Objective: Congenital hyperinsulinism (CHI) is the most common cause of hypoglycaemia in children. Early identification and management is crucial to prevent irreversible brain damage. CHI has a heterogeneous clinical presentation, histology and molecular biology. We aim to discuss the clinical characteristics and genotypephenotype correlations of Turkish CHI patients from a single centre.
Design and methods: A total of 15 patients with CHI were recruited from one paediatric endocrine centre in Turkey. Patients with secondary hyperinsulinaemic hypoglycaemia (HH) due to IUGR, perinatal asphyxia, or maternal diabetes mellitus were excluded. All patients had normal acylcarnitine and urine organic acid profile. ABCC8 and KCNJ11 were sequenced in all patients and if no mutations were identified HADH sequencing was performed.
Results: A genetic diagnosis was made in 9 (60%) patients (HADH n=5, ABCC8 n=2, and KCNJ11 n=2). Diazoxide unresponsiveness was observed in one patient with a KCNJ11 mutation who was managed with subtotal pancreatectomy. Among the diazoxide-responsive patients (n=14), mutations were identified in eight cases (57%). Genotypephenotype studies showed that ABCC8 and KCNJ11 mutations resulted in increased birth weight and HADH mutations were associated with liver dysfunction progressing from mild to severe disease. The clinical, biochemical and genetic characteristics of patients are summarised in Table 1.
Conclusions: Our results are different from previous studies from Turkey which report recessive ABCC8 and KCNJ11 mutations as the most common cause of CHI. We identified mutations in three different genes in 57% of diazoxide-responsive patients which is a higher pick-up rate compared to other studies. Homozygous HADH mutations are a rare cause of CHI but in our cohort they accounted for 33% of cases. Hepatic dysfunction, cardiomyopathy or effects on skeletal muscle have not been reported in patients with HADH mutations to date. This work therefore extends the phenotype associated with these mutations.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology