Glycogen storage disease type V

The McArdle 's disease ( McArdle's myopathy, McArdle 's disease, McArdle 's syndrome), also known as glycogen storage disease type V ( GSD5 ), is a glycogen storage disease, which is 1951 by the pediatrician Brian McArdle ( 1911-2002 ) was first described. Basis is a defect occurring in skeletal muscle isoform of the enzyme glycogen phosphorylase, which is also referred to as Myophosphorylase. The disease is inherited as an autosomal recessive trait.

Pathogenesis

In patients with this disease there is an energy recovery disorder. The storage and availability of the energy source glucose in the muscles is the polysaccharide glycogen. The function of the Myophosphorylase is to mobilize from the glycogen glucose residues, and make it available within the glycolysis or the oxidative TCA cycle for energy production. This Entspeicherung glucose disrupted by an enzyme defect, there is an accumulation of glycogen and, in particular, under heavy load, to a lower energy supply to the muscle.

Symptoms

Symptoms already in young adulthood. Characteristic features are a diminished capacity of the muscles ( myasthenia ), muscle pain (myalgia ), muscle stiffness and spasms. The complaints arise either for short-term severe stress on the muscles ( strength training, carrying heavy loads), or less serious, but prolonged stress ( running, walking ). Moderate muscle strain, however, can be maintained over a relatively long period of time without any significant discomfort. Many sufferers report that a pause after the first appearance of symptoms leads to a good and then complaining poor muscle strength. This effect is characteristic of and is referred to in English as a second wind Phenomenon.

Some patients also report on a dark-colored urine after exercise. This is a collection of muscle breakdown products in the urine ( myoglobinuria ) as a result of increased muscle damage (rhabdomyolysis ), since the tissue integrity of the muscles can not be sustained by the lack of energy. In severe cases, myoglobinuria leading to acute renal failure.

Diagnosis

As a non-specific signs of muscle injury, the blood concentration of creatine kinase (CK ) is increased especially after physical stress. Furthermore, there are increases in ammonia and uric acid. Strains under anaerobic conditions do not lead to an increase of lactate in the blood, but to a strong increase of the ammonia. This may indicate a fault in the breakdown of glycogen in the muscle cell, but is not a pathognomonic sign for McArdle's disease, because similar findings constellations are also found in other enzymatic disorders of glycogen.

Muscle biopsy is histologically in PAS staining an increased glycogen storage in the muscle fibers detectable. There is often a selective atrophy of type I muscle fibers. Subsarkolemmale vacuoles and peculiar disturbances of intermyofibrillären network in the NADH staining, the so-called linearizations are considered typical. Enzymhistochemisch the activity of phosphorylase is significantly reduced or eliminated. The diagnosis may optionally be supported by molecular genetic studies to detect a mutation PGYM on.

The McArdle 's disease can be diagnosed in combination with a moderate muscle strain test even without the surgery a -r muscle biopsy using the non-invasive 31Phosphor - magnetic resonance spectroscopy ( 31P -MRS). The 31P -MRS determines the high-energy phosphates and intracellular pH during exercise in muscle. A healthy muscle with an intact glycolytic metabolism is parallel to the breakdown of phosphocreatine (PKR ) as much lactate that after a short initial pH increase a drop in the intracellular pH can be seen from the spectra. The glycolytic ATP formation is delayed in healthy subjects during a constant load, the degradation rate of PKR. The concentration of ATP remains constant during exercise in healthy subjects. The relaxation rate of PKR after a load reflects the oxygen-dependent metabolism in the muscle, which is dependent in healthy subjects from the training condition. In patients with Muskelglykogenosen lactate formation is missing. Therefore, the pH value increases in the course of muscle contraction as a result of degradation of PKR continuously up to values ​​of 7.3 at. The rate of PKR degradation not delayed but increases during the course of a constant load very often even on. In most cases, then decreases the concentration of ATP in the muscle. The recovery of PKR after a load is delayed in patients with McArdle's disease often pathological. A deficiency of enzymes of glycolysis is different from a primary deficiency of glycogen breakdown in the accumulation of sugar phosphates during exercise.

Therapy

A causal therapy is not yet available. For permanent weakness of the muscles physiotherapy may be useful. However, in the foreground stands the test of dietary affected by the specific supply of glucose or fructose shortly before or during exercise. By endurance training below the anaerobic threshold, a significant improvement in the performance can be achieved. Low-dose treatment with creatine went in a small clinical study with a significant improvement in muscular symptoms compared to placebo accompanied. The life expectancy is not significantly affected.

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