RT Journal Article
T1 Genetic landscape of Segawa disease in Spain. Long-term treatment outcomes.
A1 Fernandez-Ramos, Joaquin A
A1 De-la-Torre-Aguilar, Maria Jose
A1 Quintans, Beatriz
A1 Perez-Navero, Juan Luis
A1 Beyer, Katrin
A1 Lopez-Laso, Eduardo
K1 Autosomal dominant GTPCH deficiency
K1 Autosomal dominant Segawa disease
K1 Dopa-responsive dystonia
K1 Dopamine
K1 Dyskinesias
K1 Dystonia
K1 Founder mutation
K1 GCH1
K1 GTPCH
K1 Levodopa
K1 Parkinson's disease
K1 Parkinsonism
AB In 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.
PB Elsevier
YR 2021
FD 2021-11-25
LK http://hdl.handle.net/10668/22467
UL http://hdl.handle.net/10668/22467
LA en
NO Fernández-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;94:67-78
DS RISalud
RD Apr 6, 2025