Myopathy deficient enzymes couplers iron-sulfur (Myopathy With deficiency of iron-sulfur cluster assembly enzyme) - Gen ISCU.

Myopathy deficient enzymes couplers iron and sulfur is a hereditary disease which primarily affects skeletal muscles. This alteration does not usually affect other muscles such as the heart.

Signs and symptoms of the disease appear in early childhood as a result of moderate physical activity, including extreme fatigue in response to physical activity, rapid heartbeat, difficulty breathing, muscle weakness and pain. However, those affected typically have normal muscle strength when they are at rest. Prolonged or recurrent physical activity causes severe symptoms and signs, including rhabdomyolysis and myoglobinuria. This protein can also damage the kidneys, leading in some cases to a potentially fatal renal failure. Although there have been isolated cases in which muscle weakness is progressive since childhood generally associated muscle problems do not worsen over time.

This process is due to mutations in the gene ISCU, located on the long arm of chromosome 12 (12q24.1). This gene encodes a protein involved in the formation of groups of iron-sulfur (Fe - S clusters), critical for the function of many different proteins, including those needed for DNA repair and regulation of iron concentrations. Proteins containing Fe -S are also necessary for energy production within mitochondria.

They have identified at least two mutations in the gene ISCU in people with myopathy deficient enzymes couplers iron and sulfur. The most common mutation, IVS5 + 382G> C, alters the way in which the gene encoding the enzyme. Most affected individuals have this mutation in both copies of the gene in each cell ISCU. The other mutation, which has been identified in a family, replacing the amino acid glycine amino acid glutamate at position 50 (Gly50Glu or G50E). Affected individuals in this family have had the G50E mutation in one copy of the gene in each cell and the mutation IVS5 + 382G> C in the other copy of the gene. This combination of mutations causes a severe form of the disease that is characterized by progressive muscle weakness and atrophy. Mutations in the gene significantly limit the amount of encoded protein in the cells. In the absence of this enzyme the normal production of proteins containing groups Fe- S, interrupting a variety of cellular activities, particularly damaging to the skeletal muscle cells is altered. Within the mitochondria of these cells, the lack of this enzyme causes problems with energy production and iron overload. These defects lead to exercise intolerance and other features of the disease.

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 myopathy deficient enzymes couplers iron and sulfur, by the complete PCR amplification of the exons of the gene ISCU, 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).