Genotypic and phenotypic features of all Spanish patients with McArdle disease

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...

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Autores: Santalla, Alfredo|||0000-0001-9418-0564, Nogales, Gisela|||0000-0002-7414-212X, Encinar, Alberto Blazquez, Vieitez, Irene, González-Quintana, Adrian, Serrano-Lorenzo, Pablo|||0000-0002-5661-7574, Consuegra-García, Inés, Asensio-Peña, Sara|||0000-0002-2048-5899, Ballester-Lopez, Alfonsina|||0000-0002-8922-1664, Pintos-Morell, Guillem|||0000-0002-9347-2386, Coll-Cantí, Jaume|||0000-0001-7128-1186, Pareja-Galeano, Helios, Díez-Bermejo, Jorge, Pérez Ruiz, Margarita|||0000-0001-7240-2082, Andreu Périz, Antoni Lluís, Pinós Figueras, Tomàs|||0000-0002-4379-0917, Arenas, Joaquín|||0000-0002-2877-5049, Martín, Miguel A.|||0000-0003-4741-772X, Lucia, Alejandro|||0000-0002-3025-2060
Formato: artículo
Fecha de publicación:2017
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:254036
Acesso em linha:https://ddd.uab.cat/record/254036
https://dx.doi.org/urn:doi:10.1186/s12864-017-4188-2
Access Level:acceso abierto
Palavra-chave:McArdle disease
Spanish patients
Genotype
Phenotype
Glycogenosis type V
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oai_identifier_str oai:ddd.uab.cat:254036
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Genotypic and phenotypic features of all Spanish patients with McArdle disease
a 2016 update
title Genotypic and phenotypic features of all Spanish patients with McArdle disease
spellingShingle Genotypic and phenotypic features of all Spanish patients with McArdle disease
Santalla, Alfredo|||0000-0001-9418-0564
McArdle disease
Spanish patients
Genotype
Phenotype
Glycogenosis type V
title_short Genotypic and phenotypic features of all Spanish patients with McArdle disease
title_full Genotypic and phenotypic features of all Spanish patients with McArdle disease
title_fullStr Genotypic and phenotypic features of all Spanish patients with McArdle disease
title_full_unstemmed Genotypic and phenotypic features of all Spanish patients with McArdle disease
title_sort Genotypic and phenotypic features of all Spanish patients with McArdle disease
dc.creator.none.fl_str_mv Santalla, Alfredo|||0000-0001-9418-0564
Nogales, Gisela|||0000-0002-7414-212X
Encinar, Alberto Blazquez
Vieitez, Irene
González-Quintana, Adrian
Serrano-Lorenzo, Pablo|||0000-0002-5661-7574
Consuegra-García, Inés
Asensio-Peña, Sara|||0000-0002-2048-5899
Ballester-Lopez, Alfonsina|||0000-0002-8922-1664
Pintos-Morell, Guillem|||0000-0002-9347-2386
Coll-Cantí, Jaume|||0000-0001-7128-1186
Pareja-Galeano, Helios
Díez-Bermejo, Jorge
Pérez Ruiz, Margarita|||0000-0001-7240-2082
Andreu Périz, Antoni Lluís
Pinós Figueras, Tomàs|||0000-0002-4379-0917
Arenas, Joaquín|||0000-0002-2877-5049
Martín, Miguel A.|||0000-0003-4741-772X
Lucia, Alejandro|||0000-0002-3025-2060
author Santalla, Alfredo|||0000-0001-9418-0564
author_facet Santalla, Alfredo|||0000-0001-9418-0564
Nogales, Gisela|||0000-0002-7414-212X
Encinar, Alberto Blazquez
Vieitez, Irene
González-Quintana, Adrian
Serrano-Lorenzo, Pablo|||0000-0002-5661-7574
Consuegra-García, Inés
Asensio-Peña, Sara|||0000-0002-2048-5899
Ballester-Lopez, Alfonsina|||0000-0002-8922-1664
Pintos-Morell, Guillem|||0000-0002-9347-2386
Coll-Cantí, Jaume|||0000-0001-7128-1186
Pareja-Galeano, Helios
Díez-Bermejo, Jorge
Pérez Ruiz, Margarita|||0000-0001-7240-2082
Andreu Périz, Antoni Lluís
Pinós Figueras, Tomàs|||0000-0002-4379-0917
Arenas, Joaquín|||0000-0002-2877-5049
Martín, Miguel A.|||0000-0003-4741-772X
Lucia, Alejandro|||0000-0002-3025-2060
author_role author
author2 Nogales, Gisela|||0000-0002-7414-212X
Encinar, Alberto Blazquez
Vieitez, Irene
González-Quintana, Adrian
Serrano-Lorenzo, Pablo|||0000-0002-5661-7574
Consuegra-García, Inés
Asensio-Peña, Sara|||0000-0002-2048-5899
Ballester-Lopez, Alfonsina|||0000-0002-8922-1664
Pintos-Morell, Guillem|||0000-0002-9347-2386
Coll-Cantí, Jaume|||0000-0001-7128-1186
Pareja-Galeano, Helios
Díez-Bermejo, Jorge
Pérez Ruiz, Margarita|||0000-0001-7240-2082
Andreu Périz, Antoni Lluís
Pinós Figueras, Tomàs|||0000-0002-4379-0917
Arenas, Joaquín|||0000-0002-2877-5049
Martín, Miguel A.|||0000-0003-4741-772X
Lucia, Alejandro|||0000-0002-3025-2060
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv McArdle disease
Spanish patients
Genotype
Phenotype
Glycogenosis type V
topic McArdle disease
Spanish patients
Genotype
Phenotype
Glycogenosis type V
description 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. 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). 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. 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.
publishDate 2017
dc.date.none.fl_str_mv 2
2017-01-01
2017
2017-01-01
dc.type.none.fl_str_mv Article
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VoR
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url https://ddd.uab.cat/record/254036
https://dx.doi.org/urn:doi:10.1186/s12864-017-4188-2
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/00558
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/00914
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Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/00903
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Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CD14/00032
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spelling Genotypic and phenotypic features of all Spanish patients with McArdle diseasea 2016 updateSantalla, Alfredo|||0000-0001-9418-0564Nogales, Gisela|||0000-0002-7414-212XEncinar, Alberto BlazquezVieitez, IreneGonzález-Quintana, AdrianSerrano-Lorenzo, Pablo|||0000-0002-5661-7574Consuegra-García, InésAsensio-Peña, Sara|||0000-0002-2048-5899Ballester-Lopez, Alfonsina|||0000-0002-8922-1664Pintos-Morell, Guillem|||0000-0002-9347-2386Coll-Cantí, Jaume|||0000-0001-7128-1186Pareja-Galeano, HeliosDíez-Bermejo, JorgePérez Ruiz, Margarita|||0000-0001-7240-2082Andreu Périz, Antoni LluísPinós Figueras, Tomàs|||0000-0002-4379-0917Arenas, Joaquín|||0000-0002-2877-5049Martín, Miguel A.|||0000-0003-4741-772XLucia, Alejandro|||0000-0002-3025-2060McArdle diseaseSpanish patientsGenotypePhenotypeGlycogenosis type VWe 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. 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). 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. 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. 22017-01-0120172017-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/254036https://dx.doi.org/urn:doi:10.1186/s12864-017-4188-2reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/00558Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/00914Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/01492Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/00855Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/00903Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/01756Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/00431Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CD14/00032open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2540362026-06-06T12:50:31Z
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