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Myopathy with deficiency of iron-sulfur cluster assembly enzyme is an inherited disorder that primarily affects muscles used for movement (skeletal muscles). This condition does not usually affect other types of muscle, such as the heart (cardiac) muscle.
From early childhood, affected individuals experience extreme fatigue in response to physical activity (exercise intolerance). Mild exertion results in a rapid heartbeat (tachycardia), shortness of breath, and muscle weakness and pain. However, people with this condition typically have normal muscle strength when they are at rest.
Prolonged or recurrent physical activity causes more severe signs and symptoms, including a breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, in some cases leading to life-threatening kidney failure.
In most affected individuals, the muscle problems associated with this condition do not worsen with time. However, at least two people with a severe variant of this disorder have experienced progressive muscle weakness and wasting starting in childhood.
This condition has been reported in several families of northern Swedish ancestry.
Myopathy with deficiency of iron-sulfur cluster assembly enzyme is caused by mutations in the ISCU gene. This gene provides instructions for making a protein called the iron-sulfur cluster assembly enzyme. As its name suggests, this enzyme is involved in the formation of clusters of iron and sulfur atoms (Fe-S clusters). These clusters are critical for the function of many different proteins, including those needed for DNA repair and the regulation of iron levels. Proteins containing Fe-S clusters are also necessary for energy production within mitochondria, which are the cell structures that convert the energy from food into a form that cells can use.
Mutations in the ISCU gene severely limit the amount of iron-sulfur cluster assembly enzyme that is made in cells. A shortage of this enzyme prevents the normal production of proteins that contain Fe-S clusters, which disrupts a variety of cellular activities. A reduction in the amount of iron-sulfur cluster assembly enzyme is particularly damaging to skeletal muscle cells. Within the mitochondria of these cells, a lack of this enzyme causes problems with energy production and an overload of iron. These defects lead to exercise intolerance and the other features of myopathy with deficiency of iron-sulfur cluster assembly enzyme.
Changes in this gene are associated with myopathy with deficiency of iron-sulfur cluster assembly enzyme.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
These resources address the diagnosis or management of myopathy with deficiency of iron-sulfur cluster assembly enzyme and may include treatment providers.
You might also find information on the diagnosis or management of myopathy with deficiency of iron-sulfur cluster assembly enzyme in Educational resources (http://www.ghr.nlm.nih.gov/condition/myopathy-with-deficiency-of-iron-sulfur-cluster-assembly-enzyme/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/myopathy-with-deficiency-of-iron-sulfur-cluster-assembly-enzyme/show/Patient+support).
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
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You may find the following resources about myopathy with deficiency of iron-sulfur cluster assembly enzyme helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
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Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
acidosis ; autosomal ; autosomal recessive ; breakdown ; cardiac ; cell ; deficiency ; dehydrogenase ; DNA ; DNA repair ; enzyme ; gene ; hereditary ; inherited ; iron ; kidney ; lactic acidosis ; mitochondria ; muscle cells ; myoglobin ; myoglobinuria ; protein ; recessive ; rhabdomyolysis ; skeletal muscle ; tachycardia ; tissue ; wasting
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
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