RESUMO
CONTEXT: Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disease characterized by severe hypoglycemia caused by inappropriate insulin secretion by pancreatic ß-cells. OBJECTIVE: To characterize clinically and genetically CHI patients in Spain. DESIGN AND METHODS: We included 50 patients with CHI from Spain. Clinical information was provided by the referring clinicians. Mutational analysis was carried out for KCNJ11, ABCC8, and GCK genes. The GLUD1, HNF4A, HNF1A, UCP2, and HADH genes were sequenced depending on the clinical phenotype. RESULTS: We identified the genetic etiology in 28 of the 50 CHI patients tested: 21 had a mutation in KATP channel genes (42%), three in GLUD1 (6%), and four in GCK (8%). Most mutations were found in ABCC8 (20/50). Half of these patients (10/20) were homozygous or compound heterozygous, with nine being unresponsive to diazoxide treatment. The other half had heterozygous mutations in ABCC8, six of them being unresponsive to diazoxide treatment and four being responsive to diazoxide treatment. We identified 22 different mutations in the KATP channel genes, of which ten were novel. Notably, patients with ABCC8 mutations were diagnosed earlier, with lower blood glucose levels and required higher doses of diazoxide than those without a genetic diagnosis. CONCLUSIONS: Genetic analysis revealed mutations in 56% of the CHI patients. ABCC8 mutations are the most frequent cause of CHI in Spain. We found ten novel mutations in the KATP channel genes. The genetic diagnosis is more likely to be achieved in patients with onset within the first week of life and in those who fail to respond to diazoxide treatment.