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Reverse Phenotyping: Addressing Refractory Seizures From an Endocrine Perspective
Shijiya Sherin1, Dhanya Soodhana2, Smilu Mohanlal3
1Department of Pediatrics, Aster Malabar Institute of Medical Sciences, Kozhikode, IND.
Insights
Congenital hyperinsulinemia (CHI) can cause recurrent infant hypoglycemia and seizures. Genetic testing identified a GLUD1 mutation in a child with refractory epilepsy, leading to successful diazoxide treatment.
Area of Science:
- Pediatric Neurology
- Endocrinology
- Medical Genetics
Background:
- Neonatal hypoglycemia (NH) is a common newborn condition with serious risks.
- Congenital hyperinsulinemia (CHI) is a primary cause of recurrent infant hypoglycemia, often due to genetic mutations like GLUD1, leading to hyperinsulinism-hyperammonemia (HI/HA).
Observation:
- A 2-year-old girl presented with refractory epilepsy and paroxysmal episodes mimicking various seizure types.
- Diagnostic workup revealed hyperinsulinism-hyperammonemia syndrome (HI/HA).
Findings:
- Genetic testing identified a heterozygous pathogenic mutation in exon 2 of the GLUD1 gene.
- Treatment with diazoxide effectively controlled blood glucose levels and resolved seizure activity.
Implications:
- This case highlights the importance of considering metabolic disorders, such as hyperinsulinemic hypoglycemia, in pediatric patients with intractable epilepsy.
- Early diagnosis through genetic testing and prompt, targeted therapy are crucial for managing HI/HA and improving seizure control and patient outcomes.
Abstract:
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.
