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Research paper
Genotypic and phenotypic features of McArdle disease: insights from the Spanish national registry
  1. Alejandro Lucia1,
  2. Jonatan R Ruiz2,3,
  3. Alfredo Santalla4,
  4. Gisela Nogales-Gadea5,6,
  5. Juan C Rubio6,7,
  6. Inés García-Consuegra6,7,
  7. Ana Cabello6,7,
  8. Margarita Pérez1,
  9. Susana Teijeira8,
  10. Irene Vieitez8,
  11. Carmen Navarro6,8,
  12. Joaquín Arenas6,7,
  13. Miguel A Martin6,7,
  14. Antoni L Andreu5,6
  1. 1Universidad Europea de Madrid, Madrid, Spain
  2. 2Departmento de Educación Física, Facultad de Ciencias del Deporte, Universidad de Granada, Granada, Spain
  3. 3Department of Biosciences and Nutrition at NOVUM, Unit for Preventive Nutrition, Karolinska Institutet, Stockholm, Sweden
  4. 4Facultad de CC Actividad Física y el Deporte, Universidad Pablo Olavide, Sevilla, Spain
  5. 5Laboratori de Patología Mitocondrial i Neuromuscular, Institut de Recerca Hospital Universitari Vall d'Hebron, Barcelona, Spain
  6. 6CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Spain
  7. 7Laboratorio de Enfermedades mitocondriales y neuromusculares, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain
  8. 8Servicio de Anatomia Patológica, Hospital Universitario de Vigo (Meixoeiro), Vigo, Spain
  1. Correspondence to Dr A L Andreu, Laboratori de Patología Mitocondrial i Neuromuscular, Institut de Recerca Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain; aandreu{at}


Background Published genotype/phenotype data on McArdle disease are limited in sample size. A single national (Spanish) registry of patients with McArdle disease was created with the purpose of analysing their genotypic and phenotypic characteristics.

Methods A cross sectional study was conducted, collecting demographic, family history, clinical, genotype and functional capacity data from all patients diagnosed with McArdle disease in the Spanish National Health System up to December 2010.

Results 239 cases were recorded (all of Caucasian descent, 102 women; mean±SD age 44±18 years (range 9, 93)); prevalence of ∼1/167 000 people. Two mutant PYGM alleles were identified in 99.6% of cases. Although there was heterogeneity in the severity of symptoms, there were four common diagnostic features: (1) 99.5% of patients reported a history of acute crises of exercise intolerance (accompanied by recurrent myoglobinuria in 50% of cases); (2) in 58% of patients, symptoms started in the first decade of life; (3) 86% of patients repeatedly experienced the ‘second wind’ phenomenon over life; and (4) 99% of patients had a high basal serum level of total creatine kinase (>200 U/l). Clinical presentation of the disease was similar in men and women and worsened with age. Patients who were physically active had higher levels of cardiorespiratory fitness (by 23%, p=0.003) and were more likely to improve their clinical course over a 4 year period compared with inactive patients (OR 225; 95% CI 20.3 to 2496.7).

Conclusions The main clinical features of McArdle disease are generally homogeneous and frequently appear during childhood; clinical condition deteriorates with ageing. Active patients have a better clinical outcome and functional capacity.

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  • AL, JRR, MAM and ALA contributed equally to this paper.

  • Funding This study was supported in part by grants from the Spanish Ministry of Science and Innovation (FIS PI10/00036, PI 10/02628, PI09-00194, RD09/0076/00011, and RYC-2010-05957) and from the Isabel Gemio Foundation for Neuromuscular and Other Rare Diseases. JCR and IG-C are recipients of contracts from SMSI (CA 05-0039 and CA 08-0203, respectively).

  • Competing interests None.

  • Ethics approval Ethics approval was provided by the institutional review boards of Hospital 12 de Octubre (Madrid), Val Hebron, Hospital Moixeiro and Universidad Europea de Madrid.

  • Provenance and peer review Not commissioned; externally peer reviewed.