Glycogen storage disease type 5

Brief summary

• Glycogen storage disease type V (also known as GSDV or McArdle disease) is an inherited disorder caused by an inability to break down a complex sugar called glycogen in muscle cells.
• A lack of glycogen breakdown interferes with the function of muscle cells.

Other Names:

• GSD 5;
• McArdle disease;
• McArdle type glycogen storage disease;
• PYGM deficiency;
• Muscle glycogen phosphorylase deficiency;
• Myophosphorylase deficiency

Epidemiology

GSDV is a rare disorder; however, its prevalence is unknown. In the Dallas-Fort Worth area of Texas, where the prevalence of GSDV has been studied, the condition is estimated to affect 1 in 100,000 individuals.

Cause

Mutations in the PYGM gene cause GSDV. The PYGM gene provides instructions for making an enzyme called myophosphorylase. This enzyme is found only in muscle cells, where it breaks down glycogen into a simpler sugar called glucose-1-phosphate. Additional steps convert glucose-1-phosphate into glucose, a simple sugar that is the main energy source for most cells. PYGM gene mutations prevent myophosphorylase from breaking down glycogen effectively. As a result, muscle cells cannot produce enough energy, so muscles become easily fatigued. Reduced energy production in muscle cells leads to the major features of GSDV.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

• People with GSDV typically experience fatigue, muscle pain, and cramps during the first few minutes of exercise (exercise intolerance). Exercise such as weight lifting or jogging usually triggers these symptoms in affected individuals. The discomfort is generally alleviated with rest. If individuals rest after brief exercise and wait for their pain to go away, they can usually resume exercising with little or no discomfort (a characteristic phenomenon known as "second wind").
• Prolonged or intense exercise can cause muscle damage in people with GSDV. About half of people with GSDV experience breakdown of muscle tissue (rhabdomyolysis). In severe episodes, the destruction of muscle tissue releases a protein called myoglobin, which is filtered through the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, and it is estimated that half of those individuals with GSDV who have myoglobinuria will develop life-threatening kidney failure.
• The signs and symptoms of GSDV can vary significantly in affected individuals. The features of this condition typically begin in a person's teens or twenties, but they can appear anytime from infancy to adulthood. In most people with GSDV, the muscle weakness worsens over time; however, in about one-third of affected individuals, the muscle weakness is stable. Some people with GSDV experience mild symptoms such as poor stamina; others do not experience any symptoms.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Exercise intolerance(Decreased ability to exercise)
• Glycogen accumulation in muscle fiber lysosomes
• Highly elevated creatine kinase

30%-79% of people have these symptoms

• Dark urine
• Exercise-induced muscle cramps(Exercise-induced muscle cramping)
• Exercise-induced myoglobinuria
• Recurrent myoglobinuria
• Rhabdomyolysis(Breakdown of skeletal muscle)

5%-29% of people have these symptoms

• Acute kidney injury
• Exercise-induced muscle stiffness(Muscle stiffness with exercise)
• Exercise-induced myalgia(Exercise-induced muscle pain)
• Exertional dyspnea
• Hypertrophic cardiomyopathy(Enlarged and thickened heart muscle)
• Postexertional malaise
• Progressive proximal muscle weakness
• Skeletal muscle atrophy(Muscle degeneration)
• Tachycardia(Fast heart rate)

1%-4% of people have these symptoms

• Chronic kidney disease
• Dysphagia(Poor swallowing)
• Elevated serum creatine kinase(Elevated blood creatine phosphokinase)
• Impaired mastication(Chewing difficulties)
• Muscle weakness(Muscular weakness)
• Myoglobinuria

Diagnosis

The diagnosis of GSDV is established in a proband with suggestive findings and by identification of biallelic PYGM (encoding glycogen phosphorylase, muscle form) pathogenic variants on molecular genetic testing or – if genetic test results are not diagnostic – by assay of muscle myophosphorylase enzyme activity.

Treatment

Although no cure for GSDV is available, affected individuals benefit from moderate-intensity aerobic training (e.g., walking or brisk walking, bicycling) to increase cardiorespiratory fitness and muscle oxidative capacity. Pre-exercise ingestion of sports drinks containing simple carbohydrates improves exercise tolerance and may protect against exercise-induced rhabdomyolysis.

NIH genetic and rare disease info

• NIH info on Glycogen storage disease type 5

Glycogen storage disease type 5 is a rare disease.

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