Long-term follow up of four patients with dopa-responsive dystonia

Objective To investigate the clinical characteristics，treatment effect，long-term follow up results，guanosine triphosphate (GTP) cyrclohydrolaseⅠ (GCHⅠ) gene and tyrosine hydroxylase (TH) gene mutations in patients with dopa-responsive dystonia (DRD). Methods The clinical features of 3 families with 4 affected members were analyzed and all of 4 patients were screened for mutations of the GCHⅠgene and TH gene with DNA sequences. Results Four patients were females，average age at onset was (15.3±5.6) years (range: from 9 to 20 years).The initial symptoms were a gait disorder，stiffness or tremor of the lower limbs in all patients presented with diurnal fluctuation.As the increase of disease duration，bilateral hand tremor was found in three patients，systemic torsion was found in one patient and torticollis was found in one patient.All patients’symptoms were in complete remission after administration of low dose of levodopa.Four patients were followed up for 0.5 to 10.0 years，and all were still responsive to the levodopa treatment and effective dosage was decreased as the increase of the disease duration.No long-term side effects of levodopa had occurred after long-term treatment.One patient was found to have c.607G>A (p.Gly203 Arg) heterogenetic mutation in GCHⅠ gene.Molecular analysis revealed a compound heterozygous mutation in the TH gene (p.Y447Ter and p.V468M) in one patient.No point mutations in both genes were found in other patients. Conclusions DRD patients have dramatic and sustained response to levodopa and no long-term side effects of levodopa after long-term treatment.The detection of GCHⅠand TH gene mutations is helpful in early diagnosis but the negative results could not exclude the diagnosis of DRD. Key words: Dystonia; Levodopa; GTP cyclohydrolase; Tyrosine 3-monooxygenase; Follow-up studies