Background: Congenital hyperinsulinism (CHI) has not been studied in the Ukraine.
Objective and hypotheses: We investigated the genetic aetiology and treatment of patients with CHI.
Method: Routine clinical and laboratory investigations were performed in children with hypoglycaemia. Genetic testing was undertaken for seven patients with CHI from 9 families. KCNJ11, ABCC8, HNF4A genes were sequenced in all patients. For those who were negative in the initial screening, were also tested for GLUD1 gene, as well as tNGS of all known CHI genes was performed. 18F-DOPA PET-CT (and 68Ga-DOTA PET-CT) scans were performed in selected cases.
Results: In seven patients hypoglycaemia (glucose 0,8 [0,5; 1,2] mmol/l) with detectable insulin (43,1 [1,2; 45,9] mIU/l) and/or C-peptide (6,9 [1,1; 9,9] ng/ml) confirmed CHI. The median age at diagnosis was 55,4 [1,0; 330] days and the median birth weight was 4078 [2850; 5200] g. The incidence of CHI in the Ukraine was calculated at 1 in 258,650 births. Mutations were detected in 6/7 patients. In one patient without a mutation, 18F-DOPA and 68Ga-DOTA PET-CT scanning revealed diffuse disease. All patients showed a poor response to medication and had varying degrees of developmental delay and seizures. 5/7 were surgically treated. Postoperative complications included transient fasting hyperglycaemia (1), cicatricial hernia development after convulsions (1) and persistent subclinical exocrine insufficiency (1).
|Patient||Gene||Protein change||Inheritance||Treatment||Histological form|
Conclusion: Children with hypoglycaemia and unsuppressed insulin and C-peptide levels should undergo genetic and eventual PET CT scan for characterization of the type of CHI. Further studies to identify novel CHI genes are required.
Funding information: This work was supported by the Medical Research Council (grant number 98144).
01 - 03 Oct 2015
European Society for Paediatric Endocrinology