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 glutamate and glutamine
/creatine (Glx/Cr) in the striatum in one case. One patient died during
sleep, another was treated with DBS which transiently attenuated feeding
dystonia but not his gait disorder or chorea. Conclusions: Larger
longitudinal neuroimaging studies with different modalities, particularly
MRS, are needed in order to determine their potential role as biomarker/s
for ChAc.