The causative gene for dopa-responsive dystonia (DRD) is discovered to be that for guanosine triphosphate cyclohydrolase I (GCH), an enzyme involved in tetrahydrobiopterin biosynthesis. DRD patients are heterozygous in terms of the mutations. More than 70 mutations are found in this gene in DRD patients. A defective GCH gene results in a decreased biopterin content and thus in a decreased dopamine production in the brain. Analysis of the molecular etiology of DRD should help understand the pathophysiology of basal ganglia disorders, including Parkinson's disease. This chapter emphasizes that the nigro-striatal dopaminergic neurons are highly susceptible to a deficiency of tetrahydrobiopterin and the resulting defect in dopamine production. There are several types of dopa-responsive basal ganglia diseases. Parkinson's disease is the most well-known disease in that category. DRD is a disorder characterized by childhood or adolescent-onset of dystonia and by a dramatic response to low-dose L-dopa. DRD is also caused by dysfunction of nigro-striatal dopaminergic neurons, although its main symptom is dystonia, not parkinsonism. It is noted that blocking of dopamine receptors by neuroleptics produces a dystonic reaction in childhood, whereas in adults it results in parkinsonism. Parkinsonian symptoms sometimes appears later in DRD patients in adolescence.
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