Neonatal Diabetes Mellitus: An Update on Diagnosis and Management

Abstract

Neonatal diabetes mellitus is likely to be due to an underlying monogenic defect when it occurs at less than 6 months of age. Early recognition and urgent genetic testing are important for predicting the clinical course and raising awareness of possible additional features. Early treatment of sulfonylurea-responsive types of neonatal diabetes may improve neurologic outcomes. It is important to distinguish neonatal diabetes mellitus from other causes of hyperglycemia in newborns. Other causes include infection, stress, inadequate pancreatic insulin production in preterm infants, among others. This review explores the diagnostic approach, mutation types, management, and clinical course of neonatal diabetes.

Keywords: Genetic; Glyburide; Insulin; Monogenic diabetes; Neonatal diabetes.

Figure 1

Mechanisms of overexpression of imprinted genes causing 6q24-related neonatal diabetes. Diabetes in all cases results from overexpression of genes that are normally either silenced by maternal methylation or expressed when paternally inherited. Overexpression thus occurs when A) both copies are paternally inherited in uniparental paternal disomy (UPD6, which can be either complete disomy or heterodisomy), B) an additional copy is paternally inherited due to a duplication that includes 6q24, or C) there is a defect in maternal methylation (which can be due to recessive mutations in ZFP57). Although parent of origin determination or detection of duplication can be possible through a variety of methods, the most comprehensive direct way of testing of overexpression of genes at 6q24 from any cause is methylation-specific multiplex ligation-dependent probe amplification (MS- MLPA) or methylation-specific PCR/sequencing-based and is rarely offered in most commercial laboratories.

Figure 2

Algorithm for considering sulfonylurea trial.