Glycogen Storage Disease Type VII, Tarui disease (Glycogen storage disease type VII, Tarui disease) - Gen PFKM.

Glycogenosis type VII (GSDVII), also known as Tarui disease, is an inherited disorder caused by the inability to break down glycogen in muscle cells, interfering with the function of muscle cells. They described four types of GSDVII, which differ in their signs and symptoms and the age at which the first symptoms appear.

The classic form of GSDVII is the most common form. Signs and symptoms of classic form usually appear in childhood. This form is characterized by pain and muscle cramps, often after moderate exercise. Strenuous exercise can cause nausea and vomiting. During exercise, muscle tissue may decompose, releasing myoglobin. This protein is processed by the kidney and released into the urine. Myoglobinuria if not treated, it can damage the kidneys and cause kidney failure. Some people with the classic form of GSDVII manifest hyperuricemia because damaged kidneys can not eliminate uric acid effectively. Affected individuals may also have high levels of bilirubin in the blood that can cause jaundice. Often, individuals with the classical form have high concentrations of creatine kinase in the blood. This finding is a common indicator of muscle disease.

Meanwhile, newborns with severe childhood form of GSDVII have hypotonia at birth, leading to myopathy worsens over time. In addition, affected children have cardiomyopathy and difficulty breathing. People with this form of GSDVII usually do not survive beyond their first year of life.

In the late - onset form of GSDVII, the unique feature is, generally, myopathy. Muscle weakness appears in adulthood, although some people have difficulty with sustained exercise since childhood. General weakness affects the proximal muscles.

Hemolytic GSDVII form is characterized by hemolytic anemia, in which red blood cells break prematurely, resulting in anemia. People with hemolytic form of GSDVII have no signs or symptoms of muscle pain or weakness related to the disease.

Glycogenosis type VII (GSDVII) is due to mutations in the gene PFKM, located on the long arm of chromosome 12 (12q13.3). This gene encodes PFKM subunit of an enzyme called phosphofructokinase. This enzyme plays a role in the breakdown of glycogen. Phosphofructokinase enzyme consists of four subunits and is in a variety of tissues. In skeletal muscle, phosphofructokinase enzyme consists of subunits encoded only from PFKM gene. Phosphofructokinase is involved in the sequence of processes that break down glycogen to provide energy to muscle cells. Specifically, the enzyme converts fructose 6-phosphate to fructose 1,6 bisphosphate.

They have identified at least 20 PFKM gene mutations in people with glycogenosis type VII. These genetic changes result in PFKM encoding subunits that have little or no function. No functional subunits PFKM, no functional phosphofructokinase is formed in skeletal muscles and glycogen can not be completely decomposed, resulting in the accumulation of glycogen in muscle cells. Muscles that have no access to glycogen as a source of energy tend to weaken and in some cases, begin to break. In other tissues, other subunits that make up the enzyme phosphofructokinase likely compensate for the absence of PFKM subunits and the enzyme is able to retain some function. This compensation may help explain why other tissues are not affected by mutations in the gene PFKM.

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 VII (GSDVII), by complete PCR amplification of exons PFKM 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).