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

McArdle disease (Glycogen Storage Disease type V) is caused by the absence of the glycolytic enzyme, muscle phosphorylase. People present with exercise-induced pain, cramps, fatigue, and myoglobinuria, which can result in acute renal failure if it is severe.

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

We updated the review by searching the Cochrane Neuromuscular Disease Group Trials Register (November 2007), MEDLINE (January 1966 to November 2007) and EMBASE (January 1980 to November 2007) using the search terms 'McArdle disease' and its synonym 'Glycogen Storage Disease type V'.

We included randomised controlled trials (including crossover studies) and quasi-randomised trials. Open trials and individual patient studies with no participant or observer blinding were included in the discussion. Types of interventions included any pharmacological agent or micronutrient or macronutrient supplementation. Primary outcome measures included any objective assessment of exercise endurance (for example aerobic capacity (VO(2)) max, walking speed, muscle force or 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.

Three review authors checked the titles and abstracts identified by the search and reviewed the manuscripts. Two review authors (RQ and RB) independently assessed methodological quality of the full text of potentially relevant studies and extracted data onto a specially designed form.

We reviewed 24 studies. Twelve trials fulfilled the criteria for inclusion, with two being first identified in this update. The 12 excluded trials are 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.

There is no evidence of significant benefit from any specific nutritional or pharmacological treatment in McArdle disease. In one small trial low dose creatine produced slight benefit but high dose creatine caused myalgia. Ingestion of oral sucrose immediately before exercise reduced perceived ratings of exertion and heart rate and improved exercise tolerance. This treatment will not influence sustained or unexpected exercise and may cause significant weight gain. A carbohydrate rich diet did benefit patients. Because of the rarity of McArdle disease, there is a need to develop international multicentre collaboration and standardised assessment protocols for future treatment trials.