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Genetics Home Reference: your guide to understanding genetic conditions
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Ataxia neuropathy spectrum

Reviewed June 2011

What is ataxia neuropathy spectrum?

Ataxia neuropathy spectrum is part of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. Ataxia neuropathy spectrum now includes the conditions previously called mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO).

As the name implies, people with ataxia neuropathy spectrum typically have problems with coordination and balance (ataxia) and disturbances in nerve function (neuropathy). The neuropathy can be classified as sensory, motor, or a combination of the two (mixed). Sensory neuropathy causes numbness, tingling, or pain in the arms and legs, and motor neuropathy refers to disturbance in the nerves used for muscle movement.

Most people with ataxia neuropathy spectrum also have severe brain dysfunction (encephalopathy) and seizures. Some affected individuals have weakness of the external muscles of the eye (ophthalmoplegia), which leads to drooping eyelids (ptosis). Other signs and symptoms can include involuntary muscle twitches (myoclonus), liver disease, depression, migraine headaches, or blindness.

How common is ataxia neuropathy spectrum?

The prevalence of ataxia neuropathy spectrum is unknown.

What genes are related to ataxia neuropathy spectrum?

Ataxia neuropathy spectrum is caused by mutations in the POLG gene or, rarely, the C10orf2 gene.

The POLG gene provides instructions for making one part, the alpha subunit, of a protein called polymerase gamma (pol γ). The C10orf2 gene provides instructions for making a protein called Twinkle. Pol γ and Twinkle function in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. Pol γ and Twinkle are both integral to the process of DNA replication by which new copies of mtDNA are produced.

Mutated pol γ or mutated Twinkle reduce mtDNA replication. Although the mechanisms are unknown, mutations in the POLG gene often result in fewer copies of mtDNA (mtDNA depletion), and mutations in the C10orf2 gene often result in deletions of large regions of mtDNA (mtDNA deletion). MtDNA depletion or deletion occurs most commonly in muscle, brain, or liver cells. MtDNA depletion causes a decrease in cellular energy, which could account for the signs and symptoms of ataxia neuropathy spectrum. It is unclear what role mtDNA deletions play in the signs and symptoms of the condition.

Related Gene(s)

Changes in these genes are associated with ataxia neuropathy spectrum.

  • C10orf2
  • POLG

How do people inherit ataxia neuropathy spectrum?

Ataxia neuropathy spectrum can have different inheritance patterns depending on the associated gene.

Mutations in the POLG gene cause a form of the condition that 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.

Mutations in the C10orf2 gene cause a form of the condition that is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Where can I find information about diagnosis or management of ataxia neuropathy spectrum?

These resources address the diagnosis or management of ataxia neuropathy spectrum and may include treatment providers.

  • Gene Review: POLG-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK26471)
  • Genetic Testing Registry: Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1843851)
  • National Ataxia Foundation: Gene Testing for Hereditary Ataxia (http://www.ataxia.org/pdf/Gene_Testing_for_Hereditary_Ataxia.pdf)
  • United Mitochondrial Disease Foundation: Diagnosis of Mitochondrial Disease (http://www.umdf.org/site/c.otJVJ7MMIqE/b.5692885/k.E71C/Getting_a_Diagnosis.htm)

You might also find information on the diagnosis or management of ataxia neuropathy spectrum in Educational resources (http://www.ghr.nlm.nih.gov/condition/ataxia-neuropathy-spectrum/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/ataxia-neuropathy-spectrum/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 ataxia neuropathy spectrum?

You may find the following resources about ataxia neuropathy spectrum 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 ataxia neuropathy spectrum?

  • ANS
  • MIRAS
  • mitochondrial recessive ataxia syndrome
  • SANDO
  • sensory ataxia neuropathy dysarthria and ophthalmoplegia

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 ataxia neuropathy spectrum?

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

What glossary definitions help with understanding ataxia neuropathy spectrum?

ANS ; ataxia ; autosomal ; autosomal dominant ; autosomal recessive ; cell ; deletion ; depletion ; depression ; DNA ; DNA replication ; dysarthria ; encephalopathy ; gene ; inheritance ; inherited ; involuntary ; migraine ; mitochondria ; motor ; myoclonus ; neuropathy ; ophthalmoplegia ; oxygen ; prevalence ; protein ; ptosis ; recessive ; sensory neuropathy ; spectrum ; subunit ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Chan SS, Longley MJ, Copeland WC. The common A467T mutation in the human mitochondrial DNA polymerase (POLG) compromises catalytic efficiency and interaction with the accessory subunit. J Biol Chem. 2005 Sep 9;280(36):31341-6. Epub 2005 Jul 16. (http://www.ncbi.nlm.nih.gov/pubmed/16024923?dopt=Abstract)
  • Gene Review: POLG-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK26471)
  • Hudson G, Deschauer M, Busse K, Zierz S, Chinnery PF. Sensory ataxic neuropathy due to a novel C10Orf2 mutation with probable germline mosaicism. Neurology. 2005 Jan 25;64(2):371-3. (http://www.ncbi.nlm.nih.gov/pubmed/15668446?dopt=Abstract)
  • Milone M, Massie R. Polymerase gamma 1 mutations: clinical correlations. Neurologist. 2010 Mar;16(2):84-91. doi: 10.1097/NRL.0b013e3181c78a89. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20220442?dopt=Abstract)
  • Moraes CT, Shanske S, Tritschler HJ, Aprille JR, Andreetta F, Bonilla E, Schon EA, DiMauro S. mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases. Am J Hum Genet. 1991 Mar;48(3):492-501. (http://www.ncbi.nlm.nih.gov/pubmed/1998336?dopt=Abstract)
  • Rocher C, Taanman JW, Pierron D, Faustin B, Benard G, Rossignol R, Malgat M, Pedespan L, Letellier T. Influence of mitochondrial DNA level on cellular energy metabolism: implications for mitochondrial diseases. J Bioenerg Biomembr. 2008 Apr;40(2):59-67. doi: 10.1007/s10863-008-9130-5. Epub 2008 Apr 16. (http://www.ncbi.nlm.nih.gov/pubmed/18415670?dopt=Abstract)
  • Stumpf JD, Copeland WC. Mitochondrial DNA replication and disease: insights from DNA polymerase γ mutations. Cell Mol Life Sci. 2011 Jan;68(2):219-33. doi: 10.1007/s00018-010-0530-4. Epub 2010 Oct 8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20927567?dopt=Abstract)
  • Van Goethem G, Martin JJ, Dermaut B, Löfgren A, Wibail A, Ververken D, Tack P, Dehaene I, Van Zandijcke M, Moonen M, Ceuterick C, De Jonghe P, Van Broeckhoven C. Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. Neuromuscul Disord. 2003 Feb;13(2):133-42. (http://www.ncbi.nlm.nih.gov/pubmed/12565911?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: June 2011
Published: September 29, 2014