What Is Glycogen Storage Disease Type V (GSD V)?

Glycogen storage disease type V (GSD V) is a rare illness that results in fatigue and muscle pain during exercise. Also known as McArdle disease, it mainly affects skeletal muscles.

This condition is caused by a lack of the enzyme myophosphorylase. This enzyme promotes the breakdown of glycogen into glucose during intense exercise, such as jogging. Without enough of the enzyme, the muscles can't change glycogen into glucose.

While symptoms occur at the start of movement, the pain is often eased by rest. After this, the affected person can usually resume motion without pain.

Symptoms and problems vary from absent to severe. The most common problems involve damage to the muscles or kidneys. There is no treatment for this disease, though certain diet and workout plans can help manage it.

This article describes GSD V symptoms, causes, diagnosis, and treatment.

Types of GSD V

GSD V is one of at least 16 recognized varieties of glycogen storage diseases. These disorders interfere with the processes needed to change glycogen to glucose.

There are two types of GSD V:

• Classic
• Late-onset
• Fatal infantile variant

Symptoms

Symptoms of GSD V can range from nonexistent to extreme. Disease severity can vary significantly among affected people.

While most people report their first symptoms during their teenage years or early 20s, symptoms of this disease can occur at any time between infancy and late in life.

The most common symptom of this disease involves exercise intolerance. This includes the onset of the following symptoms during the first few minutes of activities that require intense movement or strength:

• Fatigue
• Muscle pain
• Muscle cramps
• Poor stamina
• Muscle contractions

Symptoms usually subside when you take a rest period of about 10 minutes at the first sign of fatigue or muscle pain. This short break allows your body to seek other fuel sources in the absence of enough glucose. About 90% of affected people benefit from a phenomenon unique to this condition, called a "second wind," which allows you to resume exercise with little to no symptoms.

Exercising for long periods of time can result in rhabdomyolysis, a condition in which the body breaks down muscle tissue to gain energy that it lacks.

Symptoms of rhabdomyolysis include:

• Extreme muscle pain
• Weakness
• Swelling
• Muscle stiffness

Kidney failure can also occur as a result of prolonged myoglobinuria, which affects about 50% of people with this disease. This occurs when the myoglobin, or red muscle protein, that results from rhabdomyolysis is released through the kidneys. Myoglobinuria causes red or brown urine.

Causes

GSD V is a genetic disease that is caused by changes in the PYGM (glycogen phosphorylase, muscle form) gene. It is passed from parent to child in an autosomal recessive pattern. This means that both parents must pass down the same defective gene for the child to develop a disorder.

The child of two parents with the recessive defective gene has a 25% chance of getting the disease and a 50% of having a child who is a carrier. When a parent has an autosomal recessive trait, they don't have symptoms and usually don't know they have the condition.

Diagnosis

You must visit a healthcare provider to get a definitive diagnosis of GSD V. A physical examination and family history help your provider assess your symptoms.

The primary method of diagnosis is through molecular analysis of DNA in blood samples. This type of genetic testing is the most common technique for screening the gene mutations related to GSD V.

The following diagnostic tests can also be used to determine characteristics common to this condition:

• Forearm ischemic exercise test (FIET) (tool that can detect metabolic disorders of muscles)
• Blood test to measure levels of creatine kinase, a muscle enzyme
• Muscle biopsy (removing and testing a sample of muscle tissue) to determine deficiency of myophosphorylase enzyme or glycogen buildup
• Electromyography to identify abnormal muscle activity
• Functional tests (12-minute walk test or static cycle test) to test for presence of the second wind phenomenon
• Urinalysis (analyzing urine) to measure levels of myoglobin
  

Treatment

There is no single treatment or cure for GSD V. Management of the disease aims to provide therapies to reduce symptoms and prevent complications. The most common approaches involve a combination of diet and activity modifications.

While your healthcare provider can advise the changes necessary to address your unique condition and symptoms, common treatments for this disease include:

• A high carbohydrate diet to improve work capacity and exercise tolerance
• Regular moderate aerobic activity keeping the heart rate at 60%–70% of maximum using a heart rate monitor, to simulate a permanent second wind phenomenon
• Avoidance of intense isometric, maximal aerobic exercise, and anaerobic exercise, which are common triggers of cramps, rhabdomyolysis, and myoglobinuria
• Avoidance of a sedentary (inactive) lifestyle, which can lead to deconditioning
  

Prognosis

The prognosis for people with GSD V is generally good when patients follow diet and exercise recommendations. Most people affected by this disease lead a normal life.

While symptoms are usually limited to periods of exercise, a minority of those affected experience weakness in daily life. Some people have symptoms that worsen over time.

While muscle weakness stabilizes in about 30% of affected people, it can worsen over time in others.

Following your healthcare provider's lifestyle guidance can help you avoid severe rhabdomyolysis. Without disease management, you increase your risk of myoglobinuria, which can lead to kidney failure, a potentially life-threatening condition.

Fatal infantile McArdle syndrome, which is a severe and rapidly progressive form of this disease, carries a grave prognosis. The condition includes symptoms of hypotonia (decreased muscle tone), generalized muscle weakness, and progressive respiratory insufficiency in infants.

Coping

Managing GSD V requires lifelong monitoring and follow-up with your healthcare providers.

Your disease management will require working with a team of multidisciplinary specialists that may include the following healthcare professionals:

• Primary healthcare provider
• Metabolic specialist
• Metabolic dietitian
• Nephrologist (medical doctor specializing in kidney diseases)
• Physical therapist
• Genetic counselor
• Psychologist

If you or your child is diagnosed with this condition, patient education is key to understanding the types of exercises that should be avoided to prevent complications. If you are the parent of a child affected by this disease, you will have to work with your child to modify their physical activity. You will also have to communicate your child's needs to other caregivers.

Summary

GSD V, also known as McArdle disease, causes fatigue and muscle pain during extreme movement. This condition is caused by the lack of a certain enzyme needed to change glycogen into glucose within the muscles.

Without enough glucose, muscle pain and cramping occur. Many people find relief by waiting about 10 minutes until a second wind allows them to resume motion without pain.

The organs most commonly damaged by this disease are the skeletal muscles and kidneys. In extreme cases, kidney failure can occur.

While there is no cure for this condition currently, managed diet and workout plans can improve results. People with this disease must avoid intense, prolonged movement to prevent health problems and live normally.

A Word From Verywell

Living with GSD V or any other rare disease can be isolating. Seek out groups online that include people affected by this disease. Interacting with others who have this condition can provide the support and strategies you need to meet the challenges of this disease.

While any glycogen storage disease is a challenging diagnosis, the good news is that the prognosis for most people with this condition is relatively good. It can usually be managed by following the diet and exercise plans advised by your healthcare provider. Doing so can improve your prognosis and allow you to live a normal life with a lower risk of disease complications.