Congenital Hyperinsulinism Due to a Novel Activating Glucokinase Mutation: A Case Report and Literature Review

Abstract

Nikitas S Skarakis, Christina Kanaka-Gantenbein, Dimitra Dimopoulou, Amalia Sertedaki and Feneli Karachaliou

Background: Congenital Hyperinsulinism (CHI) constitutes a major cause of persistent and recurrent hypoglycemia, especially in the neonatal period, showing notable phenotypical heterogeneity among affected subjects. Activating mutations of the Glucokinase gene (GCK) are responsible for mild forms of hypoglycemia, due to CHI, usually easily medically managed.

Case report: We present a patient at the age of 3.5 years old investigated for persistent hypoglycemia. Laboratory evaluation showed hyperinsulinism during the hypoglycemic episode with a required glucose infusion rate greater than 8-10 mg/kg/min to maintain normoglycemia. Targeted gene panel sequencing revealed an activating missense novel mutation p.Val71Ala in exon 3 of GCK gene, dominantly inherited by his mother. In silico, analysis of this novel missense variant assessed its pathogenicity as being of uncertain significance.

Conclusions: GCK gene mutations result in varying phenotypic characteristics and responsiveness to diazoxide depending on the type of activating mutation.

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