Clinical and imaging findings in Parkinson disease associated with the A53E SNCA mutation

To describe the clinical features and brain imaging findings of autosomal dominant Parkinson disease (PD) associated with a recently reported mutation in SNCA.

A Finnish family with PD in 3 successive generations, in accordance with an autosomal dominant inheritance pattern, was identified. We examined 2 available members of the family, the female proband and her daughter (both with early-onset PD), clinically and using dopamine transporter imaging ([(123)I]FP-CIT SPECT). A possible causative genetic defect was investigated by molecular genetic analyses.

A heterozygous c.158C>A (p.A53E) point mutation in SNCA was revealed in both patients. The patients presented with PD clinically characterized by severe bradykinesia but with very little tremor and early onset of levodopa-induced dyskinesia. No cognitive decline or dysautonomic features have emerged during more than 5 years of follow-up. Both patients presented with a severe striatal binding defect in dopamine transporter SPECT imaging.

The results of this observational study add evidence to the suggestion that the p.A53E mutation in SNCA is indeed pathogenic and results in autosomal dominant PD. Bradykinesia and early onset of levodopa-induced dyskinesia are the characteristic clinical features associated with the A53E mutation, but the patients did not exhibit dementia or dysautonomia. The [(123)I]FP-CIT SPECT findings indicated a profound, symmetric dopaminergic defect, in contrast to those observed in patients with idiopathic PD.