2026 American Academy of Neurology Abstract Website

Objective:

Describe two patients with chorea-acanthocytosis, a rare genetic disease.

Background:

Chorea-acanthocytosis, or VPS13A disease, is an autosomal-recessive neurodegenerative disorder caused by biallelic pathogenic variants in the VPS13A gene. It typically presents in early adulthood with progressive chorea, dystonia, or parkinsonism, often involving orofacial muscles. Additional features may include psychiatric symptoms, seizures, peripheral neuropathy, and caudate atrophy. We present two cases to illustrate the disease's clinical variability and features to support early recognition.

Design/Methods:

Case 1: 34-year-old Qatari man with achondroplasia developed progressive gait abnormalities, orofacial dyskinesias, and psychosis. Examination revealed bilateral foot drop, distal leg weakness, hyporeflexia, and cerebellar signs. MRI showed diffuse cerebral atrophy and caudate head atrophy. EMG suggested a chronic neurogenic process. He experienced severe leg pain, which improved alongside psychosis and dyskinesias with low-dose aripiprazole.

Case 2: 39-year-old Marshallese man presented with seizure after a reported cerebellar stroke. He subsequently developed progressive motor and cognitive decline, involuntary movements, dysphagia requiring PEG placement, and behavioral changes. Examination showed generalized weakness, adventitious facial and truncal movements, dysarthria, and sensory loss. MRI revealed mild caudate and midbrain atrophy. EMG suggested motor neuron disease. Treatment with riluzole helped stabilize symptoms six years after onset.

Results:

Case 1: Exome sequencing revealed a pathogenic homozygous variant in VPS13A gene c.6392 C>A, p.(S2131*).

Case 2: Exome sequencing identified compound heterozygous variants in VPS13A, c.4863+2T>C (intronic), likely pathogenic and c.386-24A>T (intronic), variant of uncertain significance. Given the absence from population databases and predicted deleterious nature of the uncertain variant, this result was felt to be diagnostic by the clinical team.

Both patients demonstrated symptom plateau after supportive therapy.

Conclusions:

These cases reinforce the clinical heterogeneity of chorea-acanthocytosis, which can mimic Huntington disease. While no cure exists, early recognition can guide supportive care and counseling. The pathophysiology involves impaired protein trafficking due to chorein deficiency, highlighting potential therapeutic targets.