Objective: To investigate the clinical manifestations, treatment and genetic characteristics of dopa-responsive dystonia (DRD).

Background: Dopa-responsive dystonia (DRD) is resulted by variants of GCH1, TH and SPR. There was few report of clinical features and gene characteristics in Chinese children patients

Method: The clinical features，response to treatment and gene mutations of these patients were retrospectively summarized and analyzed.

Results: A total of 44 DRD patients with complete clinical data were collected, 28 were female and 16 were male. The onset age was 0 to 8 years (the median onset age was 1.4 years). The clinical manifestations were typical in 21 patients and atypical in 23 patients. 11 patients were triggered by infection or fever, 1 was by choking, and 32 were without any cause. Clinical symptoms were fluctuating, including diurnal fluctuation in 39 patients, fatigue aggravation in 40 patients, pressure aggravation in 33 patients, and infection aggravation in 25 patients. Five children with an atypical DRD phenotype developed episodes of status dystonicus. Family history was positive in 7 patients. Levodopa treatment was effective in all 44 cases, among which, the starting dose of 43 patients was 12.5 ~ 150mg/d (the median starting dose: 38mg/d), and the working time of levodopa treatment was 0.1 ~ 1440 hours (the median time: 24 hours). The symptoms of 24 patients disappeared after 4 ~ 548 days of levodopa treatment. During levodopa treatment, 11 patients presented with side effects, including dyskinesiaand/or irritability. One patient with SPR mutation changed to benzhexol treatment due to obvious levodopa induced dyskinesia. A total of 39 cases were followed up. The last follow-up age was between 1.1 and 15.9 years old, 35 patients could walk by themselves. 42 were detected with pathogenic variants of 3 different genes, including 13 with GCH1 pathogenic variants, 28 with TH pathogenic variants, and 1 with SPR pathogenic variants. The targeted gene panel results of the remaining 2 patients were negative.

Conclusion: The clinical manifestations of DRD in children can be both typical and atypical, and atypical DRD is not uncommon in children. TH mutations were the most common causative gene in Chinese DRD patients. In this study, 23 new variants of GCH1, TH and SPR genes were found in patients with DRD, which have not been reported in the literature.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-clinical-features-treatments-and-genetic-characteristics-in-chinese-children-with-dopa-responsive-dystonia/