Glycogen Storage Disease Type V, McArdle 's disease (Glycogen storage disease type V, McArdle disease) - Gen PYGM.

Glycogenosis type V (also known as GSDV disease or McArdle disease) is an inherited disorder caused by the inability to break down glycogen in muscle cells, interfering with the function of muscle cells. Signs and symptoms associated with the disease may include fatigue, muscle pain and exercise intolerance. The malaise is relieved by rest. Usually, if individuals exercise after a brief rest and wait for the pain to go away, they can resume exercise 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 those affected have rhabdomyolysis. In severe episodes, the destruction of muscle tissue releases myoglobin, which is filtered through the kidneys and released into the urine. Myoglobin causes the urine red or brown. This protein can also damage the kidneys, and an estimated half of the individuals who have myoglobinuria GSDV develop potentially fatal renal failure.

Signs and symptoms of type V glycogenosis can vary significantly affected individuals. Generally, the characteristics of this disease begin in adolescence or around age 20, but can appear at any time from infancy to adulthood. In most of those affected, muscle weakness worsens over time; however, about one - third of individuals, muscle weakness is stable.

This process is due to mutations in the gene PYGM located on the long arm of chromosome 11 (11q12-q13.2). This gene encodes an enzyme called myophosphorylase. This enzyme is one of three related enzymes called glycogen phosphorylase decomposing glycogen in the cells. Myophosphorylase found only in muscle cells, where the glycogen is broken down in a simple carbohydrate called glucose 1-phosphate. Additional steps convert glucose 1-phosphate into glucose.

Approximately 130 have been identified mutations in the gene responsible for PYGM glycogenosis type V. A mutation that is common in North American and European populations (Arg50Ter or R50X), creates a premature stop signal coding myophosphorylase, decreasing coding . Myophosphorylase deficiency affects the normal breakdown of glycogen. Other mutations severely reduce enzyme activity or change the form of the enzyme, which is folded in 3-dimensional form a. The defective enzyme can not break down glycogen. As a result, muscle cells can not produce enough energy, so that the muscles are easily fatigued. The reduction of energy production in muscle cells leads to the main features of GSDV.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with glycogen storage disease type V or McArdle disease by the complete PCR amplification of the exons of the gene PYGM, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).