Neonatal Diabetes Mellitus Due to Complete Glucokinase Deficiency

Abstract

DIABETES mellitus is a heterogeneous disor- der that can occur at any age. Neonatal diabetes mellitus, defined as insulin-requiring hyperglycemia within the first month of life, is a rare disorder that is usually associated with intrauterine growth retardation. Like diabetes in general, neonatal diabetes is heterogeneous and can be either transient or permanent. Transient neonatal diabetes is associ- ated with abnormalities of chromosome 6, whereas mutations in insulin promoter factor 1 result in pan- creatic agenesis and permanent neonatal diabetes. We describe two patients in whom complete deficiency of the glycolytic enzyme glucokinase, a key regulator of glucose metabolism in pancreatic beta cells that cou- ples extracellular glucose to insulin secretion, caused permanent neonatal diabetes.