• α-synuclein Parkinson's disease;
  • clinical phenotype;
  • familial Parkinson's disease

An Ala53Thr mutation of the α-synuclein has been recently identified as a rare cause of familial Parkinson's disease (fPD). In the present study, the clinical characteristics of Parkinson's disease (PD) patients with Ala53Thr α-synuclein mutation (α-synPD) were compared with fPD patients without any known mutation. An investigator blinded to the results of the genetic analysis examined 15 α-synPD patients and 43 consecutive fPD patients. Demographic data, age at onset of the illness, duration of the disease and modality of presentation were collected. Segregation ratios for both sexes in individuals at risk of developing α-synPD were estimated. The Unified Parkinson's disease rating scale (UPDRS) was also completed. The 15 α-synPD patients were matched for duration of the disease and age at onset with 15 of the 43 fPD patients (MfPD). Comparisons were also made between 14 patients belonging to three multicase families with patterns of inheritance similar to α-synPD. The α-synPD patients were significantly younger (mean difference 11.8 years) and showed the first sign of the disease earlier in life (mean difference 12.7 years) as compared with the fPD patients. Tremor at onset was present in only one (6.7%) of the α -synPD patients compared with 18 (41.9%) of the fPD patients (P = 0.01). At the time of examination rigidity, postural instability, orthostatic hypotension and the overall clinical severity did not differ significantly either between α-synPD and fPD or between α-synPD and MfPD groups. Nevertheless, some clinically relevant trends concerning the psychiatric symptoms and complications of therapy were recognized. The overall clinical severity and the progression of the disease in patients with α-synPD did not differ from that of the fPD patients. The α-synPD patients presented the illness at a younger age and also had lower prevalence of tremor when compared with the fPD patients.