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. This is an update of a review first published in 2004.Objectives To review systematically the evidence from randomised controlled trials (RCTs) 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 Specialized Register, CENTRAL, MEDLINE and EMBASE on 11 August 2014.Selection criteria We included RCTs (including cross-over studies) and quasi-RCTs. We included unblinded open trials and individual patient studies 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. Two review authors independently assessed the risk of bias of relevant studies, with comments from a third author. Two authors extracted data onto a specially designed form.Main results We identified 31 studies, and 13 fulfilled the criteria for inclusion. We described trials that were not eligible for the review in the Discussion. The included studies involved a total of 85 participants, but the number in each individual trial was small; the largest treatment trial included 19 participants and the smallest study included only one participant. There was no benefit with:
D-ribose,
glucagon,
verapamil,
vitamin B6,
branched chain amino acids,
dantrolene sodium, and high-dose
creatine. Minimal subjective benefit was found with low dose
creatine and
ramipril only for patients with a polymorphism known as the D/Dangiotens in 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. Four studies reported adverse effects. Oral
ribose caused diarrhoea and symptoms suggestive of hypoglycaemia including
light-headedness and hunger. In one study,
branched chain amino acids caused a deterioration of functional outcomes.
Dantrolene was reported to cause a number of adverse effects including tiredness,
somnolence,
dizziness and
muscle weakness. Low dose
creatine (60 mg/kg/day) did not cause side-effects but high-dose
creatine (150 mg/kg/day) worsened the symptoms of
myalgia.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.