Permanent Neonatal Diabetes with High Insulin Requirements Due to a New Variant in the INS Gene

Neonatal diabetes is an infrequent disorder that may present as transient, permanent, or syndromic. It is most commonly caused by pathogenic variants involving the ABCC8, KCNJ11, and INS genes. To describe a neonate with permanent diabetes mellitus due to a previously unreported variant in the INS gene, outlining the diagnostic complexities, therapeutic interventions, and related clinical challenges. Neonate with symmetrical intrauterine growth restriction, who presented severe hyperglycemia not associated with ketosis or infectious. He had high insulin requirements and did not respond to sulfonylurea management. Anti-insulin and anti-islet pancreatic antibodies were negative. Genetic sequencing revealed a homozygous missense variant (c.3G>A, p.Met1Ile) in the INS gene, which had not been previously reported in the literature.
Timely molecular diagnosis of neonatal diabetes enables optimization of management strategies, mitigating the long-term impact on growth, neurodevelopment, and the occurrence of hypoglycemic episodes.