Endocrine Abstracts

JOINT3444

Introduction: Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes that presets within the first six months of life, and is classified as either transient (TNDM) or permanent (PNDM). This study aims to describe the clinical characteristics, genetic findings, treatment strategies, and long-term follow-up of 11 NDM patients based on a single-center experience.

Methods: This study involved 11 patients with NDM diagnosed, treated, and followed between 2013 and 2025 years. Clinical, biochemical, and genetic data were evaluated retrospectively. Genetic analysis was performed in all patients.

Results: Among 11 patients (7 male) from 9 unrelated families, TNDM and PNDM were diagnosed in 1 and 10 patients. Sixty-four percent were born to consanguineous parents. Genetic mutations were identified in 64%, the most common mutation was in the PTF1A distal enhancer (n = 6)), one patient had KCNJ11 mutation. Fifty-four percent were born prematurely, and 90. 9% were small for gestational age. The median age at diagnosis was 1 day, All patients received insulin replacement therapy. Glibenclamide was initiated in the patient with the KCNJ11 mutation. In PNDM patients, the median insulin dose was 0. 55 U/kg/day initially and 0. 58 U/kg/day at last follow-up, with no significant difference. Six patients received insulin via insulin pumps. Median HbA1c at last control was 7. 5% and there was no difference in HbA1c levels compared to conventional insulin treatment. Patients with PTF1A mutations diabetes was associated with pancreas agenesis, thus they required pancreatic enzyme replacement. Pancreas agenesis was not associated with other abnormalites. One patient whose genetic analysis is pending has also exocrine pancreas insufficiency whose pancreas could not be visualized. All males exhibited catch-up growth, surpassing -2 SDS; whereas two females under two years remained below -2 SDS. These females with height below -2 SDS also had low weight. Except for the deceased KCNJ11-positive patient, all males achieved weight above -2 SDS at last follow-up.

Conclusion: NDM is a rare disorder with variable genotypes and clinical phenotypes. PTF1A mutation was the most common genetic cause in our cohort, particularly relevant in populations with high consanguinity rates. Genetic testing is crucial for identifying conditions such as pancreatic agenesis and initiating timely treatment, as well as guiding appropriate treatments such as sulfonylurea therapy in KCNJ11 mutations.