Segawa Dopa-Responsive Dystonia☆

Autosomal dominant GTP cyclohydrolase I (GCH-I) deficiency is an autosomal dominant dopa responsive dystonia caused by heterozygous mutation of the GCH-I gene located on 14q22.1–q22.2. Although a number of mutations have been reported, the change remains highly stable within families and causes decrease of tyrosine hydroxylase protein at the nigrostriatal (NS)–dopamine (DA) neuron terminal. In addition, decreased tetrahydrobiopterin (BH 4 ) levels early in the development affect DA receptors age dependently and produce a spectrum of specific symptoms attributed to neuronal changes traced to processes of the development of the NS–DA neuron, related striatal projection neurons, and the output projection of the basal ganglia.