Hotspot mutations such as T1042Qfs*75, I1511K, E501K, G111R in ABCC8 gene, and R34H in KCNJ11 gene are predominantly responsible for Chinese CHI patients.
Pathogenic variants in GLUD1 typically present in late infancy, are diet and/or diazoxide-responsive and cause protein-induced hyperinsulinemic hypoglycemia as insulin secretion is triggered by allosteric activation of GDH by leucine.
Pathogenic variants in at least twelve different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A, HNF1A, UCP2, TRMT10A HK1, and PGM1) are known to cause CHI.
We have identified two novel GCK-CHI mutations in young patients and investigated their pathogenicity by enzyme kinetic analysis, which expanded the spectrum of this rare disease.
These patients emphasize that NSD1 haploinsufficiency is sufficient to cause HI, and suggest that Sotos syndrome should be considered in patients presenting with neonatal HI.
Our results suggest that ATP binding to SUR1 biases K<sub>ATP</sub> channels toward open states, consistent with SUR1 variants with lower <i>K<sub>D</sub></i> values causing neonatal diabetes, whereas increased <i>K<sub>D</sub></i> values cause congenital hyperinsulinism.
Glucagon-like peptide 1 (GLP-1) drives postprandial hyperinsulinemic hypoglycemia in pregnant women with a history of Roux-en-Y gastric bypass operation.
Case 1: A 1-month-old boy diagnosed with diazoxide-unresponsive CHI due to a paternal heterozygous ABCC8 gene mutation showed partial response to octreotide.
A long-acting somatostatin analogue (lanreotide) is used in the management of a diazoxide-unresponsive diffuse form of congenital hyperinsulinism (CHI).
These findings support the potential use of insulin receptor antagonists as a therapeutic approach to control the hypoglycemia in congenital hyperinsulinism.
Thus, these studies demonstrate a critical role for PHPT-1 in normal pancreatic β-cell function and raise the possibility that mutations in PHPT-1 and/or TRPC4 may account for yet to be defined cases of CHI.
<i>PHPT-1<sup>-/-</sup></i> mice exhibited neonatal hyperinsulinemic hypoglycemia due to impaired trafficking of K<sub>ATP</sub> channels to the plasma membrane in pancreatic β-cells in response to low glucose and leptin and resembled patients with congenital hyperinsulinism (CHI).
We report a mutation in FOXA2 leading to congenital hyperinsulinism and hypopituitarism and provide functional evidence of the molecular mechanism responsible for this phenotype.
We report a mutation in FOXA2 leading to congenital hyperinsulinism and hypopituitarism and provide functional evidence of the molecular mechanism responsible for this phenotype.