Monogenic Neonatal Diabetes: Clinical Presentations, Genetic Findings, and Response to Therapy in a Retrospective...

Introduction Monogenic neonatal diabetes mellitus (NDM) is a rare form of diabetes, presenting within the first six months of life and caused by pathogenic variants affecting pancreatic β-cell development or function. Because its initial presentation may overlap with type 1 diabetes, molecular diagnosis is crucial, as it directly influences prognosis and treatment - particularly the potential responsiveness to sulfonylureas in ATP-sensitive potassium (KATP)-channel-related NDM. This study reports a retrospective descriptive case series and aims to characterize the clinical and genetic features of infants with NDM, to improve therapeutic management and long-term outcomes. Materials and methods We conducted a retrospective descriptive case series of infants diagnosed with diabetes before six months of age, hospitalized in the Pediatric Endocrinology Unit of the Abderrahim Harouchi Mother-Child Hospital, Casablanca, Morocco, between January 2018 and December 2025. Clinical presentation, biochemical data, insulin requirements, genetic results, and outcomes were extracted from medical records. Genetic testing was performed through next-generation sequencing (NGS), or targeted Sanger sequencing when financially feasible. Results Ten infants were included (nine males and one female), with a mean age at diagnosis of 71 days. Diabetic ketoacidosis (DKA) was the presenting feature in all cases. Consanguinity was reported in 55% of families. Pathogenic or likely pathogenic variants were identified in six infants (60%), involving ABCC8, INS, EIF2AK3, CASP10, and chromosome 6q23-24 duplication, including two syndromic forms. Two infants with ABCC8 mutations achieved insulin independence with sulfonylurea therapy. Syndromic etiologies - Wolcott-Rallison syndrome, Donohue syndrome, and autoimmune lymphoproliferative syndrome type IIA (ALPS-type IIA) - were associated with severe multisystemic involvement. Three children had no identifiable pathogenic variant, despite clinical features consistent with NDM. Long-term outcomes varied widely, ranging from normal neurodevelopment to early mortality in Donohue syndrome. Conclusion This retrospective descriptive case series highlights the marked genetic heterogeneity and clinical variability of neonatal diabetes in a resource-limited setting. Genetic testing enabled precision therapy in infants harboring KATP-channel mutations and clarified prognosis in syndromic forms. Expanding access to molecular diagnostics remains essential to improve equity in care, optimize metabolic outcomes, and support individualized management strategies.