Genetic analysis of Italian patients with congenital hyperinsulinism of infancy

Background/Aims: Congenital hyperinsulinism of infancy isa rare disease that needs prompt treatment to avoid braindamage. There are currently no data regarding the clinicaland molecular features of Italian patients. Methods: Thirtythreepatients with HI and their parents were included. Consanguinitywas reported in six patients. Half of patients weremacrosomic at birth. None had raised 3-hydroxybutyrylcarnitineor hyperammonemia. Molecular analysis of ABCC8and KCNJ11 genes was performed in all patients, and subjectswith no mutation underwent analysis of HNF4A andGCK. GLUD1 and HADH genes were analyzed in a patient withleucine sensitivity. Results: Mutations in the ABCC8 andKCNJ11 genes were found in 45% of the patients (6 novel).No mutations in HNF4A, GLUD1 and GCK genes were found.le heterozygous mutation was identified in 24% ofprobands. 72% of the patients were responsive to medicaltreatment, and 44% of the 17 patients with no identified mutationachieved spontaneous remission. Nine children, unresponsiveto medical therapy, underwent pancreatectomy.Conclusion: This is the first report on hyperinsulinism of infancyin Italy, confirming the complexity of the clinical formsand the heterogeneity of the genetic causes of the disease.