Background: Hyperinsulinaemic hypoglycaemia (HH) is a clinically and genetically heterogeneous group of disorders characterized by persistent hypoglycaemia due to inappropriate insulin secretion from the pancreatic β-cell.
Aim: The objective was to analyze the demographic, clinical and genetic characteristics of patients with HH, diagnosed and/or treated at a tertiary endocrine center, part of the European reference network on rare endocrine conditions (ENDO-ERN).
Material and Methods: The medical records of a total of 13 patients with congenital HH (9 persistent, 3 transient, and 1 syndromic cases) were retrospectively reviewed. Data about their demographic, clinical and biochemical characteristics were collected. Genetic testing was performed in all patients with persistent and syndromic hyperinsulinism.
Results: Ten children (76.7%) were males and almost 2/3 of the patients (61.5%) presented at birth with hyperinsulinism. Four patients (30.8%) were born large for gestational age and the most common clinical manifestations at presentation were neuroglycopenic symptoms. ABCC8 and GLUD1 gene mutations were identified in 44.4% of the nine children with persistent hyperinsulinism. Of the three ABCC8 cases, one had homozygous p.(Gly92Asp) mutation, one was compound heterozygous p.(I60N)/p.(G1555V) and one was heterozygous for a dominant mutation p.(E1507K). The patient with syndromic hyperinsulinism was diagnosed with Beckwith-Wiedemann syndrome due to a loss of heterozygosity for the maternal allele resulting in loss of methylation in KvDMR and gain of methylation in H19 DMR. Eleven children (84.6%) were diazoxide responsive and two patients received octreotide treatment. Patients with detected mutations were diagnosed earlier, with lower blood glucose levels and required higher doses of diazoxide compared to children without a genetic diagnosis. More than 92% (12/13) of the children with HH had normal neurological development, excluding one patient with expressive language problems due to diagnostic and treatment delay.
Conclusion: The majority of hyperinsulinaemic patients have no identifiable mutations, suggesting the role of other genetic and environmental mechanisms. Since most of the patients present soon after birth, early recognition and prompt treatment are vital in preventing permanent brain damage.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology