Disease Directory McArdle Disease
Neuromuscular

McArdle Disease

Also known as: GSD type V, glycogen storage disease type 5, myophosphorylase deficiency

Prevalence

1 in 100,000 to 1 in 167,000

Onset

Childhood (symptoms typically apparent by age 10, though diagnosis often delayed)

Type

Autosomal recessive

Gene

PYGM

About McArdle Disease

McArdle Disease is caused by bi-allelic mutations in the PYGM gene, resulting in complete absence of myophosphorylase — the muscle isoform of glycogen phosphorylase — which blocks glycogen breakdown in skeletal muscle during exercise. This leads to exercise intolerance, myalgia, and rhabdomyolysis, but the pathognomonic 'second wind' phenomenon — a spontaneous improvement in exercise capacity after 8–10 minutes — distinguishes it from other exercise-induced myopathies. Severe rhabdomyolysis can cause acute kidney injury.

Common Clinical Features

Exercise intolerance, myalgia, and early fatigue during exertion Second wind phenomenon (recovery of exercise tolerance after 8–10 minutes) Rhabdomyolysis with dark (cola-coloured) urine after intense exercise Muscle cramps and contractures during exercise Persistent proximal weakness in older patients Markedly elevated serum creatine kinase (even at rest) Myoglobinuria and risk of acute renal failure

Clinical Trial Eligibility Tips

What to know before applying to McArdle Disease trials.

Forearm ischaemic (or non-ischaemic) exercise test showing absent venous lactate rise with normal ammonia rise is diagnostic and frequently documented as part of eligibility screening

Genetic confirmation of bi-allelic PYGM mutations is required; the common p.R50X variant is found in approximately 60% of European alleles and can be rapidly screened

Cardiopulmonary exercise testing (CPET) and peak VO2 are increasingly used as primary endpoints; a structured exercise test with a physiologist prior to trial application is highly recommended

Patient Resources

Patient Organization

Association for Glycogen Storage Disease

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Natural History Registry

IamGSD Registry

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Orphanet

European reference resource for rare diseases (ORPHA:368)

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NORD

National Organization for Rare Disorders

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Find recruiting McArdle Disease trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for McArdle Disease. Updated daily.

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