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| Pàgina inicial > Articles > Articles publicats > Genotypic and phenotypic features of all Spanish patients with McArdle disease : |
(Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12)) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Universidad Europea de Madrid) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Instituto de Salud Carlos III) (Universidad Europea de Madrid)
| Data: | 2017 |
| Resum: | 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. |
| Ajuts: | Ministerio de Economía y Competitividad PI15/00558 Ministerio de Economía y Competitividad PI12/00914 Ministerio de Economía y Competitividad PI16/01492 Ministerio de Economía y Competitividad PI13/00855 Ministerio de Economía y Competitividad PI14/00903 Ministerio de Economía y Competitividad PI15/ 01756 Ministerio de Economía y Competitividad PI15/00431 Ministerio de Economía y Competitividad CD14/00032 |
| Drets: | Aquest 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.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | McArdle disease ; Spanish patients ; Genotype ; Phenotype ; Glycogenosis type V |
| Publicat a: | BMC genomics, Vol. 18 (november 2017) , ISSN 1471-2164 |
