Impact of Timing of Initiation of Sulphonylurea Therapy on Neurodevelopmental Outcomes in Individuals With Intermediate Developmental Delay, Epilepsy and Neonatal Diabetes (iDEND) Syndrome Due to the V59M Mutation in the KCNJ11 Gene
Royal Devon and Exeter NHS Foundation Trust
Summary
The goal of this observational study is to learn about the impact of the diabetes drug glibenclamide (glyburide) on neurodevelopment in individuals with iDEND (developmental delay, epilepsy and neonatal diabetes) due to the V59M mutation in the KCNJ11 gene. The main question it aims to answer is whether initiating sulphonylurea (SU) therapy in the first year of life results in better neurodevelopmental outcomes in affected individuals, in comparison to starting therapy later than 12 months of age. Participants will undergo a neurodevelopmental assessment comprising parental and teacher completion of standardised questionnaires, and where possible face to face neuropsychological testing. Researchers will compare the outcomes of these standardised tests in the individuals who started SU therapy \<12 months of age in comparison to those who started \>12 months of age.
Description
Background: The role of the KATP channel in the pancreas The KATP channel is made up of 4 pore-forming Kir6.2 subunits (encoded by the KCNJ11 gene) and 4 regulatory SUR1 subunits (encoded by the ABCC8 gene). In the pancreas, the KATP channel plays a central role in glucose-stimulated insulin secretion. KATP channel mutations cause neonatal diabetes that can be treated with oral sulphonylureas Neonatal diabetes is defined as diabetes occurring in the first 6 months of life; it has an incidence of approximately 1 in 200,000 live births. Neonatal diabetes is due to a monogenic defect, and mutat…
Eligibility
- Age range
- 2–50 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Current age ≥2 years * Heterozygous for a V59M mutation in the KCNJ11 gene * Successfully transferred to oral sulphonylurea therapy * Willing to participate Exclusion Criteria: * Never able to transfer to oral sulphonylurea therapy * Unwilling to participate
Interventions
- DrugSulfonylurea
Glibenlclamide / glyburide
Locations (4)
- University of ChicagoChicago, Illinois
- University of RomeRome
- University of BergenBergen
- University of ExeterExeter