Purpose of review
Here we give context to new data on neonatal diabetes mellitus, a rare group of insulin-requiring monogenic forms of diabetes presenting at birth or shortly thereafter. Genetic studies are critical in the diagnosis and treatment of these patients. The most common causes of neonatal diabetes are activating mutations in the two protein subunits of the ATP-sensitive potassium channel. These are responsible for about half of all cases of permanent neonatal diabetes and some cases of transient neonatal diabetes. Identification of these mutations allows patients treated with insulin to be transferred to sulfonylureas, but associated conditions and other causes must be considered.
Recent data suggest that neonatal diabetes is more common than previously thought, with variable presentations. Continued studies provide further evidence for amelioration of developmental and neurological dysfunction exhibited by a significant proportion of patients. Abnormalities of chromosome 6q24 remain the most common cause of transient neonatal diabetes. Other causes of neonatal diabetes being studied include mutations in proinsulin, FOXP3 mutations in immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, homozygous glucokinase mutations, and Wolcott–Rallinson/EIF2AK3 diabetes.
We still have much to learn about the different forms of neonatal diabetes, their associated clinical features, and the optimization of therapy using a growing number of available therapeutic agents.