CONGENITAL HYPERINSULINISM SECONDARY TO ABCC8 MUTATION

A CASE STUDY

Abstract

INTRODUCTION
Congenital hyperinsulinism (CHI) results in persistent hypoglycaemia beyond infancy. Mutations in the ABCC8 and KCNJ11 genes are the most common aetiologies of congenital hyperinsulinism that leads to inappropriate insulin secretion irrespective of hypoglycaemia.

CASE
A 3-month-old male was referred to the clinic for persistent hypoglycaemia. He was born with a birth weight of 4480 g by elective caesarean section for macrosomia. His mother had an uneventful antenatal period and had a normal OGTT during the pregnancy. Post-delivery, he was initially well until when he developed hypoglycaemia at 28 hours of life. He was transferred to the NICU from the postnatal ward. Hypoglycaemia was persistent requiring high glucose delivery rate up to 10 mg/ kg/min. Glucagon infusion was started and was difficult to wean. Hypoglycaemic hyperinsulinaemia was confirmed at day 21 of life, with concomitant results of insulin 3.4 m IU/L and random blood glucose 1.8 mmol/L. Diazoxide was started. Glucagon infusion was stopped at day 26 of life, and the baby was discharged. He was born from a non-consanguineous marriage. He was the second child in the family. His parents and older sister were well and healthy. There was no known history of neonatal hypoglycaemia nor early-onset diabetes in his family. At 2 years, the patient still required diazoxide with episodes of hypoglycaemia when feeding was delayed. He was referred to the genetic team. Further investigation revealed compound heterozygous mutations at the ABCC8 gene (likely autosomal recessive type) which were c.2992C>T (path); similar to his mother, and another mutation c.4607C>T (VUS). The father did not have any ABCC8 mutations.

CONLUSION
Clinical suspicion of CHI should be highly considered in macrosomic babies with persistent hypoglycaemia in the absence of maternal diabetes. Expedited genetic study should be considered to assist clinical management.