Dopa-responsive dystonia

Clinical characteristics and pahophysiologies of dopa-responsive dystonia are discussed by reviewing autosomal-dominant GTP cyclohydrolase-I deficiency (AD GCHI D), recessive deficiencies of enzymes of pteridine metabolism, and recessive tyrosine hydroxylase (TH). Pteridine and TH metabolism involve TH activities in the terminals of the nigrostriatal dopamine neuron which show high in early childhood and decrease exponentially with age, attaining stational low levels by the early 20s. In these disorders, TH in the terminals follows this course with low levels and develops particular symptoms with functional maturation of the downstream structures of the basal ganglia; postural dystonia through the direct pathway and descending output matured earlier in early childhood and parkinsonism in TH deficiency in teens through the D2 indirect pathway ascending output matured later. In action-type AD GCHI D, deficiency of TH in the terminal on the subthalamic nucleus develops action dystonia through the descending output in childhood, focal and segmental dystonia and parkinsonism in adolescence and adulthood through the ascending pathway maturing later. Dysfunction of dopamine in the terminals does not cause degenerative changes or higher cortical dysfunction. In recessive disorders, hypofunction of serotonin and noradrenaline induces hypofunction of the dopamine in the perikaryon and shows cortical dysfunction.