1636-P: Transient Neonatal Diabetes: Clinical Differences between Patients Bearing KATP Mutations and 6q24 Defects May Guide Genetic Screening

Abstract Transient neonatal diabetes mellitus (TNDM) is a subtype of neonatal diabetes (diagnosis: ≤ 180 days of life) characterized by remission within months from onset. TNDM is almost invariably associated with mutations in genes encoding the two subunits of ATP-dependent potassium channel (KATP), ABCC8 and KCNJ11, or with defects in chromosome 6. We reviewed genetic data, family history and clinical features including age at diabetes onset, mode of diabetes presentation, birth weight, type of diabetes treatment, time to remission, and diabetes therapy at relapse in 23 patients with TNDM of the Italian collection. Italian data set of TNDM patients included 8 cases with ABCC8 mutation, 8 cases with KCNJ11 mutation and 7 patients with 6q24 defects. Ten patients with KATP/TNDM (62%) had a parent with diabetes or IFG/IGT who carried the mutation. In contrast, none of the parents of patients with 6q24/TNDM showed glucose derangement. Age at diabetes onset did not exceed 5 weeks from birth in patients with 6q24 defects, and ranged from 1 to 34 weeks in patients with KATP mutations. Seven patients with KATP/TNDM presented with diabetic ketoacidosis (DKA); in contrast, three other patients entered into remission without any pharmacological treatment. No patients with 6q24/TNDM had DKA. Age at remission was higher for probands with KATP/TNDM than those with 6q24/TNDM (median 28.5 vs. 8 weeks, respectively, p=0.0023), along with time to remission (20.5 vs. 6 weeks, p=0.0056). Four patients with TNDM who had relapse of diabetes were treated with sulfonylureas (SU), and one with insulin (refusal of SU). Conclusions: TNDM patients with positive family history for diabetes, onset of diabetes beyond 6 weeks from birth and long time to remission should be screened for mutations in KATP genes first. Remission without therapy observed in 3 cases with KATP/TNDM suggests that in parents with diabetes onset in adolescence, mild TNDM could have been overlooked.