Study On Clinical Characteristics And Causative Gene Of Dopa-responsive Dystonia

Background: Dopa-responsive dystonia (DRD) is an eminently treatable dystonia. Its recognition is therefore of crucial importance. It is characterised by childhood onset dystonia but a wide range of clinical presentations has now been described. Disorder is typically characterized by low levels of the neurotransmitter metabolite homovanillic acid and reduced levels of neopterin and tetrahydrobiopterin (BH4) in the cerebrospinal fluid. This is due to heterozygote mutations of the GTP cyclohydrolase I gene, which is the rate-limiting enzyme in the synthesis of BH4. BH4 is an essential co-factor for tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of dopamine. Reduced levels of BH4 lead to the dopamine-deficit syndrome DRD because of reduced TH activity. Objective: To investigate the clinical characteristics and mutations of GCH I gene of patients with DRD.Methods: Four families with 26 affected family members and one unaffected family member and 10 patients with sporadic DRD were examined.Interview, physical examination and CT/MR scan were performed.Mutation screening was performed using single-strand conformation polymorphism analysis followed by direct sequencing of the presumably mutated exons.Results: The average onset age was 16.7 ± 12.6 years. Patients with onset in childhood tended to start with dystonia. Those with onset in adulthood start with Parkinsonism or dystonia. The clinical manifestations were depended on the age. CT/MR scan were normal. All of 26 cases showed marked and sustained response...