iDEND syndrome caused by KCNJ11 mutation unresponsive to sulfonylurea therapy: two case reports and literature review

Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes that predominantly manifests within the first six months of life. This report presents two patients with mutations in the potassium inwardly rectifying channel subfamily J member 11 ( KCNJ11 ) gene, accompanied by a narrative literature review. Both infants exhibited severe diabetic ketoacidosis (DKA) and growth retardation, without seizures. Following ketoacidosis resolution, Patient 1 required continuous subcutaneous insulin infusion (CSII) with continuous glucose monitoring (CGM), while Patient 2 received hospital-based point-of-care testing-guided multiple daily insulin injections supplemented with glibenclamide. However, both cases exhibited persistent non-responsiveness to sulfonylurea therapy. Genetic testing revealed a heterozygous KCNJ11 c.497G > A (p.Cys166Tyr) variant in both infants. Based on their clinical manifestations, both patients were diagnosed with iDEND. This paper presents a comprehensive account of the clinical features, varied insulin delivery methods, and glucose monitoring strategies in two patients with iDEND harboring the KCNJ11 c.497G > A variant. This finding expands the known clinical spectrum associated with this specific variant and provides critical evidence-based guidance for the therapeutic management.