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 three 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 three patients. MRS demonstrated reduced N-acetylaspartate/creatine (NAA/Cr) ratio as well as mild elevation of both choline/creatine (Cho/Cr) and combined glut...