Precision therapy for Developmental delay, Epilepsy and Neonatal Diabetes syndrome in the era of genomics

Abstract

Neonatal diabetes mellitus is a rare disorder with prevalence of one in 400,000 live births that's defined by persistent hyperglycaemia within the first six months of life. Neonatal diabetes is heterogeneous and can be transient or permanent. Developmental delay, Epilepsy and Neonatal Diabetes (DEND) syndrome is characterised by developmental delay, epilepsy, and neonatal diabetes. The most common cause is activating mutations of KCNJ11 or ABCC8 genes, which encode Kir6.2 and SUR1 respectively. KATP channels are expressed in the brain, nerves, muscles, and pancreatic b-cells, implying an association with the neurological features observed in patients. Neonate patients with early onset/neonatal onset diabetes are often misdiagnosed as type 1 DM and do not require lifelong insulin therapy. Whenever associated with neurological features DEND syndrome should be suspected which is a channelopathy affecting pancreas and brain and is amenable to precision therapy. Oral sulfonylureas show promising results in not only attaining euglycemia, but also in controlling seizures and ameliorating developmental delay.

Keywords: Channelopathy; DEND syndrome; Diabetes; Precision therapy; Sulfonylurea.