Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations

To perform a comprehensive characterization of a cohort of patients with chorea-acanthocytosis (ChAc) in Sweden.

Clinical assessments, targeted genetic studies, neuroimaging with MRI, [¹⁸F]-fluorodeoxyglucose (FDG) PET, and dopamine transporter with ¹²³I FP-CIT (DaTscan) SPECT. One patient underwent magnetic resonance spectroscopy (MRS).

Four patients living in Sweden but with different ethnical backgrounds were included. Their clinical features were variable. Biallelic VPS13A mutations were confirmed in all patients, including 3 novel mutations. All tested patients had either low or absent chorein levels. One patient had progressive caudate atrophy. Investigation using FDG-PET revealed severe bilateral striatal hypometabolism, and DaTscan SPECT displayed presynaptic dopaminergic deficiency in 3 patients. MRS demonstrated reduced N-acetylaspartate/creatine (Cr) ratio and mild elevation of both choline/Cr and combined glutamate and glutamine/Cr in the striatum in 1 case. One patient died during sleep, and another was treated with deep brain stimulation, which transiently attenuated feeding dystonia but not his gait disorder or chorea.

Larger longitudinal neuroimaging studies with different modalities, particularly MRS, are needed to determine their potential role as biomarkers for ChAc.