[Japanese originality, clinical symptoms to the causative gene 1 Segawa disease]

Segawa disease was first reported in 1971 as 'Hereditary progressive basal ganglia disease with marked diurnal fluctuation'. In 1976, after experience of a 51 year old patient with 43 years non-treatment periods, I confirmed this disease as dystonia. Polysomnographies revealed selective involvement of the dopamine (DA) neuron without involvement of the D2 receptors. These were confirmed by PET studies performed early 90's. The clinical course of this adult patient was correlated to the age variation of the activities of tyrosine hydroxylase (TH) in the striatum and suggested non-progressive decrease of TH at the terminal of the nigrostriatal DA neuron. Histochemical studies confirmed selective involvement of the D1-direct pathways without any pathological changes. In 1990, Fujita and Shintaku suggested the deficiency of the GTP cyclohydrolase I (GCH-I) as the cause of this disease. In 1993, Ichinose and his colleagues clarified the gene of GCH-I as the causative gene. After the discovery of the gene, it is realized that Segawa disease has two clinical types, postural dystonia and action dystonia. The latter with involvement of the DA neuron innervating to the subthalamic nucleus with D1 receptor has focal or segmental dystonia or adult onset cases and provides phenotypical variation.