A multidisciplinary study of patients with early-onset PD with and without parkin mutations

To establish phenotype-genotype correlations in early-onset Parkinson disease (EOPD), we performed neurologic, neuropsychological, and psychiatric evaluations in a series of patients with and without parkin mutations.

Parkin (PARK2) gene mutations are the major cause of autosomal recessive parkinsonism. The usual clinical features are early-onset typical PD with a slow clinical course, an excellent response to low doses of levodopa, frequent treatment-induced dyskinesias, and the absence of dementia.

A total of 44 patients with EOPD (21 with and 23 without parkin mutations) and 9 unaffected single heterozygous carriers of parkin mutations underwent extensive clinical, neuropsychological, and psychiatric examinations.

The neurologic, neuropsychological, and psychiatric features were similar in all patients, except for significantly lower daily doses of dopaminergic treatment and greater delay in the development of levodopa-related fluctuations (p < 0.05) in parkin mutation carriers compared to noncarriers. There was no major difference between the two groups in terms of general cognitive efficiency. Psychiatric manifestations (depression) were more frequent in patients than in healthy single heterozygous parkin carriers but did not differ between the two groups of patients.

Carriers of parkin mutations are clinically indistinguishable from other patients with young-onset Parkinson disease (PD) on an individual basis. Severe generalized loss of dopaminergic neurons in the substantia nigra pars compacta in these patients is associated with an excellent response to low doses of dopa-equivalent and delayed fluctuations, but cognitive impairment and special behavioral or psychiatric symptoms were not more severe than in other patients with early-onset PD.