Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V)
Abstract
Background
McArdle disease (Glycogen Storage Disease type V) is caused by an absence of muscle phosphorylase leading to exercise intolerance, myoglobinuria rhabdomyolysis and acute renal failure.
Objectives
To review systematically the evidence from randomized controlled trials of pharmacological or nutritional treatments for improving exercise performance and quality of life in McArdle disease.
Search methods
We searched the Cochrane Neuromuscular Disease Group Specialised Register (17 May 2010), the Cochrane Central Register of Controlled Trials (Issue 2, 2010 in The Cochrane Library), MEDLINE (January 1966 to May 2010) and EMBASE (January 1980 to May 2010) using the search terms 'McArdle disease', 'Glycogen Storage Disease type V' and 'muscle phosphorylase deficiency'.
Selection criteria
We included randomized controlled trials (including cross‐over studies) and quasi‐randomised trials. Unblinded open trials and individual patient studies were included in the discussion. Interventions included any pharmacological agent or nutritional supplement. Primary outcome measures included any objective assessment of exercise endurance (for example aerobic capacity (VO2) max, walking speed, muscle force or power and fatigability). Secondary outcome measures included metabolic changes (such as reduced plasma creatine kinase 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
Three review authors checked the titles and abstracts identified by the search and reviewed the manuscripts. In the first review two authors (RQ and RB) independently assessed methodological quality of relevant studies and extracted data onto a specially designed form. In this update methodological quality of data was assessed by RQ and AM with comments from BS.
Main results
We identified 31 studies,13 fulfilled the criteria for inclusion. Excluded trials are included in the Discussion. The largest treatment trial included 19 subjects. There was no benefit with: D‐ribose, glucagon, verapamil, vitamin B6, branched chain amino acids, dantrolene sodium, and high dose creatine. Minimal benefit was found with low dose creatine and ramipril only for patients with a polymorphism known as the D/D angiotensin converting enzyme (ACE) phenotype. A carbohydrate‐rich diet resulted in better exercise performance compared with a protein‐rich diet. Two studies of oral sucrose given at different times and in different amounts before exercise showed an improvement in exercise performance.
Authors' conclusions
Although there was low quality evidence of improvement in some parameters with creatine, oral sucrose, ramipril and a carbohydrate rich diet, none was sufficiently strong to indicate significant clinical benefit.
PICOs
Plain language summary
Pharmacological and nutritional treatment for McArdle disease
McArdle Disease (also known as glycogen storage disease type V) is a disorder affecting muscle metabolism and is caused by the absence of an enzyme called muscle phosphorylase. This causes an inability to break down glycogen 'fuel' stores. The condition leads to pain and fatigue with strenuous exercise. Sometimes severe muscle damage may develop and occasionally this results in acute reversible kidney failure. No benefit was found with the following treatments: D‐ribose, glucagon, verapamil, vitamin B6, oral branched chain amino acids, dantrolene sodium, high dose creatine and ramipril. Minimal benefit was found with low dose creatine and ramipril for patients who also have the D/D angiotensin converting enzyme (ACE) phenotype.Taking low dose creatine supplements has a minor benefit in improving exercise tolerance in a small number of people with the condition. Taking a sugary drink before planned strenuous exercise can improve performance but this treatment is not practical for day‐to‐day living. A diet rich in carbohydrate may be superior to a diet rich in protein but this evidence is based upon only a small number of participants.
