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Purpose: In patients diagnosed with diabetes mellitus (DM) before the age of 12 months, there is an increasing recognition of diabetes caused by single-gene mutations, also known as monogenic diabetes of infancy or neonatal DM (NDM). This study aimed to classify patients at Alexandria University Children's Hospital (AUCH) diagnosed with infantile-onset DM into type 1 DM (T1DM) or NDM and to detect differences in molecular characteristics of NDM patients at our center in comparison to other countries. Methods: This retrospective/prospective observational study was conducted on 39 patients diagnosed with infantile-onset DM (age of onset =1 year) at AUCH from January 2003 to November 2020. The patients were divided into 2 groups according to age at the onset of DM: =6 months and >6-12 months. Molecular testing was done in patients diagnosed with DM at =6 months and those with negative autoantibodies. Results: Twelve patients were diagnosed with DM at age =6 months and 27 patients were diagnosed between 6-12 months. Seventeen patients (43.6%) had T1DM, whereas 9 patients (23.1%) had genetically confirmed NDM, including 3 harboring novel mutations. The most common genetic causes of NDM were EIF2AK3 mutations (n=3), followed by KCNJ11 (n=2) and ABCC8 (n=2). Other mutations included SLC19A2 (n=1) and INS (n=1). Three patients with potassium ATP channel mutations were transferred from insulin to sulfonylurea treatment. Conclusion: It is essential to identify patients with NDM clinically and confirm the diagnosis by molecular testing to distinguish them from T1DM as it helps in refining their management, predicting prognosis, and guiding genetic counseling. [ABSTRACT FROM AUTHOR]

Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes resulting from mutations in more than 20 different genes encoding proteins playing a key role in the normal function of the pancreatic beta-cell. Mutations in the genes encoding the ATP-sensitive potassium channel, ABCC8, and KCNJ11 and insulin (INS) gene are the most common causes of NDM; however, in consanguineous populations, EIF2AK3 mutations are more common. Identification of the causative mutations by genetic testing is critical for appropriate management and to guide genetic counseling. To determine the genetic etiology of NDM in diabetic neonates and infants diagnosed before the age of 1 year and to describe their phenotype/genotype characteristics, DNA sequencing of coding regions and intronic boundaries of ABCC8, KCNJ11, INS, and EIF2AK3 genes was undertaken in 20 patients. Further, targeted next-generation sequencing was performed for other genes known to cause NDM. ABCC8 mutations were found in two patients (10%), with compound heterozygous mutations (p.N131 K/p.R598*) in one patient and a homozygous mutation (p.R1554Q) in the another patient. Heterozygous p.A174G and p.V59M mutations of KCNJ11 were identified in two patients (10%), and homozygous EIF2AK3 mutations were identified in two further patients (p.T905fs and p.R653T) (10%). No INS mutations were identified. Further testing identified a SLC19A2 mutation (p.W387*) in one patient (5%) and the same homozygous GCK mutation in two siblings (p.A188T). ABCC8, KCNJ11, and EIF2AK3 mutations were the main genetic causes of permanent NDM among Egyptian neonates. [ABSTRACT FROM AUTHOR]