AB076. Congenital hyperinsulinism due to mutation of HNF4A: a case report

Background: Hyperinsulinemic hypoglycemia (HH) is the commonest cause of persistent hypoglycemia in the neonatal and infancy periods. HNF4A mutations are the third most common cause of diazoxide responsive congenital hyperinsulinism. Individuals carrying HNF4A mutations that result in familial monogenic diabetes later in life can present in early infancy with hyperinsulinism. The study was to describe a child associated with HH due to mutations in the HNF4A gene.

Methods: Clinical data were obtained from chart review. Gene sequencing of HNF4A was performed.

Results: At the National Hospital of Pediatric from January 2007 to April 2015. We have 68 cases with congenital hyperinsulinism diagnosed and molecular analysis. Mutation HNF4A gene found 1/68 cases (1.47%). A boy born large for gestational age (birth weight 4,700 g with 40 gestation weeks) after an uneventful pregnancy, presented 24 h after birth with lethargy, poor feeding, cyanosis, no seizure caused by severe hypoglycaemia (serum glucose 0.5 mmol/L). Hypoglycaemia was treated with 2 mL/kg 10% glucose i.v. followed by a continuous i.v. glucose infusion (9.57 mg/kg/min) to maintain serum glucose above 3 mmol/L. Laboratory investigations at the time of hypoglycaemia showed inadequate suppression insulinemia (57.9 pmol/L) and C-peptide (0.38 nmol/L), negative ketone bodies, absent urine ketone bodies, hyperammonemia (365.1 µg/dL), hypofattyacidaemic. His mother had three pregnancies [the first boy born with 35 gestational weeks (birth weight 2,800 g), died 2 days after birth with cyanosis unknown causes, the second 28 gestational weeks boy, died some hours after birth with cyanosis unknown causes]. A diagnosis of ‘hyperinsulinism’ was made. Molecular analysis showed he is heterozygous for a novel HNF4A missense mutation on location Exon 6, protein description p.Leu220Pro (p.L220P) from his mother. The leucine residue at codon 220 is highly conserved across species and it is therefore likely, although not certain, that the p.L220P mutation is pathogenic. Treatment was started with diazoxide (10 mg/kg per day in three doses) and had good response and stopped diazoxide after 2 weeks with normal glucose level and normal. Up to now, he is 5 years old with normal growth and development, normal glucose level.

Conclusions: Babies who inherit the HNF4A gene often have a high birth weight (over 4 kg) and may have low blood sugars early in life (neonatal hypoglycaemia) needing treatment immediately after birth. HNF4A mutations responses well to diazoxide.

Keywords: Hyperinsulinism; HNF4A