Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations

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

Methods: 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).

Results: 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.

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