Neonatal Diabetes Mellitus Due to Complete Glucokinase Deficiency

Abstract

Diabetes mellitus is a heterogeneous disorder that can occur at any age.¹ 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.² Like diabetes in general, neonatal diabetes is heterogeneous and can be either transient or permanent. Transient neonatal diabetes is associated with abnormalities of chromosome 6,^2,3 whereas mutations in insulin promoter factor 1 result in pancreatic agenesis and permanent neonatal diabetes.⁴ We describe two patients in whom complete deficiency of the glycolytic enzyme glucokinase, a key regulator of glucose metabolism in pancreatic beta cells that couples extracellular glucose to insulin secretion, caused permanent neonatal diabetes.⁵