A full-term baby girl born with birth weight of 2.75 kg (10th25th percentile) had an uneventful perinatal course and no history of gestational diabetes. She was admitted to nursery on day 4 for poor feeding. Physical examination was unremarkable. Blood glucose was 0.6 mmol/l upon admission and urine ketone was negative. Electrolytes and blood gas were normal. Glucose infusion rate of 11 mg/kg per min was required to maintain euglycemia. Critical samples revealed insulin of 42 mIU/l while other investigations including cortisol, growth hormone, ammonia and metabolic workup were normal. Diagnosis of hyperinsulinemic hypoglycemia was made. Diazoxide at 5 mg/kg per day was started together with hydrochlorothiazide. It was further titrated up to 7 mg/kg per day and intravenous dextrose could be taken off. Full enteral feeding was later established and she was discharged on day 42 with home blood glucose monitoring. Euglycemia was maintained with the same dose of diazoxide while the child grew. At 3.5 months, blood glucose was high at 11.5 mmol/l. She was admitted for a trial of stopping diazoxide. It was successfully weaned off. At 4.5 years, she was noted to have language delay, rigid and hyperactive behavior. She was assessed in Child Assessment Service, clinical psychology and child psychiatry and diagnosed attention-deficit-hyperactivity-disorder, Aspergers syndrome, specific learning disorder with low average intelligent quotient. She had low mood and anxiety symptoms, and was put on atomoxetine and sertraline. At 17 years, she presented with 2-week history of polyuria and polydipsia. Physical examination was unremarkable. Her body weight was 42.8 kg (3rd10th percentile), body height was 146.5 cm (<3rd percentile), and BMI was 19.9 kg/m2. Blood glucose was 17.1 mmol/l and urine ketone was 4+ at emergency room. Repeated blood glucose was 19.1 mmol/l and blood β-hydroxybutyrate was 0.5 mmol/l at paediatric unit. Blood gas showed no metabolic acidosis. After 2 h of rehydration with normal saline, blood glucose was still high at 16.4 mmol/l and urine ketone was moderate. She was then put on multiple daily insulin injections at 0.8 unit/kg per day. A1c was 13.5%, insulin was 3.8 mIU/l and anti-islet cell antibody was negative. Sanger sequencing revealed heterozygous HNF4A mutation at c.1001_1004dupAGTT p.(Phe335Leufs*12). It was a novel frameshift variant which was absent from normal controls. It was predicted to create a premature stop codon. The girl was switched from insulin to gliclazide and glycemic control was satisfactory with latest A1c of 6.1%.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology