23-10-2024 | Diazoxide | Case Report
The combination of next generation sequencing and technological devices allows a precision medicine approach in congenital hyperinsulinism: the case of a pregnant mother and the child she gave birth
Authors:
Marina Valenzano, Antonella Peduto, Anna Comba, Claudia Menzaghi, Vincenzo Trischitta
Published in:
Acta Diabetologica
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Excerpt
Congenital hyperinsulinism (CHI) is a heterogeneous disorder defined by severe, recurrent hypoglycaemia (serum glucose level < 60 mg/dl or 3.3 mmol/L) characterized by inappropriate secretion of endogenous insulin, which can be confirmed by measuring serum insulin, C-peptide and pro-insulin levels [
1,
2]. The condition is rare, accounting for 1/30,000–50,000 live births. Two main histological forms of CHI are recognized: focal and diffuse Langherans islet cell hyperplasia [
1,
2].
ABCC8 (encoding the beta-cell high-affinity sulfonylurea receptor, SUR1, a subunit of the K
ATP channel) and
KCNJ11 (encoding the inwardly rectifying potassium channel, Kir6.2) are the genes most commonly involved [
1]. In particular,
ABCC8 loss-of-function mutations can be expressed as recessive forms, responsible for the majority of cases of diffuse and severe CHI, or as dominant forms, responsible for less severe phenotype [
1]. Recessive forms usually do not respond to medical treatment, while dominant
ABCC8 mutations are sensitive to diazoxide [
1], a nondiuretic oral benzothiadiazine. Moreover, several patients with heterozygous
ABCC8 mutations have been reported to present CHI in infancy and then to develop diabetes with age. Patients with CHI are generally macrosomic at birth, hypoglycaemia usually appears in the neonatal period and in half of them manifests with seizures. …