ESPE Abstracts

Background: Neonatal diabetes mellitus (NDM) is a rare monogenic disorder that typically occurs within the first 6 months of life. However, there is limited information from India about the clinical characteristics, treatment, and long-term outcomes for children with NDM. This study aims to provide a comprehensive overview of one of India's largest cohorts of children with NDM. These children were treated at a single referral center in North India over a span of almost 2 decades.

Objectives: To describe the molecular characterization, clinical phenotype, and follow-up of infants diagnosed with NDM.

Methods: Data collected from children diagnosed with NDM between March 2006 and January 2024 were analyzed. Information on clinical presentation, molecular diagnosis, treatment modalities, and follow-up data were collected from hospital records. Genetic testing was performed using standard protocols, such as Sanger sequencing and next-generation sequencing.

Results: Twenty-nine patients (twenty males) with NDM were identified. The mean age and median birth weight at diagnosis were 15.12 (14.1-36.5) weeks and 2310 (1010-3300) grams, respectively. Out of the total, 22 (75.9%) patients had diabetic ketoacidosis (DKA) at presentation. Genetic testing revealed pathogenic variants in 24 children [KCNJ11 (12/24), INS gene (4/24), EIF2AK3 (3/24), 6q24 (one duplication, one loss of methylation), and one each of LRBA, SLC2A2, and GCK]. Four children (13.7%) had transient NDM, with a mean age of 33.89±30.76 weeks at remission. Transient NDM had less DKA (25% vs 84%) but was noted to have a higher insulin requirement at diagnosis (1.53±1.51 vs 0.97±0.51). An empirical sulfonylurea trial was initiated in 20 babies, and 12 (60%) showed a good response. All these 12 children had mutations in the KCNJ11 or ABCC8 genes and were transitioned from insulin therapy to oral glibenclamide. These children demonstrated outstanding glycemic control without experiencing DKA or symptomatic hypoglycemia. HbA1c levels amongst this cohort was significantly better than other genetic defects [6.46±1.69% vs 9.09±0.93%]. At final follow-up (4.3±3.4 years), the mean HbA1c was noted to be 7.49±2.11%. Two patients, both with EIF2AK3 defects, died during the follow-up period.

Conclusion: This study highlights the genetic heterogeneity of NDM in the Indian population and emphasizes the significance of early genetic testing for personalized management. Empirical sulfonylurea trials proved successful in specific cases, considering that genetic testing was delayed in our resource-limited setting.