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Pantothenate kinase-associated neurodegeneration

Reviewed October 2006

What is pantothenate kinase-associated neurodegeneration?

Pantothenate kinase-associated neurodegeneration (formerly called Hallervorden-Spatz syndrome) is a disorder of the nervous system. This condition is characterized by progressive difficulty with movement, typically beginning in childhood. Movement abnormalities include involuntary muscle spasms, rigidity, and trouble with walking that worsens over time. Many people with this condition also develop problems with speech (dysarthria), and some develop vision loss. Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, personality changes, and depression.

Pantothenate kinase-associated neurodegeneration is characterized by an abnormal buildup of iron in certain areas of the brain. A particular change called the eye-of-the-tiger sign, which indicates an accumulation of iron, is typically seen on magnetic resonance imaging (MRI) scans of the brain in people with this disorder.

Researchers have described classic and atypical forms of pantothenate kinase-associated neurodegeneration. The classic form usually appears in early childhood, causing severe problems with movement that worsen rapidly. Features of the atypical form appear later in childhood or adolescence and progress more slowly. Signs and symptoms vary, but the atypical form is more likely than the classic form to involve speech defects and psychiatric problems.

A condition called HARP (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration), which was historically described as a separate syndrome, is now considered part of pantothenate kinase-associated neurodegeneration. Although HARP is much rarer than classic pantothenate kinase-associated neurodegeneration, both conditions involve problems with movement, dementia, and vision abnormalities.

How common is pantothenate kinase-associated neurodegeneration?

The precise incidence of this condition is unknown. It is estimated to affect 1 to 3 per million people worldwide.

What genes are related to pantothenate kinase-associated neurodegeneration?

Mutations in the PANK2 gene cause pantothenate kinase-associated neurodegeneration.

The PANK2 gene provides instructions for making an enzyme called pantothenate kinase 2. This enzyme is active in mitochondria, the energy-producing centers within cells, where it plays a critical role in the formation of a molecule called coenzyme A. Found in all living cells, coenzyme A is essential for the body's production of energy from carbohydrates, fats, and some protein building blocks (amino acids).

Mutations in the PANK2 gene likely result in the production of an abnormal version of pantothenate kinase 2 or prevent cells from making any of this enzyme. A lack of functional pantothenate kinase 2 disrupts the production of coenzyme A and allows potentially harmful compounds to build up in the brain. This buildup leads to swelling and tissue damage, and allows iron to accumulate abnormally in certain parts of the brain. Researchers have not determined how these changes result in the specific features of pantothenate kinase-associated neurodegeneration. Because pantothenate kinase 2 functions in mitochondria, the signs and symptoms of this condition may be related to impaired energy production.

Related Gene(s)

Changes in this gene are associated with pantothenate kinase-associated neurodegeneration.

  • PANK2

How do people inherit pantothenate kinase-associated neurodegeneration?

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 pantothenate kinase-associated neurodegeneration?

These resources address the diagnosis or management of pantothenate kinase-associated neurodegeneration and may include treatment providers.

  • Gene Review: Pantothenate Kinase-Associated Neurodegeneration (http://www.ncbi.nlm.nih.gov/books/NBK1490)
  • Genetic Testing Registry: Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1846582)
  • MedlinePlus Encyclopedia: Hallervorden-Spatz Disease (http://www.nlm.nih.gov/medlineplus/ency/article/001225.htm)
  • MedlinePlus Encyclopedia: MRI (http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm)

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

You may find the following resources about pantothenate kinase-associated neurodegeneration 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 pantothenate kinase-associated neurodegeneration?

  • NBIA1
  • Neuroaxonal dystrophy, juvenile-onset
  • Neurodegeneration with Brain Iron Accumulation Type 1
  • PKAN

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 pantothenate kinase-associated neurodegeneration?

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

What glossary definitions help with understanding pantothenate kinase-associated neurodegeneration?

acids ; atypical ; autosomal ; autosomal recessive ; cell ; CoA ; coenzyme A ; dementia ; depression ; dysarthria ; dystonia ; enzyme ; gene ; imaging ; incidence ; inherited ; involuntary ; iron ; juvenile ; kinase ; magnetic resonance imaging ; mitochondria ; molecule ; nervous system ; protein ; recessive ; sign ; substantia nigra ; syndrome ; tissue

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

References

  • Gene Review: Pantothenate Kinase-Associated Neurodegeneration (http://www.ncbi.nlm.nih.gov/books/NBK1490)
  • Gregory A, Hayflick SJ. Neurodegeneration with brain iron accumulation. Folia Neuropathol. 2005;43(4):286-96. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16416393?dopt=Abstract)
  • Hartig MB, Hörtnagel K, Garavaglia B, Zorzi G, Kmiec T, Klopstock T, Rostasy K, Svetel M, Kostic VS, Schuelke M, Botz E, Weindl A, Novakovic I, Nardocci N, Prokisch H, Meitinger T. Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation. Ann Neurol. 2006 Feb;59(2):248-56. (http://www.ncbi.nlm.nih.gov/pubmed/16437574?dopt=Abstract)
  • Hayflick SJ, Westaway SK, Levinson B, Zhou B, Johnson MA, Ching KH, Gitschier J. Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N Engl J Med. 2003 Jan 2;348(1):33-40. (http://www.ncbi.nlm.nih.gov/pubmed/12510040?dopt=Abstract)
  • Hayflick SJ. Pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome). J Neurol Sci. 2003 Mar 15;207(1-2):106-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12614941?dopt=Abstract)
  • Hayflick SJ. Unraveling the Hallervorden-Spatz syndrome: pantothenate kinase-associated neurodegeneration is the name. Curr Opin Pediatr. 2003 Dec;15(6):572-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14631201?dopt=Abstract)
  • Houlden H, Lincoln S, Farrer M, Cleland PG, Hardy J, Orrell RW. Compound heterozygous PANK2 mutations confirm HARP and Hallervorden-Spatz syndromes are allelic. Neurology. 2003 Nov 25;61(10):1423-6. (http://www.ncbi.nlm.nih.gov/pubmed/14638969?dopt=Abstract)
  • Pellecchia MT, Valente EM, Cif L, Salvi S, Albanese A, Scarano V, Bonuccelli U, Bentivoglio AR, D'Amico A, Marelli C, Di Giorgio A, Coubes P, Barone P, Dallapiccola B. The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration. Neurology. 2005 May 24;64(10):1810-2. (http://www.ncbi.nlm.nih.gov/pubmed/15911822?dopt=Abstract)
  • Shevell M. Hallervorden and history. N Engl J Med. 2003 Jan 2;348(1):3-4. (http://www.ncbi.nlm.nih.gov/pubmed/12510036?dopt=Abstract)
  • Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ. A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. Nat Genet. 2001 Aug;28(4):345-9. (http://www.ncbi.nlm.nih.gov/pubmed/11479594?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: October 2006
Published: December 16, 2014