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.

Rapidly progressive frontotemporal dementia and bulbar amyotrophic lateral sclerosis in Portuguese patients with C9orf72 mutation.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) form a spectrum of clinically, pathologically, and genetically overlapping disorders, as confirmed by the recent report that it can be caused by a hexanucleotide repeat expansion in C9orf72. One hundred and fourteen Portuguese cases diagnosed as probable or possible familial FTLD, as part of the EOD consortium study, and nine further Portuguese cases with familial ALS were tested for the presence of this mutation. Results showed that six Portuguese patients from unrelated families had the mutation, five (4.4%) patients from the FTLD group and one (11.1%) from the ALS sample. Of these, three patients had FTLD and rapidly progressive bulbar ALS. Electromyography confirmed diffuse loss of motor units with marked bulbar involvement. In conclusion, the cases now reported showed a very rapid progression, suggesting bulbar ALS could be particularly common and aggressive in patients with the C9orf72 hexanucleotide repeat expansion, in the Portuguese population.