ESPE Abstracts (2018) 89 P-P3-184

Mutation in UCP2 Gene: A Rare Cause of Hyperinsulinemic Hypoglycaemia Syndrome in a Small-for-Gestational Age Newborn

Maria Clemente, Pamela Yesquen, Ariadna Campos, Eduard Mogas, Mónica Fernández & Diego Yeste


Hospital Universitari Vall d’Hebron, Barcelona, Spain


Hyperinsulinism is a common cause of severe and persistent hypoglycaemia during the neonatal period. Eleven genes have been identified that lead to unregulated insulin secretion and hyperinsulinemic hypoglycaemia (HH). Inactivating mutations in UCP2 gene have been described in a very small number of patients with HH. UCP2 protein is an inner mitochondrial carrier protein and its loss of function causes enhanced glucose oxidation and increased intracellular ATP synthesis leading to HH.

Case report: Male newborn who presented hypoglycaemia since the first hour of life. Family history: no consanguinity. Mother with hypertension. No history of hypoglycaemia nor diabetes mellitus. Obstetric history: First gestation of 34 weeks’ duration. O’Sullivan test and TORCH serologies were normal. Third trimester ultrasound detected intrauterine growth retardation and signs of hemodynamic redistribution. Birth by caesarean section. Apgar 8/9, weight 1630 g (−1.92 S.D.), length 41 cm (−2.23 S.D.) and cephalic perimeter 29 cm (−1.28 S.D.). Physical examination was normal barring an umbilical hernia of less than 1 cm. The patient presented persistent asymptomatic hypoglycaemia that required administration of intravenous glucose boluses and continuous enteral feeding by nasogastric tube thereafter. Carbohydrates were progressively increased up to 17.4 mg/kg per min. There were no clinical-biochemical markers of infection.

Complementary tests: The study conducted during hypoglycaemia (35 mg/dl) revealed detectable insulin level (1.72 mU/ml), slightly high serum ammonium levels (88 mcmol/l, normal value <53), normal cortisol (16 μg/dl), low levels of total free fatty acids (0.18 mmol/l, nv 0.6–1.3), normal ß-Hidroxibutirat (140 μmol/l) and a normal lactate (1.2 mmol/l). Providing the diagnosis of HH. Serum amino acids, urine organic acids profile, acid-base equilibrium, liver and renal functions were normal; echocardiogram and abdominal ultrasound were also normal. Genetic study included ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A, HNF1A, UCP2, HK1 and PGM1 genes; finding an inactivating mutation in UCP2 (c.127-1G>T), a splicing mutation that had not been previously reported.

Evolution and treatment: Diazoxide was started at a dose of 5 mg/kg per day at the age of one month with a positive response. It allowed carbohydrate requirements to be significantly reduced, withdrawing the feeding by gastroclysis and prolonging the interval between takes. Diazoxide was well tolerated and suspended at age of 3 months. Currently the patient tolerates normal fasting time for age.

Conclusion: We have described the case of a small-for-gestational age newborn who presented transitory HH caused by mutation in UCP2 gene that responded to diazoxide treatment.

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