Clinical, pathologic and genetic studies on autosomal recessive early-onset parkinsonism with diurnal fluctuation.

To clarify the genetic mode and clinical characteristics of familial early-onset parkinsonism with diurnal fluctuation, we studied 43 patients from 22 families. The estimated segregation ratio (0.2963) and absence of gender preponderance indicated autosomal recessive inheritance. Clinical features included the average age at onset of 26.1 years, parkinsonism with marked diurnal fluctuation, remarkable effect of levodopa, dyskinesias, dystonia, hyperreflexia, absence of dementia, and a benign course; autonomic symptoms were only mild if present. Autopsy study in one of our patients disclosed neuronal loss without Lewy bodies and the presence of melanin-poor neurons in the substantia nigra. Linkage analysis on 16 families mapped the disease gene to chromosome 6q25.2-27.