Santalla Hernández, AlfredoNogales-Gadea, GiselaBlázquez Encinar, AlbertoVieitez, IreneGonzález Quintana, AdriánSerrano Lorenzo, PabloGarcía-Consuegra, InésAsensio Peña, SaraBallester López, AlfonsinaPintos Morell, GuillemColl Cantí, JaumePareja Galeano, HeliosDíez Bermejo, JorgePérez Ruiz, MargaritaAndreu, Antoni L.Pinós, TomásArenas, JoaquínMartín, Miguel ÁngelLucía Mulas, Alejandro2017-11-302017-11-302017González-Quintana, A., Encinar, A. B., Lucia, A., Ballester-Lopez, A., Santalla, A., Andreu, A. L., ... & Vieitez, I. (2017). Genotypic and phenotypic features of all Spanish patients with McArdle disease: a 2016 update. BMC genomics, 18(8), 819.1471-2164http://hdl.handle.net/11268/6815BACKGROUND: 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/McArdle diseasejournal article10.1186/s12864-017-4188-2open accessGenéticaGenética humanaBiotecnología