A novel presentation of a His1157Arg INSR mutation in male half-siblings with type A insulin resistance: A case report

Type A insulin resistance, a rare disorder resulting from mutations in the INSR gene, exhibits a wide range of clinical presentations. We report two male half-siblings with a His1157Arg missense mutation in exon 19 of the INSR gene. Patient 1 presented with hyperglycemia and features resembling type 1 diabetes, without acanthosis nigricans. In contrast, patient 2 exhibited characteristics typically seen in children diagnosed with type 2 diabetes, including obesity and acanthosis. Genetic testing confirmed the shared pathogenic mutation. Their divergent phenotypes underscore the heterogeneity of type A insulin resistance and highlight the critical role of genetic testing in atypical diabetes cases. Targeted therapy with metformin, glucagon-like peptide-1 receptor agonists, and sodium-glucose co-transporter 2 inhibitors improved glycemic control in both patients.