Incidence, Phenotypes, and Genotypes of Neonatal Diabetes: A 16-Year Experience. The Rare Genetic Etiologies of Neonatal Diabetes Are Common in Sudan

Abstract

Neonatal diabetes (ND) is a rare subtype of diabetes occurring in the first 6 months of life. High incidence has been reported among populations with high rates of consanguineous marriage. However, there is paucity of reported data from sub-Saharan African countries. We report the incidence, genotype, and phenotype of ND in a large cohort from Sudan and compare these findings to regional and international data. All infants with onset of diabetes in the first 6 months of life, attending one of the only two tertiary pediatric diabetes centers in Sudan, Gaafar Ibn Auf Pediatric Tertiary Hospital and Sudan Childhood Diabetes Center, during the period of January 2006 to December 2022 were included. Medical records were reviewed for demographic and clinical information. Genetic testing was performed for 48 patients by the Exeter Genomics laboratory in the UK and for one patient by the University of Cambridge, Metabolic Research Laboratories, UK. The estimated incidence was 4.8 per 100,000 live births. Forty-nine ND patients from 45 unrelated families were identified, and a genetic diagnosis was confirmed in 37 patients (75.5%) from 33 unrelated families. Consanguinity was reported in 34 families (75.6%). The commonest genetic cause for permanent neonatal diabetes was <i>EIF2AK3</i> recessive variants causing Wolcott-Rallison syndrome (18.92%). Pathogenic variants in two recently identified genes, <i>ZNF808</i> and <i>NARS2</i>, were found in three patients each (8.11%). Activating variants in <i>KCNJ11</i> and <i>ABCC8</i> were identified in four (10.81%) and two (5.41%) patients, respectively. Apart from hyperglycemia, the commonest clinical presentations included dehydration, failure to thrive, and diabetic ketoacidosis. ND in Sudan has a different pattern of etiologies compared to Western and Asian populations yet similar to some Arab countries with <i>EIF2AK3</i> mutations being the commonest cause. Pathogenic variants in recently identified genes reflect the impact of genome sequencing on increasing the rate of genetic diagnosis.