Genotypic and phenotypic features of all Spanish patients with McArdle disease: a 2016 update.

Autor:	Santalla A; Universidad Pablo de Olavide, Sevilla, Spain.; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain., Nogales-Gadea G; Grup de Recerca en Malalties Neuromusculars i Neuropediatriques, Department of Neurosciences, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Camí de les Escoles, s/n 08916, (Barcelona), Badalona, Spain. gnogales@igtp.cat.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain. gnogales@igtp.cat., Encinar AB; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.; Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain., Vieitez I; Rare Diseases and Pediatric Medicine Group, Galicia Sur Health Research Institute, Complexo Hospitalario Universitario de Vigo (CHUVI), SERGAS, Vigo, Spain., González-Quintana A; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain., Serrano-Lorenzo P; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain., Consuegra IG; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.; Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain., Asensio S; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain., Ballester-Lopez A; Grup de Recerca en Malalties Neuromusculars i Neuropediatriques, Department of Neurosciences, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Camí de les Escoles, s/n 08916, (Barcelona), Badalona, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain., Pintos-Morell G; Grup de Recerca en Malalties Neuromusculars i Neuropediatriques, Department of Neurosciences, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Camí de les Escoles, s/n 08916, (Barcelona), Badalona, Spain.; Servicio de Pediatría, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain., Coll-Cantí J; Grup de Recerca en Malalties Neuromusculars i Neuropediatriques, Department of Neurosciences, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Camí de les Escoles, s/n 08916, (Barcelona), Badalona, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.; Servicio de Neurología, Hospital Universitari Germans Trias i Pujol, Badalona, Spain., Pareja-Galeano H; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.; Universidad Europea de Madrid, Madrid, Spain., Díez-Bermejo J; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.; Universidad Europea de Madrid, Madrid, Spain., Pérez M; Universidad Europea de Madrid, Madrid, Spain., Andreu AL; Departament de Patologia Mitocondrial i Neuromuscular, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autónoma de Barcelona, Barcelona, Spain., Pinós T; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.; Departament de Patologia Mitocondrial i Neuromuscular, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autónoma de Barcelona, Barcelona, Spain., Arenas J; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain., Martín MA; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.; Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain., Lucia A; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.; Universidad Europea de Madrid, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	BMC genomics [BMC Genomics] 2017 Nov 14; Vol. 18 (Suppl 8), pp. 819. Date of Electronic Publication: 2017 Nov 14.
DOI:	10.1186/s12864-017-4188-2
Abstrakt:	Background: We recently described the genotype/phenotype features of all Spanish patients diagnosed with McArdle disease as of January 2011 (n = 239, prevalence of ~1/167,000) (J Neurol Neurosurg Psychiatry 2012;83:322-8). Several caveats were however identified suggesting that the prevalence of the disease is actually higher. Methods: We have now updated main genotype/phenotype data, as well as potential associations within/between them, of all Spanish individuals currently diagnosed with McArdle disease (December 2016). Results: Ninety-four new patients (all Caucasian) have been diagnosed, yielding a prevalence of ~1/139,543 individuals. Around 55% of the mutated alleles have the commonest PYGM pathogenic mutation p.R50X, whereas p.W798R and p.G205S account for 10 and 9% of the allelic variants, respectively. Seven new mutations were identified: p.H35R, p.R70C, p.R94Q, p.L132WfsX163, p.Q176P, p.R576Q, and c.244-3_244-2CA. Almost all patients show exercise intolerance, the second wind phenomenon and high serum creatine kinase activity. There is, however, heterogeneity in clinical severity, with 8% of patients being asymptomatic during normal daily life, and 21% showing limitations during daily activities and fixed muscle weakness. A major remaining challenge is one of diagnosis, which is often delayed until the third decade of life in 72% of new patients despite the vast majority (86%) reporting symptoms before 20 years. An important development is the growing proportion of those reporting a 4-year improvement in disease severity (now 34%) and following an active lifestyle (50%). Physically active patients are more likely to report an improvement after a 4-year period in the clinical course of the disease than their inactive peers (odds ratio: 13.98; 95% confidence interval: 5.6, 34.9; p < 0.001). Peak oxygen uptake is also higher in the former (20.7 ± 6.0 vs. 16.8 ± 5.3 mL/kg/min, p = 0.0013). Finally, there is no association between PYGM genotype and phenotype manifestation of the disease. Conclusions: The reported prevalence of McArdle disease grows exponentially despite frequent, long delays in genetic diagnosis, suggesting that many patients remain undiagnosed. Until a genetic cure is available (which is not predicted in the near future), current epidemiologic data support that adoption of an active lifestyle is the best medicine for these patients.
Databáze:	MEDLINE
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