Phenotypic variability in chorea-acanthocytosis associated with novel <i>VPS13A</i> mutations
Valter Niemelä, Ammar T. Salih, Daniela Solea, Björn Lindvall, Jan Weinberg, G. Miltenberger, Tobias Granberg, Aikaterini Tzovla, Love Engström Nordin, Torsten Danfors, Irina Savitcheva, Niklas Dahl, Martin Paucar
Abstract
<h3>Objective</h3> To perform a comprehensive characterization of a cohort of patients with chorea-acanthocytosis (ChAc) in Sweden. <h3>Methods</h3> Clinical assessments, targeted genetic studies, neuroimaging with MRI, [<sup>18</sup>F]-fluorodeoxyglucose (FDG) PET, and dopamine transporter with <sup>123</sup>I FP-CIT (DaTscan) SPECT. One patient underwent magnetic resonance spectroscopy (MRS). <h3>Results</h3> Four patients living in Sweden but with different ethnical backgrounds were included. Their clinical features were variable. Biallelic <i>VPS13A</i> 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. <h3>Conclusions</h3> Larger longitudinal neuroimaging studies with different modalities, particularly MRS, are needed to determine their potential role as biomarkers for ChAc.