Diazoxide-unresponsive Hyperinsulinemic Hypoglycaemia in a Preterm Infant with Heterozygous Insulin Receptor Gene Mutation

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What is already known on this topic ?Homozygous or compound heterozygous mutations in INSR gene cause severe insulin resistance syndromes Donohue syndrome (DS, also known as leprechaunism) and Rabson-Mendenhall syndrome (RMS) whereas heterozygous INSR gene mutations result in a milder phenotype known as type A insulin resistance syndrome (type A-IR).Adults with type A-IR commonly demonstrate abnormal glucose homeostasis with fasting and postload hyperglycaemia, as well as high testosterone levels compared to age-matched controls.Phenotypes and clinical course in children, especially infants, with heterozygous INSR gene mutations are less reported.There is also lack of literature on how these infants can be managed. What this study adds?We report a preterm infant who presented with diazoxide-unresponsive hyperinsulinemic hypoglycaemia.Whole-exome sequencing revealed heterozygous INSR gene mutation in the infant and her father.We postulated that use of diazoxide exacerbated post-prandial glucose excursion by inhibiting insulin release, while hypoglycaemia that follows could be explained by reduced degradation or clearance of insulin due to the underlying mutation.Our study highlights that in situation where mutations could not be identified by targeted sequencing of ABCC8/KCNJ11 or GCK genes in an infant with suboptimal response to diazoxide, sequencing of the INSR gene should be considered.Indeed, INSR gene should be included in the targeted gene panel for workup of hyperinsulinism.

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