SOMATIC DELETION OF THE IMPRINTED 11P15 REGION IN SPORADIC PERSISTENTHYPERINSULINEMIC HYPOGLYCEMIA OF INFANCY IS SPECIFIC OF FOCAL ADENOMATOUS HYPERPLASIA AND ENDORSES PARTIAL PANCREATECTOMY

Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profoun d hypoglycemia due to inappropriate hypersecretion of insulin. An impo rtant diagnostic goal is to distinguish patients with a focal hyperpla sia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ si gnificantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic v enous sampling coupled with peroperative surgical examination and anal ysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of Fo PHHI, but not those of DiPHHI, there was specific loss of maternal all eles of the imprinted chromosome region 11p15 in cells of the hyperpla stic area of the pancreas bat not in normal pancreatic cells. This som atic event is consistent with a proliferative monoclonal lesion. It in volves disruption of the balance between monoallelic expression of sev eral maternally and paternally expressed genes. Thus, we provide the f irst molecular explanation of the heterogeneity of sporadic forms of P HHI such that it is possible to perform only partial pancreatectomy, l imited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia.