Abstract
Background: The majority of diabetes occurring under 6 months of age is generally thought to be due to a monogenic cause. In neonatal diabetes occurring beyond 6 months, the frequency of autoimmune diabetes increases dramatically. While during this time autoimmune diabetes is more likely, there appears to be continued incidence of monogenic diabetes occurring though the first year of life. For ABCC8, KCNJ11 and INS mutations, though the majority of cases occur prior to 6 months of age, cases have been reported past 6 months of age through 12 months of age and beyond; as such, testing through 13 months can provide valuable information to physicians and families. Methods: Participants were enrolled in the University of Chicago Monogenic Diabetes Registry. Genetic testing was performed for participants without a known monogenic form of diabetes, including either 1) Sanger sequencing for KCNJ11, ABCC8, and INS or 2) next-generation sequencing panel covering all known forms of neonatal diabetes. Data were stored using REDCap. Results: One hundred ninety participants who were diagnosed between 6-13 months of age were identified. Of these, 118 have had extensive genetic testing completed and thus will be the focus of this abstract. Fifty participants were diagnosed between 6-8.9 months (mean age 7.3 months, 54% male, 72% Caucasian) and 68 cases between 9-13 months (mean age 10.78 months, 72% male, 81% Caucasian). Of 50 patients enrolled in the registry between age 6-8.9 months, 44% were found to have a monogenic cause (n =22). INS mutations were the most common cause (n=8, 36%), followed by KCNJ11 (n=5, 23%), ABCC8 (n=4, 18%), FOXP3 (n=3, 14%), and GATA4 (n=2, 9%). Of this group, 16 patients had reported antibody testing, with 4 (25%) having positive antibodies. T1D risk scores were below the 50th percentile for 49% of those tested. For 68 patients diagnosed between 9-13 months, 18% had a monogenic cause (n = 12). INS mutations were the most common cause (n=5, 42%), followed by GCK (n=4, 33%), ABCC8 (n=1, 8%), KCNJ11 (n=1, 8%), and HNF4A (n=1, 8%). Antibody testing was reported in 9 participants, of whom 3 were positive (33%). Conclusion: Though most neonatal diabetes above 6 months of age can be attributed to autoimmune diabetes, monogenic diabetes continues to occur. In examining our cohort of patients diagnosed with diabetes between 6-13 months, a substantial number have a genetic cause of diabetes (6-8.9 months 44%, 9-13 months 18%). Though more data is needed, genetic testing beyond 6 months through age 13 months continues to provide valuable clinical information.