McArdle disease: a clinical review

Abstract

The clinical phenotype of 45 genetically confirmed McArdle patients is described.In the majority of patients (84%), the onset of symptoms was from early childhood, but diagnosis was frequently delayed until after 30 years of age. Not all patients could recognise a second wind, although it was always seen with exercise assessment. A history of myoglobinuria was not universal, and episodes of acute renal failure had occurred in a minority (11%). The condition does not appear to adversely affect pregnancy and childbirth. Clinical examination was normal in most patients, muscle hypertrophy was present in 24% and mild muscle wasting and weakness was seen only in patients over 40 years of age and was limited to shoulder girdle and axial muscles. The serum creatine kinase (CK) was elevated in all but one pregnant patient. Screening for the mutations p.Arg50X (R50X) and p.Gly205Ser (G205S) showed at least one mutated allele in 96% of Caucasian British patients, with an allele frequency of 77% for p.Arg50X in this population. A 12-minute walking test to evaluate patients is described, results demonstrated a wide spectrum of severity with the range of distance walked being 195-1980 metres, the mean distance walked was 512m suggesting significant functional impairment in most patients.

From exercise intolerance to functional improvement: the second wind phenomenon in the identification of McArdle disease

“…A carefully taken history is essential to diagnose this condition. Exercise intolerance usually starts during the first few minutes of physical activity and is described as muscle pain, discomfort, stiffness, cramps, fatigue and/or exhaustion 2,4,6,7 . It is commonly associated with dyspnoea and tachycardia.…”

“…Fixed weakness affecting the paraspinal and upper limb muscles may occur. Muscle hypertrophy can also be seen in a proportion of patients 4,6,9 . The finding of a raised serum CK in combination with exercise intolerance should raise suspicion of a metabolic myopathy.…”

“…Although the second wind phenomenon is present in all cases of McArdle disease, some patients may have difficulty in recognizing and eliciting the phenomenon in themselves during everyday physical activity 4,6 . Consequently, they may not volunteer it in the clinical history even if it is specifically asked for.…”

“…Performing an exercise test to reproduce the phenomenon in a clinic setting may not only help with the diagnostic process for McArdle disease but also be used to demonstrate the phenomenon to patients from a therapeutic perspective. There are two exercise tests that elicit the second wind phenomenon in McArdle disease, namely 12 minute walk test (12 MWT) 6 and cycle test 13 . The 12 MWT is a simple, easy, non-invasive assessment that can be performed in any clinical setting 6 .…”

“…Unfortunately, there is often a delay in diagnosing McArdle disease and affected individuals may be misdiagnosed with other disorders such as polymyositis and chronic fatigue syndrome 5,6 . The second wind phenomenon, as described in a 12 minute walking test and 15 minute cycle test, is known to be pathognomonic for McArdle disease and its identification in the clinic can aid diagnosis.…”