Persistent hyperinsulinaemic hypoglycaemia in infancy

Abstract

Persistent hyperinsulinaemic hypoglycaemia in infancy (PHHI) is a heterogeneous condition characterised by unregulated insulin secretion in response to a low blood glucose level. It is the most common cause of severe and persistent hypoglycaemia in neonates. It is extremely important to recognise this condition early and institute appropriate management to prevent significant brain injury leading to complications like epilepsy, cerebral palsy and neurological impairment. Histologically, PHHI is divided mainly into three types—diffuse, focal and atypical disease. Fluorine-18-l-3,4-dihydroxyphenylalanine positron emission tomography (18F-DOPA-PET/CT) scan allows differentiation between diffuse and focal diseases. The diffuse form is inherited in an autosomal recessive (or dominant) manner whereas the focal form is sporadic in inheritance and is localised to a small region of the pancreas. The molecular basis of PHHI involves defects in key genes (ABCC8, KCNJ11, GCK, SLC16A1, HADH, UCP2, HNF4A and GLUD1) that regulate insulin secretion. Focal lesions are cured by lesionectomy whereas diffuse disease (unresponsive to medical therapy) will require a near-total pancreatectomy with a risk of developing diabetes mellitus and pancreatic exocrine insufficiency. Open surgery is the traditional approach to pancreatic resection. However, recent advances in laparoscopic surgery have led to laparoscopic near-total pancreatectomy for diffuse lesions and laparoscopic distal pancreatectomy for focal lesions distal to the head of the pancreas.