Mcardle's Glycogen Storage Disease

Synonyms: Glycogen Storage Disease Type V; Myophosphorylase deficiency; Muscle glycogen phosphorylase deficiency; PYGM deficiency.

First described by McArdle in 1951, glycogen storage disease type V is an autosomal recessive disease, with heterozygotes usually not manifesting clinical features of the disease. The cause is myophosphorylase deficiency. The gene for myophosphorylase (PGYM) is on chromosome 11, and 33 distinct mutations have been identified in patients. Mutations are spread throughout the gene and there is no clear genotype:phenotype correlation.¹

Very rare disease. The overall incidence of all glycogen storage diseases is in the order of 2.3 children per 100,000 births per year.²

• The majority of patients with McArdle disease present in the second or third decade of life.

Symptoms

• Diagnosis is suggested by the history.
• Initial symptoms are cramps, fatigue, and pain after exercise.
• Because severity depends on enzyme activity, individual presentation is unique.
• Some adults develop a progressive proximal weakness.
• Some adults develop a fixed motor weakness.
• The disorder has a unique "second-wind" phenomenon.³ If a patient nearing fatigue slows exercise to a tolerable level, a point exists at which exercise may be increased again without previous symptoms.
• Burgundy-coloured urine: thought to be caused by rhabdomyolysis after intense exercise.

Signs

• Clinical findings may be absent on physical examination. Muscle strength and reflexes may be normal.
• In later adult life, persistent weakness and muscle wasting may be present.
• Ischaemic forearm test: this is a traditional test but is painful and non-ischaemic exercise tests are now preferred.⁴

• Glucose intolerance
• Glucose-6-phosphatase deficiency
• Glucose-6-phosphate dehydrogenase deficiency
• Other glycogen storage diseases.
• Liver failure
• Hypoglycaemia

• Creatine kinase levels are elevated in more than 90% of patients with McArdle disease.
• Hypoglycaemia may be found and fasting glucose testing is indicated. Elevated serum creatine kinase at rest. No increase in lactic acid following exercise.
• Urine studies are indicated because myoglobinuria may occur in some patients. Myoglobinuria is found in 50% of patients after exercise.
• Hepatic failure occurs in some patients and liver function tests should be monitored.
• Biochemical assay is required for definitive diagnosis. Phosphorylase reaction is absent.
• Electromyography: about 50% of patients may have non-specific myopathic changes. Some patients have signs of increased muscle irritability.
• Muscle biopsy: McArdle's disease is genetically heterogeneous. However, in about 90% of patients, the diagnosis of McArdle's disease can be made from a patient's leucocytes, thus avoiding the need for muscle biopsy.⁵

• No specific treatment exists.
• High-protein diet may increase exercise tolerance but is controversial. Aerobic exercise is beneficial.¹ Avoidance of intense physical activity usually ameliorates symptoms.
• Ingestion of oral sucrose immediately prior to exercise reduces perceived ratings of exertion and heart rate and improves exercise tolerance. This treatment will not influence sustained or unexpected exercise and may cause significant weight gain.⁶

Severe myoglobinuria may lead to acute renal failure.⁷

McArdle disease is a chronic but relatively benign disorder, except for possible renal failure as a complication of myoglobinuria.⁷ Progression to chronic renal disease has not been described.

Genetic counselling is appropriate for all individuals with a genetic disorder.