ESPE Abstracts

Introduction: Congenital hyperinsulinism (HI) is the leading cause of persistent hypoglycemia in infants and children. It is a rare glucose metabolism disorder characterized by unregulated secretion of insulin that leads to hyperinsulinemic hypoglycemia (HH). Most cases are caused by mutations in the KATP-channel genes ABCC8 and KCNJ11. KATP-HI can be classified into two distinct histological forms: a diffuse form, in which all of the pancreatic β-cells are affected, and a focal form of localized islet hyperplasia and dysfunction. Differentiating between focal and diffuse HI is of paramount importance as surgical excision of the focal lesion is curative.

Case Report: We present a case report of an infant male, with severe symptomatic hypoglycemia and seizure episode who has a rare ABCC8 gene mutation inherited from his unaffected father and a focal form of HI. These metabolic abnormalities result in a high risk of brain damage and subsequent neurologic sequelae, such as development delays and epilepsy. Infant presented with persistent hypoglycemia shortly after birth. He was admitted to the neonatal intensive care unit where he had repeated episodes of hypoglycemia. Critical specimens confirmed a diagnosis of HI, and treatment was initiated with Diazoxide but without respond to treatment. Then treatment with Octreotid was started and good respond to treatment was observed. Genetic testing revealed a heterozygous paternally inherited ABCC8 missense variant (Chr11:g.17464299). The clinical significance of this variant is currently uncertain. This mutation was inherited from his unaffected father. 18F-DOPA PET-CT scanning was performed and a focal form of HI was diagnosed. PET-CT scan revealed an adenomatous node located in the head of the pancreas. Surgery was performed and a local lesion was removed.

Conclusion: The interest is in the fact that the infant inherited the ABCC8 gene mutation from his unaffected father. The case demonstrates the importance and clinical utility of genetic analyses and PET-CT scanning for informing and guiding treatment and care. Given the presence of a focal lesion this ABCC8 missense variant (Chr11:g.17464299) can be considered as pathogenic. Genetic testing and advanced imaging techniques have allowed for more tailored approaches to treatment, resulting in improved outcomes.

Keywords: ABCC8, Congenital hyperinsulinism, Hypoglycemia, insulin, beta-cell, KATP channel