Background: DEND syndrome is characterized by developmental delay, epilepsy, and neonatal diabetes mellitus (NDM) due to mutations in KCNJ11 and ABCC8 genes. Intermediate DEND (iDEND) syndrome is a rare mild form with mild motor, speech or cognitive delay and an absence of epilepsy. Improvement in glycemic control and neurologic symptoms has been reported in three cases with iDEND syndrome.
Objective and hypotheses: To present the results of sulphonylurea therapy in a 17-year-old girl with iDEND syndrome.
Method: The patient was diagnosed with NDM at the age of two months. Her motor and cognitive development was delayed (IQ score: 49) and she was diagnosed with attention deficit and hyperactivity disorder. There was no history of epilepsy. She was on insulin therapy at a dose of 1.2 U/kg/day. Random C peptid level was <0.1 ng/ml, diabetes auto-antibodies were negative and HbA1c was 10.9%. There was no history of severe hypoglycemic attacks to explain her mental retardation.
Results: Genetic analysis revealed a heterozygous missense mutation in the KCJN11 gene (p.V59M). Glibenclamide was started at a dose of 0.1 mg/kg/day and the dose was increased gradually up to 1.3 mg/kg/day. After glibenclamide, HbA1c level (10.98%) and daily insulin requirement (1.20.9 U/kg/day) were reduced and C-peptide level (<0.10.68 ng/ml) was increased. However, insulin could not be weaned-off and no clinically significant improvement in the patients cognitive functions was observed.
Conclusion: Previously, sulphonylurea treatment has been reported to improve neurologic symtomps in iDEND sndrome. In our case, although glycemic control was improved and daily insulin requirement was decreased, there was no clinically significant improvement in cognitive functions possibly due to late diagnosis. DEND syndrome should be considered in NDM patients with neurological findings and sulphonylurea should be started as soon as possible.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology