ESPE Abstracts

Background: Congenital hyperinsulinism (CHI) is a rare group of genetic disorders resulting in persistent hypoglycemia which can lead to a considerable risk of neurological damage and developmental delay.

Aim: To assess the neurodevelopmental outcome in children with CHI.

Methods: Thirty-three patients with СHI aged from 7 to 58 months were included. All subjects underwent clinical examination including physical and neurological assessment as well as 18F-DOPA PET/CT. Twenty two patients undergone genetic testing (66%). Developmental screening was performed in 6 months after treatment using “Ages and Stages” questionnaires. Such areas as communication, social skills, motor skills (fine and gross), and problem-solving skills were evaluated. Possible risk factors for neurodevelopmental sequelae due to hypoglycemia were analyzed (form, age of onset and confirmation of CHI, lowest recorded blood glucose level, highest rate of glucose consumption). Statistical analysis was performed using Jamovi 2.3.2. Univariate and multivariate binary logistic regression models were applied to determine variables that significantly affected the outcome. A P-value <0.05 was considered statistically significant.

Results: Out of 33 patients 42% (14) had focal form of CHI, 34% (11) had diffuse form and 24% (8) had atypical form of CHI. All patient with focal form undergone surgical treatment and had recovery as a result. Causative variants in KATP-channel were identified in 19 patients (86%). Causative variants in GLUD1 gene were identified in 1 patient, in GCK gene – in two patients. Normal neurodevelopment in general was observed in 23 subjects (69%), 10 patients had developmental delay. Neurodevelopmental outcome in general (P=0,01) and such individual skills as communication (P=0,03), fine (P=0,04) and gross motor (P=0,01), problem solving (P=0,02) in children with a focal form of CHI were significantly better developed than in those with nonfocal forms. Age of onset and confirmation of the disease, the lowest recorded level of glycemia and the highest level of glucose consumption did not significantly affect the formation of either individual skills (with the exception of gross motor skills) or neurodevelopment in general (P>0,05). Gross motor skills in children with a lower level of glucose consumption turned out to be significantly better (P=0.026).

Conclusion: Focal form of CHI has the greatest modifying effect on positive neurodevelopmental outcome. Risk factors associated with disease did not significantly affect the neurodevelopmental outcome other than gross motor skills which were better formed in children with a lower level of glucose consumption.