MED23-associated refractory epilepsy successfully treated with the ketogenic diet

Area of Science:

• Genetics
• Neurology
• Metabolic Disorders

Background:

• Epilepsy is a neurological disorder characterized by recurrent seizures.
• Refractory epilepsy poses significant treatment challenges.
• Genetic factors play a crucial role in the etiology of epilepsy.

Observation:

• A 7.5-year-old boy with infantile onset global developmental delay and refractory epilepsy presented with microcephaly and truncal hypotonia.
• Brain MRI revealed delayed myelination and a thin corpus callosum.
• Whole exome sequencing identified a novel homozygous pathogenic variant (c.1937A>G; p.Gln646Arg) in the MED23 gene.

Findings:

• The identified MED23 variant is associated with refractory epilepsy and global developmental delay.
• MED23 is a key regulator of energy homeostasis and glucose production.
• Liver-specific Med23-knockout mice exhibit reduced gluconeogenesis and lower blood glucose levels.

Implications:

• This case expands the known phenotypic spectrum of MED23-related disorders.
• The findings suggest a potential mechanism for the complete response to the ketogenic diet in this patient.
• Identifying the genetic basis of refractory epilepsy can guide personalized treatment strategies.