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.