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Yang, C. Ataxia Neuropathy Spectrum. Encyclopedia. Available online: https://encyclopedia.pub/entry/4816 (accessed on 25 April 2024).
Yang C. Ataxia Neuropathy Spectrum. Encyclopedia. Available at: https://encyclopedia.pub/entry/4816. Accessed April 25, 2024.
Yang, Catherine. "Ataxia Neuropathy Spectrum" Encyclopedia, https://encyclopedia.pub/entry/4816 (accessed April 25, 2024).
Yang, C. (2020, December 24). Ataxia Neuropathy Spectrum. In Encyclopedia. https://encyclopedia.pub/entry/4816
Yang, Catherine. "Ataxia Neuropathy Spectrum." Encyclopedia. Web. 24 December, 2020.
Ataxia Neuropathy Spectrum
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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/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).

genetic conditions

1. Introduction

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.

2. Frequency

The prevalence of ataxia neuropathy spectrum is unknown.

3. Causes

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

The POLG gene provides instructions for making one part, the alpha subunit, of a protein called polymerase gamma (pol γ). The TWNK 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 TWNK 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.

3.1. The genes associated with Ataxia neuropathy spectrum

  • POLG
  • TWNK

4. Inheritance

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 TWNK 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.

5. Other Names for This Condition

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

References

  1. Chan SS, Longley MJ, Copeland WC. The common A467T mutation in the humanmitochondrial DNA polymerase (POLG) compromises catalytic efficiency andinteraction with the accessory subunit. J Biol Chem. 2005 Sep 9;280(36):31341-6.
  2. Cohen BH, Chinnery PF, Copeland WC. POLG-Related Disorders. 2010 Mar 16[updated 2018 Mar 1]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH,Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): Universityof Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK26471/
  3. Hudson G, Deschauer M, Busse K, Zierz S, Chinnery PF. Sensory ataxicneuropathy due to a novel C10Orf2 mutation with probable germline mosaicism.Neurology. 2005 Jan 25;64(2):371-3.
  4. Milone M, Massie R. Polymerase gamma 1 mutations: clinical correlations.Neurologist. 2010 Mar;16(2):84-91. doi: 10.1097/NRL.0b013e3181c78a89. Review.
  5. Moraes CT, Shanske S, Tritschler HJ, Aprille JR, Andreetta F, Bonilla E, SchonEA, DiMauro S. mtDNA depletion with variable tissue expression: a novel geneticabnormality in mitochondrial diseases. Am J Hum Genet. 1991 Mar;48(3):492-501.
  6. 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. 2008Apr;40(2):59-67. doi: 10.1007/s10863-008-9130-5.
  7. Stumpf JD, Copeland WC. Mitochondrial DNA replication and disease: insightsfrom DNA polymerase γ mutations. Cell Mol Life Sci. 2011 Jan;68(2):219-33. doi:10.1007/s00018-010-0530-4.
  8. 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 BroeckhovenC. Recessive POLG mutations presenting with sensory and ataxic neuropathy incompound heterozygote patients with progressive external ophthalmoplegia.Neuromuscul Disord. 2003 Feb;13(2):133-42.
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Subjects: Genetics & Heredity
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Catherine Yang
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Update Date: 24 Dec 2020
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