Glycogen storage disease type 5

Glycogenosis type 5, also known as McArdle disease, belongs to the group of glycogen storage diseases and follows an autosomal recessive mode of inheritance.

Glycogenosis type 5 is characterized by exercise intolerance and is caused by mutations in the PYGM gene, resulting in a deficit in the enzyme encoded by this gene, muscle phosphorylase or myophosphorylase. This enzyme is involved in the degradation of glycogen in skeletal muscle.

The prevalence of McArdle's disease is estimated at 1 -2 cases per 200,000 people.

Symptoms usually begin in childhood or in young adults. Patients present with exercise intolerance, myalgia, cramps, contractures, fatigue and muscle weakness. An increase in serum creatine kinase occurs in most patients.

Persistent skeletal muscle activity despite symptoms, intense exertion, anaerobic activity, weight lifting, weight carrying and sustained muscle contraction can cause episodes of rhabdomyolysis or breakdown of muscle tissue as a result of damage to muscle cells. This releases large amounts of myoglobin into the bloodstream which can lead to acute renal failure.

In many patients a recovery phenomenon is observed with relief of myalgia and muscle fatigue after a few minutes of rest.

McArdle's disease is considered a "pure" myopathy, i.e. it rarely affects tissues other than skeletal muscle. In recent years it has been observed that certain patients may develop retinal dystrophy and hypothyroidism.

To date, there is no treatment to restore myophosphorylase activity. Management of patients focuses on controlled aerobic training of moderate intensity in order to develop the oxidative capacity of the muscles and increase cardiorespiratory fitness, ensuring that sufficient blood glucose is available to the muscles. In McArdle's patients, glucose levels can be maintained in two ways, with a diet rich in complex carbohydrates and low in fat and with the scheduled intake of simple sugars (30-40g of glucose, fructose or sucrose) 5 minutes before exercise.

The prognosis is favorable when massive rhabdomyolysis is avoided. However, given that the increase of myoglobin in the blood can lead to severe renal failure, the evolution of the pathology must be properly monitored.