Autosomal recessive early-onset parkinsonism with diurnal fluctuation: clinicopathologic characteristics and molecular genetic identification

Autosomal recessive early-onset parkinsonism with diurnal fluctuation (AR-E PDF, syn. autosomal recessive juvenile parkinsonism, PARK2) is one of the h ereditary parkinsonian syndromes. We examined subjects consisting of 43 pat ients from 22 families with AR-EPDF. The clinical features were relatively homogeneous, including the average age at onset of 26.1 years, beginning wi th dystonic gait disturbance, diurnal fluctuation of the symptoms (sleep be nefit) unrelated to medication, dystonia (mainly foot dystonia), hyperactiv e tendon reflex, remarkable effect of levodopa and other antiparkinsonism d rugs, susceptibility to dopa-induced dyskinesia, mild autonomic symptoms, a bsence of dementia, and slow progression of disease. Some patients had hyst eric character or psychic symptoms provoked by medication. Pathologic study revealed neuronal loss in the substantia nigra pars compacta and locus coe ruleus without Lewy body formation. We performed extensive molecular geneti c analysis of the parkin gene in 16 families to identify a total of six dif ferent deletional mutations. In AR-EPDF loss of newly discovered 'Parkin' p rotein is responsible for selective degeneration of the pigmented neurons i n the substantia nigra and locus coeruleus. Compared with autosomal dominan t Parkinson's disease, AR-EPDF appears to be more prevalent and present in several ethnic groups. (C) 2000 Elsevier Science B.V. All rights reserved.