RT Journal Article
T1 Clinical and genetic characterization of congenital hyperinsulinism in Spain
A1 Martinez, R.
A1 Fernandez-Ramos, C.
A1 Vela, A.
A1 Velayos, T.
A1 Aguayo, A.
A1 Urrutia, I.
A1 Rica, I.
A1 Castano, L.
A1 Spanish Congenital Hyperinsulinism, 
K1 Heterozygous abcc8 mutation
K1 Sulfonylurea receptor sur1
K1 Atp channel mutations
K1 Molecular characterization
K1 Glutamate-dehydrogenase
K1 Hyperammonemia syndrome
K1 Phenotype correlations
K1 Glucokinase mutation
K1 Dominant mutations
K1 Diabetes-mellitus
AB Context: Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disease characterized by severe hypoglycemia caused by inappropriate insulin secretion by pancreatic beta-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.
PB Bioscientifica ltd
SN 0804-4643
YR 2016
FD 2016-06-01
LK https://hdl.handle.net/10668/25607
UL https://hdl.handle.net/10668/25607
LA en
DS RISalud
RD Apr 3, 2025