Genetic landscape of Segawa disease in Spain. Long-term treatment outcomes
| Autor: | Matthew Martin, Katrin Beyer, Juan Luis Pérez-Navero, Eduardo López-Laso, Matias Mora, L. González Gutierrez-Solana, J. Martínez-Ruiz, J. Hernandez-Vara, M. Llorente, Á. García Cazorla, Juan-Luis Ramos, Rafael Artuch, María José de la Torre-Aguilar, J. Serrano Cárdenas, Pablo Mir, Beatriz Quintáns, M.J. Sobrido Gómez, A. Adarmes, J.J. Ochoa Sepúlveda, M.D. Teva, C. Castaño-de la Mota, J.C. Gómez-Esteban, Joaquín A. Fernández-Ramos, E. Moreno-Medinilla |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
GTPCH
Pediatrics medicine.medical_specialty Levodopa Dopamine Parkinson's disease Decarboxylase inhibitor Pedigree chart Disease Autosomal dominant Segawa disease Parkinsonism medicine Humans Founder mutation GTP Cyclohydrolase Adverse effect Retrospective Studies Dystonia Dyskinesias business.industry medicine.disease Dopa-responsive dystonia Autosomal dominant GTPCH deficiency Treatment Outcome Neurology Dystonic Disorders Spain Cohort Neurology (clinical) Geriatrics and Gerontology business GCH1 Founder effect medicine.drug |
| Zdroj: | Parkinsonism & Related Disorders. 94:67-78 |
| ISSN: | 1353-8020 |
| Popis: | Introduction In 2009, we described a possible founder effect of autosomal dominant Segawa disease in Cordoba (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. Methods Clinical-genetic information were obtained from standardized questionnaires that were completed by the neurologists attending children and/or adults from 16 Spanish hospitals. Results 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 non-responsive symptoms that affected daily life activities. Dyskinesias (4 subjects) were the most prominent adverse effects. Conclusion 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect