GCH1 mutations in dopa-responsive dystonia and Parkinson ’s disease

AbstractGuanosine triphosphate cyclohydrolase I (GCH1) mutations are associated with increased risk for dopa-responsive dystonia (DRD) and Parkinson ’s disease (PD). Herein, we investigated the frequency ofGCH1 mutations and clinical symptoms in patients with clinically diagnosed PD and DRD. We used the Sanger method to screen entire exons in 268 patients with PD and 26 patients with DRD, with the examinations of brain magnetic resonance imaging scans, striatal dopamine transporter scans, and [123I] metaiodobenzylguanidine (MIBG) myocardiac scintigraphy scans. We identified 15 patients with heterozygousGCH1 mutations from seven probands and five sporadic cases. The prevalence ofGCH1 mutations in probands was different between PD [1.9% (5/268)] and DRD [26.9% (7/26)] (p value  <  0.0001). The onset age tends to be different between PD and DRD patients: 35.4 ± 25.3 and 16.5 ± 13.6, respectively (average ± SD;p = 0.08). Most of the patients were women (14/15). Dystonia was common symptom, and dysautonomia and cognitive decline were uncommon in our PD and DRD. All patients presented mild parkinsonism or dystonia with excellent response to levodopa. Seven of seven DRD and three of five PD presented norm al heart-to-mediastinum ratio on MIBG myocardial scintigraphy. Five of six DRD and three of four PD demonstrated normal densities of dopamine transporter. Our findings elucidated the clinical characteristics of PD and DRD patients due toGCH1 mutations. P...
Source: Journal of Neurology - Category: Neurology Source Type: research