated with the severity of insulin signaling impairment. Conclusions: The present study details the clinical features of four patients with genetically proven Type A IR. Further accumulation of genetically proven cases and long‐term treatment prognoses following early diagnosis are required to further elucidate the dynamics of this disease. Abstract : Highlights This study presents details of six peripubertal cases with clinically diagnosed Type A insulin resistance (IR), including four cases with identified insulin receptor ( INSR ) gene mutations (three previously reported and one novel). The study reveals the clinical features of patients with Type A IR due to INSR mutations compared with mutation‐negative patients, and indicates that the extent of growth retardation during the fetal period is correlated with the severity of insulin signaling impairment.