P-489: Incomplete DEND syndrome due to a homozygous ABCC8 mutation in a 14-year-old girl with diabetes mellitus, neurodevelopmental delay, and epilepsy
S Lekka, M M Rossolatou, A Mertzanian, I Kosteria, A Sertedaki, M Kafetzi, S Fakiolas, C Kanaka-Gantenbein, E -A VlachopapadopoulouAbstract
Introduction
Activating ABCC8 variants are linked to neonatal diabetes and ABCC8-MODY. These variants affect ATP-sensitive potassium (KATP) channels in pancreatic β-cells and the brain, leading to metabolic and neurological manifestations. Only a small subset of patients with neonatal diabetes due to KCNJ11, and fewer with ABCC8 variants, develop DEND syndrome (Developmental Delay, Epilepsy, Neonatal Diabetes) or its intermediate form.
Objectives
To report an adolescent with non-autoimmune diabetes, neurodevelopmental delay, and epilepsy, in whom a homozygous ABCC8 variant was identified, consistent with incomplete DEND syndrome.
Methods
A girl with a known mild developmental delay was followed since age 6.4 years for short stature (height declined from the 25th to the 3rd percentile). Medical history included polycystic kidney disease. Initial work-up revealed hypothyroidism, and LT4 treatment was initiated. At the age of 14 years, the patient presented with generalized epilepsy. Whole exome sequencing identified a pathogenic 15q11.2 deletion, consistent with developmental delay. Concurrently, hyperglycemia was detected. A 2-hour OGTT confirmed diabetes (glucose: 0’ 101 mg/dL, 120’ 212 mg/dL), with preserved C-peptide and negative autoantibodies. Given the combination of endocrine, neurological, and developmental features, a supplementary targeted gene panel for monogenic diabetes was requested and revealed a homozygous ABCC8 variant of uncertain significance (c.4489G>A, p.Val1497Met). The girl is currently on CGM and receives no treatment.
Results
The phenotype of diabetes, epilepsy, and neurodevelopmental delay, in conjunction with the identified homozygous ABCC8 variant, is consistent with incomplete DEND syndrome
Conclusions
Variants in ABCC8 should be considered in patients with non-autoimmune diabetes and neurological manifestations. Recognition of this entity is clinically important, as treatment with sulfonylureas instead of insulin may improve glycemic control and, in some cases, neurological outcomes.