Glycogenosis Type X, phosphoglycerate mutase deficiency (Glycogen storage disease X, Phosphoglycerate mutase deficiency) - Gen PGAM2.

Mutase deficiency (also called glycogenosis type X), is a disorder that primarily affects skeletal muscles. Signs and symptoms of this disorder begin in childhood or adolescence and may include muscle pain or cramps after strenuous physical activity and recurrent episodes of myoglobinuria. Myoglobinuria occurs when muscle tissue breaks down and releases abnormally myoglobin, which is processed by the kidneys and excreted in the urine. If left untreated, myoglobinuria can lead to kidney failure. In some cases deficient mutase, the tubular aggregates seen in the muscle fibers. However, it is unclear how these tubular aggregates are associated with signs and symptoms of the disease.

This process is due to changes in the PGAM2 gene, located on the short arm of chromosome 7 (7p13-p12). This gene encodes an enzyme called phosphoglycerate mutase. Version mutase encoded from this gene is found predominantly in skeletal muscle cells. Another version of this enzyme, encoded from a different gene, found in many other cells and tissues. The mutase is involved in the process of glycolysis. Mutase helps carry out a chemical reaction that converts 3-phosphoglycerate molecule, which is produced during the decomposition of glucose, to 2-phosphoglycerate molecule.

They have identified at least five mutations in the gene that cause PGAM2 mutase deficiency. The most common of these mutations (Trp78Ter or W78x) replaces the amino acid tryptophan by a signal early stop encoding phosphoglycerate mutase. This mutation leads to an abnormally short coding, non - functional version of the enzyme. Other mutations change individual amino acids in mutase. Mutations in the gene PGAM2 greatly reduce mutase activity, which interrupts energy production in skeletal muscle cells. This defect underlying muscle cramps, muscle breakdown and related signs and symptoms that occur after strenuous exercise in affected individuals.

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. However, people who carry an altered copy of the gene PGAM2 may have some of the characteristics of mutase deficiency, including muscle cramps and episodes of exercise - induced myoglobinuria.

Tests in IVAMI: in IVAMI perform detection of mutations associated with deficiency mutase, by complete PCR amplification of exons PGAM2 gene, 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).