Endocrine Abstracts

Introduction: Congenital Hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in neonates, infants and children with an incidence of 1/25000-1/50000 live births. HNF4A and HNF1A mutations lead to maturity onset diabetes of the young (MODY 1 and 3 respectively) with a potential for causing CHI in the newborn period. Whilst HNF4A mutations causing CHI is well known, reports on CHI due to HNF1A mutations are very limited.

Case report: A baby boy was born by emergency caesarean section for foetal distress with a birth weight of 4.26 kg (+1.65SD). The mother had gestational diabetes mellitus managed on diet. He suffered a caecal perforation on day 3 of life and underwent right hemicolectomy with colostomy. His echocardiogram demonstrated persistent duct arteriosus and left ventricular hypertrophy. He developed persistent hypoglycaemia on day 2 of life and the hypoglycaemia screening (blood glucose: 2 mmol/l, insulin: 406 pmol/l, c-peptide: 2095 pmol/l, 3-hydroxy butyrate: 87 umol/l, free fatty acid: 143 umol/l and cortisol: 659 nmol/l) confirmed CHI. He was initially managed with high concentration dextrose fluids [GIR: 21.5 mg/kg per min] and glucagon [10 μg/kg per hour] and subsequently he was commenced on diazoxide (3 mg/kg/day) and chlorothiazide (7 mg/kg per day) to which he responded well. The dose of diazoxide had to be gradually increased over the first year of his life to establish euglycaemia [up to 10 mg/kg per day]. His mother was subsequently diagnosed with Type 2 Diabetes Mellitus requiring metformin. The genetic analysis identified a novel heterozygous variant in HNF1A [c.713G>T p.(Arg238Met)], which was maternally inherited (consistent with MODY 3 clinical phenotype in mother).

Conclusion: We present a rare cause of diazoxide-responsive CHI due to a novel HNF1A mutation which has also caused MODY 3 in mother. Infants and children with transient, diazoxide-responsive CHI might merit from screening for HNF4A and HNF1A mutations, especially in the presence of family history of diabetes mellitus, to predict the long term risk of MODY in adulthood.