Focal Hyperinsulinism Due to 2 Novel Paternally Derived Mutations in SUR1 and Kir 6.2

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is heterogeneous condition often due to focal adenomatous hyperplasia of the pancreas. Secretion of insulin is unregulated, resulting in profound hypoglycemia. Mutations in the genes of both subunits of the betacell KATP channel, Kir6.2 (potassium channel) and SUR1 (sulfonylurea receptor) have been associated with the autosomal recessive form of this disorder. Patients harboring SUR1 mutations often do not respond well to diazoxide (D). Generally in focal forms two paternal alleles are present with subsequent alteration of insulin secretion. The lesions can be cured by selective resection, but these lesions are difficult to detect. The definitive diagnostic tool are pancreatic venous sampling (PVS) and 18Fluoro L-DOPA>positron emission tomography (PET-DOPA). Patient was born at term (BW 4.1 kg), soon after birth he developed hypoglycemia occasionally symptomatic with tremors and hypotonia, required increased glucose therapy (9mg/kg/min, i.v.) despite milk administration (75cc/kg/day). No response to glucagon (0.5mg/kgday i.v.) and D (20mg/kg/day, per os). Good response to octreotide injections (32.2 microgr/kg/day, s.c.). Pancreatic biopsy, genetic study and PET<ndash>DOPA were performed. Pancreatic biopsy on our patient shows normal <beta><ndash>cell nuclei, no evidence of diffuse disease. Genetics demonstrated he has 2 paternally derived mutations in SUR1 and Kir 6.2, causing abnormal insulin secretion (which type of mutation?). The whole body examination with PET<ndash>DOPA scan demonstrated a very intensive focus in the uppermost area of the corpus of the pancreas.In our patient, as suspected by no response to D, SUR1 mutation was demonstrated. Moreover, like our child, we suggest that all patients with PHHI D resistant should have PET-DOPA that represents a noninvasive method for the identification and localisation of focal PHHI. Focal forms of PHHI should be operated because complete cure without risk of diabetes.