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Genetics Home Reference: your guide to understanding genetic conditions
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Myopathy with deficiency of iron-sulfur cluster assembly enzyme

Reviewed November 2009

What is myopathy with deficiency of iron-sulfur cluster assembly enzyme?

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.

How common is myopathy with deficiency of iron-sulfur cluster assembly enzyme?

This condition has been reported in several families of northern Swedish ancestry.

What genes are related to myopathy with deficiency of iron-sulfur cluster assembly enzyme?

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.

Related Gene(s)

Changes in this gene are associated with myopathy with deficiency of iron-sulfur cluster assembly enzyme.

  • ISCU

How do people inherit 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.

Where can I find information about diagnosis or management of myopathy with deficiency of iron-sulfur cluster assembly enzyme?

These resources address the diagnosis or management of myopathy with deficiency of iron-sulfur cluster assembly enzyme and may include treatment providers.

  • Gene Review: Myopathy with Deficiency of ISCU (http://www.ncbi.nlm.nih.gov/books/NBK5299)
  • Genetic Testing Registry: Myopathy with lactic acidosis, hereditary (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1850718)
  • MedlinePlus Encyclopedia: Rhabdomyolysis (http://www.nlm.nih.gov/medlineplus/ency/article/000473.htm)

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).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about myopathy with deficiency of iron-sulfur cluster assembly enzyme?

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.

What other names do people use for myopathy with deficiency of iron-sulfur cluster assembly enzyme?

  • hereditary myopathy with lactic acidosis
  • HML
  • iron-sulfur cluster deficiency myopathy
  • myoglobinuria due to abnormal glycolysis
  • myopathy with deficiency of ISCU
  • myopathy with deficiency of succinate dehydrogenase and aconitase
  • myopathy with exercise intolerance, Swedish type

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about myopathy with deficiency of iron-sulfur cluster assembly enzyme?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding myopathy with deficiency of iron-sulfur cluster assembly enzyme?

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).

References

  • Drugge U, Holmberg M, Holmgren G, Almay BG, Linderholm H. Hereditary myopathy with lactic acidosis, succinate dehydrogenase and aconitase deficiency in northern Sweden: a genealogical study. J Med Genet. 1995 May;32(5):344-7. (http://www.ncbi.nlm.nih.gov/pubmed/7616539?dopt=Abstract)
  • Gene Review: Myopathy with Deficiency of ISCU (http://www.ncbi.nlm.nih.gov/books/NBK5299)
  • Kollberg G, Tulinius M, Melberg A, Darin N, Andersen O, Holmgren D, Oldfors A, Holme E. Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy. Brain. 2009 Aug;132(Pt 8):2170-9. doi: 10.1093/brain/awp152. Epub 2009 Jun 30. (http://www.ncbi.nlm.nih.gov/pubmed/19567699?dopt=Abstract)
  • Mochel F, Knight MA, Tong WH, Hernandez D, Ayyad K, Taivassalo T, Andersen PM, Singleton A, Rouault TA, Fischbeck KH, Haller RG. Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. Am J Hum Genet. 2008 Mar;82(3):652-60. doi: 10.1016/j.ajhg.2007.12.012. Epub 2008 Feb 14. (http://www.ncbi.nlm.nih.gov/pubmed/18304497?dopt=Abstract)
  • Olsson A, Lind L, Thornell LE, Holmberg M. Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect. Hum Mol Genet. 2008 Jun 1;17(11):1666-72. doi: 10.1093/hmg/ddn057. Epub 2008 Feb 23. (http://www.ncbi.nlm.nih.gov/pubmed/18296749?dopt=Abstract)
  • Rouault TA, Tong WH. Iron-sulfur cluster biogenesis and human disease. Trends Genet. 2008 Aug;24(8):398-407. doi: 10.1016/j.tig.2008.05.008. Epub 2008 Jul 5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18606475?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2009
Published: October 27, 2014