Neonatal diabetes due to KCNJ11 pathogenic variant and its associated late risks

Neonatal diabetes, characterized by hyperglycemia within the first 6 months of life, is a rare disorder primarily caused by monogenic mutations, exhibiting diverse clinical manifestations. KCNJ11 and ABCC8 pathogenic variants account for most permanent neonatal diabetes cases. We report a case of a 2-day-old presenting with hyperglycemia and later diagnosed with a KCNJ11 pathogenic variant. The male newborn was born in the 35th week of pregnancy. Capillary glucose levels started to rise at the 36th hour of life. A continuous infusion of insulin was started at the 96th hour of life. The need for insulin remained constant. Genetic analysis confirmed a heterozygous pathogenic KCNJ11 gene variant NM_000525.4:c.175G > A p.(Val59Met) via Sanger sequencing (conducted at The Exeter Genomics Laboratory). This variant is associated with neonatal diabetes and a high likelihood of DEND (developmental delay, epilepsy, neonatal diabetes) syndrome. Glibenclamide therapy was started at the age of 57 days. Follow-up visits with the neurology and endocrinology teams showed good glycemic control with glibenclamide, a slight delay in motor development, and no epilepsy. Despite the rarity of genetic neonatal diabetes, it should be considered in infants with persistent hyperglycemia. In some cases, diabetes can be successfully managed with oral sulphonylurea agents, so rapid genetic testing and initiation of appropriate medication are extremely important because they significantly improve quality of life as well as general outcomes.