Reverse Phenotyping: Addressing Refractory Seizures From an Endocrine Perspective.

Neonatal hypoglycemia (NH) is a common abnormality in newborns, posing significant morbidity risks. Prompt diagnosis and treatment are vital to mitigate brain damage and enhance outcomes. Congenital hyperinsulinemia (CHI) is a leading cause of recurrent hypoglycemia in infants, often stemming from genetic mutations such as in the GLUD1 gene, manifesting as hyperinsulinism-hyperammonemia syndrome (HI/HA). We present a case of a 2-year-old girl with refractory epilepsy, later identified as HI/HA, whose paroxysmal episodes mimicked multiple seizure types. Genetic testing revealed a heterozygous pathogenic mutation in exon 2 of the GLUD1 gene. Treatment with diazoxide significantly improved blood sugar levels and achieved effective seizure control. Our case underscores the significance of considering metabolic etiologies like hyperinsulinemic hypoglycemia in children with seizures resistant to standard antiepileptic drugs. Early recognition, genetic testing, and targeted therapy are pivotal for achieving seizure control and optimizing patient outcomes.