ESPE Abstracts

Introduction: Congenital hyperinsulinism (CHI) is a rare disease characterized by excessive and inadequate insulin secretion from the pancreatic beta cells. Age at first symptoms and severity are usually correlated with the molecular mechanism, late diagnosis or even misdiagnosis are frequently seen. A genetic cause can be identified in only 50% of cases, potassium channel mutations are the most common mutations causing severe forms. Glucokinase mutation (GCK) being one of the rarest causes of hyperinsulinemic hypoglycemia.

Case report: We report the case of a 10-year-old boy. He is the third child of non-consanguineous parents with a rich family history of diabetes. He was born at 32 weeks of gestation. His birth weight was 2400 g (95^th percentile), head circumference 31 cm, and length 47,5 cm (95th percentile). His neonatal period was marked by respiratory distress and one episode of hypoglycemia. At the age of four, he presented with a generalized hypoglycemic seizure. On examination: weight of 43 kg (+1,80 SD), length of 137,5 cm (-0,45 SD) and BMI of 23,8 kg/m² (+2,58 SD). No dysmorphic features or organomegaly or hepatomegaly were remarked. Critical sample performed on hypoglycemic state of 0.46 g/l (2,54 mmol/l) revealed high insulinemia: 15.3 µU/ml and C-peptide 2.17 ng/ml without cetonuria confirming the diagnosis of HI. Abdominal MRI and 18F-DOPA PET/CT scan were both normal. Genetic testing, revealed a new GCK intronic variant on Ch7: 444192891del (c.208+9). Patient was diazoxide responsive at very low dose, treatment could be discontinued few years later with good glycemic control. We otherwise observed a clear increase in his BMI.

Discussion: We present a novel « de novo » gain-of-function variant of GCK gene mutation in a patient with congenital hyperinsulinism. To the best of our knowledge, this mutation has never been described in literature. The course of hyperinsulinism related to the GCK mutation might vary from a mild form of hypoglycemia, which can be managed with diazoxide to a severe form. Our patient was asymptomatic until the age of 4 years, and was successfully treated with Diazoxide. This case shows the possible favorable course of the disease over time, long term follow is needed.

Conclusion: Despite the underlying molecular mechanism, some forms of CHI may remain poorly symptomatic till early childhood. Our case illustrates well the importance of GCK gene analysis even in older children.