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Genetics Home Reference: your guide to understanding genetic conditions
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Infantile neuroaxonal dystrophy

Reviewed September 2012

What is infantile neuroaxonal dystrophy?

Infantile neuroaxonal dystrophy is a disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills (developmental regression). In some cases, signs and symptoms of infantile neuroaxonal dystrophy first appear later in childhood or during the teenage years and progress more slowly.

Children with infantile neuroaxonal dystrophy experience progressive difficulties with movement. They generally have muscles that are at first weak and "floppy" (hypotonic), and then gradually become very stiff (spastic). Eventually, affected children lose the ability to move independently. Lack of muscle strength causes difficulty with feeding. Muscle weakness can also result in breathing problems that can lead to frequent infections, such as pneumonia. Seizures occur in some affected children.

Rapid, involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and vision loss due to deterioration (atrophy) of the nerve that carries information from the eye to the brain (the optic nerve) often occur in infantile neuroaxonal dystrophy. Hearing loss may also develop. Children with this disorder experience progressive deterioration of cognitive functions (dementia), and they eventually lose awareness of their surroundings.

Infantile neuroaxonal dystrophy is characterized by the development of swellings called spheroid bodies in the axons, the fibers that extend from nerve cells (neurons) and transmit impulses to muscles and other neurons. In some individuals with infantile neuroaxonal dystrophy, abnormal amounts of iron accumulate in a specific region of the brain called the basal ganglia. The relationship of these features to the symptoms of infantile neuroaxonal dystrophy is unknown.

How common is infantile neuroaxonal dystrophy?

Infantile neuroaxonal dystrophy is a very rare disorder. Its specific incidence is unknown.

What genes are related to infantile neuroaxonal dystrophy?

Mutations in the PLA2G6 gene have been identified in most individuals with infantile neuroaxonal dystrophy. The PLA2G6 gene provides instructions for making a type of enzyme called an A2 phospholipase. This type of enzyme is involved in breaking down (metabolizing) fats called phospholipids. Phospholipid metabolism is important for many body processes, including helping to keep the cell membrane intact and functioning properly. Specifically, the A2 phospholipase produced from the PLA2G6 gene, sometimes called PLA2 group VI, helps to regulate the levels of a compound called phosphatidylcholine, which is abundant in the cell membrane.

Mutations in the PLA2G6 gene impair the function of the PLA2 group VI enzyme, which may disrupt cell membrane maintenance and contribute to the development of spheroid bodies in the nerve axons. Although it is unknown how changes in this enzyme's function lead to the signs and symptoms of infantile neuroaxonal dystrophy, phospholipid metabolism problems have been seen in both this disorder and a similar disorder called pantothenate kinase-associated neurodegeneration. These disorders, as well as the more common Alzheimer disease and Parkinson disease, also are associated with changes in brain iron metabolism. Researchers are studying the links between phospholipid defects, brain iron, and damage to nerve cells, but have not determined how the iron accumulation that occurs in some individuals with infantile neuroaxonal dystrophy may contribute to the features of this disorder.

A few individuals with infantile neuroaxonal dystrophy have not been found to have mutations in the PLA2G6 gene. The genetic cause of the condition in these cases is unknown; there is evidence that at least one other unidentified gene may be involved.

Related Gene(s)

Changes in this gene are associated with infantile neuroaxonal dystrophy.

  • PLA2G6

How do people inherit infantile neuroaxonal dystrophy?

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 infantile neuroaxonal dystrophy?

These resources address the diagnosis or management of infantile neuroaxonal dystrophy and may include treatment providers.

  • Gene Review: PLA2G6-Associated Neurodegeneration (http://www.ncbi.nlm.nih.gov/books/NBK1675)
  • Genetic Testing Registry: Infantile neuroaxonal dystrophy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0270724)

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

You may find the following resources about infantile neuroaxonal dystrophy 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 infantile neuroaxonal dystrophy?

  • INAD
  • NBIA, PLA2G6-related
  • neurodegeneration with brain iron accumulation, PLA2G6-related
  • Seitelberger disease
  • Seitelberger's disease

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 infantile neuroaxonal dystrophy?

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

What glossary definitions help with understanding infantile neuroaxonal dystrophy?

atrophy ; autosomal ; autosomal recessive ; axons ; cell ; cell membrane ; compound ; dementia ; enzyme ; gene ; incidence ; inherited ; involuntary ; iron ; kinase ; metabolism ; motor ; nervous system ; nystagmus ; optic nerve ; phospholipid ; phospholipids ; pneumonia ; recessive ; regression ; strabismus ; teenage

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

References

  • Engel LA, Jing Z, O'Brien DE, Sun M, Kotzbauer PT. Catalytic function of PLA2G6 is impaired by mutations associated with infantile neuroaxonal dystrophy but not dystonia-parkinsonism. PLoS One. 2010 Sep 23;5(9):e12897. doi: 10.1371/journal.pone.0012897. (http://www.ncbi.nlm.nih.gov/pubmed/20886109?dopt=Abstract)
  • Hayflick SJ. Neurodegeneration with brain iron accumulation: from genes to pathogenesis. Semin Pediatr Neurol. 2006 Sep;13(3):182-5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17101457?dopt=Abstract)
  • Khateeb S, Flusser H, Ofir R, Shelef I, Narkis G, Vardi G, Shorer Z, Levy R, Galil A, Elbedour K, Birk OS. PLA2G6 mutation underlies infantile neuroaxonal dystrophy. Am J Hum Genet. 2006 Nov;79(5):942-8. Epub 2006 Sep 19. (http://www.ncbi.nlm.nih.gov/pubmed/17033970?dopt=Abstract)
  • Kurian MA, Morgan NV, MacPherson L, Foster K, Peake D, Gupta R, Philip SG, Hendriksz C, Morton JE, Kingston HM, Rosser EM, Wassmer E, Gissen P, Maher ER. Phenotypic spectrum of neurodegeneration associated with mutations in the PLA2G6 gene (PLAN). Neurology. 2008 Apr 29;70(18):1623-9. doi: 10.1212/01.wnl.0000310986.48286.8e. (http://www.ncbi.nlm.nih.gov/pubmed/18443314?dopt=Abstract)
  • McNeill A, Chinnery PF. Neurodegeneration with brain iron accumulation. Handb Clin Neurol. 2011;100:161-72. doi: 10.1016/B978-0-444-52014-2.00009-4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21496576?dopt=Abstract)
  • Morgan NV, Westaway SK, Morton JE, Gregory A, Gissen P, Sonek S, Cangul H, Coryell J, Canham N, Nardocci N, Zorzi G, Pasha S, Rodriguez D, Desguerre I, Mubaidin A, Bertini E, Trembath RC, Simonati A, Schanen C, Johnson CA, Levinson B, Woods CG, Wilmot B, Kramer P, Gitschier J, Maher ER, Hayflick SJ. PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron. Nat Genet. 2006 Jul;38(7):752-4. Epub 2006 Jun 18. Erratum in: Nat Genet. 2006 Aug;38(8):957. (http://www.ncbi.nlm.nih.gov/pubmed/16783378?dopt=Abstract)
  • OMIM: NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A (http://omim.org/entry/256600)
  • Polster B, Crosier M, Lindsay S, Hayflick S. Expression of PLA2G6 in human fetal development: Implications for infantile neuroaxonal dystrophy. Brain Res Bull. 2010 Nov 20;83(6):374-9. doi: 10.1016/j.brainresbull.2010.08.011. Epub 2010 Sep 9. (http://www.ncbi.nlm.nih.gov/pubmed/20813170?dopt=Abstract)
  • Schneider SA, Hardy J, Bhatia KP. Syndromes of neurodegeneration with brain iron accumulation (NBIA): an update on clinical presentations, histological and genetic underpinnings, and treatment considerations. Mov Disord. 2012 Jan;27(1):42-53. doi: 10.1002/mds.23971. Epub 2011 Oct 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22031173?dopt=Abstract)
  • Wu Y, Jiang Y, Gao Z, Wang J, Yuan Y, Xiong H, Chang X, Bao X, Zhang Y, Xiao J, Wu X. Clinical study and PLA2G6 mutation screening analysis in Chinese patients with infantile neuroaxonal dystrophy. Eur J Neurol. 2009 Feb;16(2):240-5. doi: 10.1111/j.1468-1331.2008.02397.x. Epub 2008 Dec 9. (http://www.ncbi.nlm.nih.gov/pubmed/19138334?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: September 2012
Published: September 29, 2014