Fernandez-Ramos, Joaquin ADe-la-Torre-Aguilar, Maria JoseQuintans, BeatrizPerez-Navero, Juan LuisBeyer, KatrinLopez-Laso, Eduardo2023-05-032023-05-032021-11-25Fernández-Ramos JA, De la Torre-Aguilar MJ, Quintáns B, Pérez-Navero JL, Beyer K, López-Laso E, et al. Genetic landscape of Segawa disease in Spain. Long-term treatment outcomes. Parkinsonism Relat Disord. 2022 Jan;94:67-78http://hdl.handle.net/10668/22467In 2009, we described a possible founder effect of autosomal dominant Segawa disease in Córdoba (Spain) due to mutation c.265C>T (p. Q89*) in the GCH1 gene. We present a retrospective multicentre study aimed at improving our knowledge of Segawa disease in Spain and providing a detailed phenotypic-genotypic description of patients. Clinical-genetic information were obtained from standardized questionnaires that were completed by the neurologists attending children and/or adults from 16 Spanish hospitals. Eighty subjects belonging to 24 pedigrees had heterozygous mutations in GCH1. Seven genetic variants have been described only in our cohort of patients, 5 of which are novel mutations. Five families not previously described with p. Q89* were detected in Andalusia due to a possible founder effect. The median latency to diagnosis was 5 years (IQR 0-16). The most frequent signs and/or symptoms were lower limb dystonia (38/56, 67.8%, p = 0.008) and diurnal fluctuations (38/56, 67.8%, p = 0.008). Diurnal fluctuations were not present in the phenotypes other than dystonia. Fifty-three of 56 symptomatic patients were treated with a levodopa/decarboxylase inhibitor for (mean ± SD) 12.4 ± 8.12 years, with 81% at doses lower than 350 mg/day (≤5 mg/kg/d in children). Eleven of 53 (20%) patients had nonresponsive symptoms that affected daily life activities. Dyskinesias (4 subjects) were the most prominent adverse effects. This study identifies 5 novel mutations and supports the hypothesis of a founder effect of p. Q89* in Andalusia. New insights are provided for the phenotypes and long-term treatment responses, which may improve early recognition and therapeutic management.enAutosomal dominant GTPCH deficiencyAutosomal dominant Segawa diseaseDopa-responsive dystoniaDopamineDyskinesiasDystoniaFounder mutationGCH1GTPCHLevodopaParkinson's diseaseParkinsonismDystonic DisordersGTP CyclohydrolaseHumansLevodopaRetrospective StudiesSpainTreatment Outcomeresearch article34890878Restricted AccessMutaciónEfecto FundadorDistoníaExtremidad InferiorDiscinesiasCarboxiliasasNeurólogos10.1016/j.parkreldis.2021.11.0141873-5126