Hyperinsulinism in Infancy (HI) is a potentially-lethal condition of neonates and during early childhood. For many years the pathophysiology of this disorder was unknown. Recent advances in genetics, histopathology and molecule physiology have now revealed the causes of HI in a large cohort of patients. This review focuses upon the relationship between the basis of HI and current treatment options. From defects in ion channel subunit genes to lesions in the control of pancreatic B-cell metabolism and anaplerosis, the causes of HI are both varied and numerous. However, in all cases they appear to share a common target protein – the ATP-sensitive K-channel, whose function is critical to the control of normal insulin-secreting cell function. HI can therefore arise through “channelopathies” of K-ATP channels: HI-KATP through gene defects in ABCC8 and KCNJ11 (Ch11.p15); or as a result of metabolopathies through defects in the genes encoding glucokinase HI-GK (GCK, Ch.7p15-p13), glutamate dehydrogenase HI-GDH (GLUD1, Ch.10q23.3) and Short-chain L-3-hydroxyacyl-CoA dehydrogenase HI-SCHAD (HADHSC, Ch.4q22-q26). Advances in the integration of genetic medicine and cell biology have provided key insights into the causes of HI, and this has been of key importance to the definition of pathogenesis. However, medical therapy for HI remains largely unchanged due to the availability of limited agents that are selective and specific for the termination of insulin release from β-cells.
04 - 06 Apr 2005
British Endocrine Societies