ESPE Abstracts

Backgorund: Neonatal diabetes is a rare genetic condition with multiple mechanisms, some of them diagnosed in molecular levels.

Objectives: To present the incidence, genetics, clinical phenotype and treatment in permanent neonatal diabetes in Kosova.

Methods: Patients with PNDM that were identified between 2007 and 2022 were clinically phenotyped and gene sequencing of ABCC8, KCNJ11 and INS genes were performed initially in all subjects and EIF2AK3, GATA 6, WRS1 genes were sequenced according to clinical phenotype.

Results: 14 cases from 9 non consanguineous families were identified with an incidence of 3.4 in 100.000 live births in Kosova. 11 patients (78%) with autosomal recessive syndrome -Wolcot Rallison Syndrome, 1 patient with de novo heterozygous mutations in GATA6 gene, 1 patient with ABCC8 missense mutation in the SUR1 subunit of the KATP channel and 1 patient with WFS1(Wolfram Syndrome). From 11 cases with WRS, one case with primary Hypothyroidism, one case with cardiac anomalies –ASD (Atrial Septal Defect), 4 patients with skeletal dysplasia, recurrent hepatic failure and growth failure in almost all patients, 3 patients died from hepatic failure. Cardiac defects ASD II and VSD (Ventricular Septal Defect), skeletal dysplasia, Hydronephrosis and absence of gall bladder in case with GATA 6 Haploinsuffiency. Attention deficit with speech delay in case with SUR 1 mutation. Sensor neural deafness, congenital cataracts syndrome and seizures in case with WFS1. All patients were in intensified basal bolus treatment with insulin, case with SUR 1 mutation was safely transferred to sulfonylurea therapy.

Conclusions: In Kosova region with no consanguinity in the families PMND has different genetic etiology, most cases were with rare autosomal recessive syndrome WRS and even more rare diseases can be present as part of isolated country. Early recognition has important implications for appropriate treatment, disease course and associated condition leading to improved outcome.