Pharmacological and nutritional treatment for McArdle's disease (Glycogen Storage Disease type V).

BACKGROUND: McArdle's disease (Glycogen Storage Disease type V) is caused by the absence of the glycolytic enzyme, muscle phosphorylase. Patients present with exercise-induced pain, cramps, fatigue, myoglobinuria and acute renal failure, which can ensue if the myoglobinuria is severe.

OBJECTIVES: To systematically review the evidence from randomised controlled trials of pharmacological or nutritional treatments in improving exercise performance and quality of life in McArdle's disease.

SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group register (searched December 2001 and updated in December 2003), MEDLINE (January 1966 to December 2003) and EMBASE (January 1980 to December 2003) using the search term 'McArdle's disease and it's synonym 'Glycogen Storage Disease type V'.

SELECTION CRITERIA: We included randomised controlled trials (including crossover studies) and quasi-randomised trials. Open trials and individual patient studies with no patient or observer blinding were included in the discussion but not the review. Types of interventions included any pharmacological agent or micronutrient or macronutrient supplementation. Primary outcome measures included any objective assessment of exercise endurance (for example VO2 max, walking speed, muscle force/power and improvement in fatiguability). Secondary outcome measures included metabolic changes (such as reduced plasma creatine kinase activity and a reduction in the frequency of myoglobinuria); subjective measures (including quality of life scores and indices of disability); and serious adverse events.

DATA COLLECTION AND ANALYSIS: Two reviewers checked the titles and abstracts identified by the search, independently assessed methodological quality of the full text of potentially relevant studies and extracted data onto a specially designed form.

MAIN RESULTS: We reviewed 20 trials. Ten trials fulfilled the criteria for inclusion and ten trials were included in the discussion. The largest treatment trial included 19 cases, the other trials included fewer than 12 cases. As there were only single trials for a given intervention we were unable to undertake a meta-analysis.

REVIEWERS' CONCLUSIONS: It is not yet possible to recommend any specific treatment for McArdle's disease. Low dose creatine supplementation was shown to demonstrate a statistically significant benefit, albeit modest, in ischaemic exercise in a small number of patients. Ingestion of oral sucrose immediately prior to exercise reduces perceived ratings of exertion and heart rate and improves exercise tolerance. This treatment will not influence sustained or unexpected exercise and may cause significant weight gain. Because of the rarity of McArdle's disease, there is a need to develop multicentre collaboration and standardised assessment protocols for future treatment trials.