Chorea-Acanthocytosis Presenting as Autosomal Recessive Epilepsy in a Family With a Novel VPS13A Mutation

Area of Science:

• Neurogenetics
• Movement Disorders
• Epileptology

Background:

• Chorea-acanthocytosis (ChAc) is a rare autosomal recessive disorder typically presenting with movement abnormalities and acanthocytosis.
• Mutations in the VPS13A gene are the known cause of ChAc.
• This report details an unusual presentation within a consanguineous Turkish family.

Observation:

• Three siblings presented with seizures, with one diagnosed with temporal lobe epilepsy.
• Neuroimaging revealed basal ganglia involvement in the absence of overt movement disorders.
• [18F]FDG-PET and [123I]FP-CIT-SPECT demonstrated reduced striatal glucose metabolism and dopamine transporter availability, respectively.

Findings:

• Exome sequencing identified a novel homozygous VPS13A truncating mutation (c.4326 T>A, p.Tyr1442*) in affected siblings.
• This mutation segregated with the epilepsy phenotype in the family.
• Autosomal recessive epilepsy emerged as the predominant clinical manifestation.

Implications:

• This case expands the phenotypic spectrum of Chorea-acanthocytosis, highlighting epilepsy as a potential primary presentation.
• The findings underscore the importance of genetic testing for VPS13A in epilepsy cases with unexplained basal ganglia abnormalities.
• This study contributes novel insights into the neurobiological underpinnings of ChAc and its variable clinical expressivity.