J Clin Res Pediatr En docrinol 2012;4(4):169-181 DO I: 10.4274/Jcrpe.821

In tro duc ti on Hyperinsulinaemic hypoglycaemia (HH) represents a group of clinically, genetically, and morphologically heterogeneous disorders characterized by dysregulation of insulin secretion by pancreatic β-cells (1). It is the commonest cause of both transient and persistent states of hypoglycaemia posing significant risk of permanent brain damage (2,3,4). Insulin secretion from β-cells is precisely regulated by various mechanisms to maintain blood glucose values within the normal range (fasting blood glucose levels of 3.5–5.5 mmol/L). HH-unregulated insulin secretion drives glucose into insulin-sensitive tissues (skeletal muscle, liver and adipose tissue) and prevents the generation of alternative energy substrates (such as lactate and ketone bodies due to inhibition of glycogenolysis, gluconeogenesis, lipolysis and ketogenesis) thereby depriving the brain of glucose and ketone bodies. It is this metabolic milieu that results in hypoglycaemic brain injury (2). Clinically, HH can result in apneas, seizures, developmental delay, and learning disability (4). Hence, early identification and meticulous management of these patients is fundamental in preventing a neurological insult. HH can either be congenital hyperinsulinism (CHI) or secondary to certain risk factors like birth asphyxia, intra-uterine growth retardation (5), Rh isoimmunisation (6) and maternal diabetes mellitus or associated with various developmental syndromes like Beckwith-Wiedemann syndrome or metabolic conditions like congenital disorders of glycosylation (CDG syndromes) (7). In adults, an insulinoma accounts for most cases of HH. Other causes include noninsulinoma pancreatogenous hypoglycaemi