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Genetics Home Reference: your guide to understanding genetic conditions
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Neuroferritinopathy

Reviewed August 2014

What is neuroferritinopathy?

Neuroferritinopathy is a disorder in which iron gradually accumulates in the brain. Certain brain regions that help control movement (basal ganglia) are particularly affected. People with neuroferritinopathy have progressive problems with movement that begin at about age 40. These movement problems can include involuntary jerking motions (chorea), rhythmic shaking (tremor), difficulty coordinating movements (ataxia), or uncontrolled tensing of muscles (dystonia). Symptoms of the disorder may be more apparent on one side of the body than on the other. Affected individuals may also have difficulty swallowing (dysphagia) and speaking (dysarthria).

Intelligence is unaffected in most people with neuroferritinopathy, but some individuals develop a gradual decline in thinking and reasoning abilities (dementia). Personality changes such as reduced inhibitions and difficulty controlling emotions may also occur as the disorder progresses.

How common is neuroferritinopathy?

The prevalence of neuroferritinopathy is unknown. Fewer than 100 individuals with this disorder have been reported.

What genes are related to neuroferritinopathy?

Mutations in the FTL gene cause neuroferritinopathy. The FTL gene provides instructions for making the ferritin light chain, which is one part (subunit) of a protein called ferritin. Ferritin stores and releases iron in cells. Each ferritin molecule can hold as many as 4,500 iron atoms. This storage capacity allows ferritin to regulate the amount of iron in the cells and tissues.

Mutations in the FTL gene that cause neuroferritinopathy are believed to reduce ferritin's ability to store iron, resulting in the release of excess iron in nerve cells (neurons) of the brain. The cells may respond by producing more ferritin in an attempt to handle the free iron. Excess iron and ferritin accumulate in the brain, particularly in the basal ganglia, resulting in the movement problems and other neurological changes seen in neuroferritinopathy.

Related Gene(s)

Changes in this gene are associated with neuroferritinopathy.

  • FTL

How do people inherit neuroferritinopathy?

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

In most cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of neuroferritinopathy?

These resources address the diagnosis or management of neuroferritinopathy and may include treatment providers.

  • Gene Review: Neuroferritinopathy (http://www.ncbi.nlm.nih.gov/books/NBK1141)
  • Genetic Testing Registry: Neuroferritinopathy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1853578)

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

You may find the following resources about neuroferritinopathy 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 neuroferritinopathy?

  • basal ganglia disease, adult-onset
  • ferritin-related neurodegeneration
  • hereditary ferritinopathy
  • NBIA3
  • neurodegeneration with brain iron accumulation 3

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 neuroferritinopathy?

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

What glossary definitions help with understanding neuroferritinopathy?

ataxia ; autosomal ; autosomal dominant ; cell ; chorea ; dementia ; difficulty swallowing ; dysarthria ; dysphagia ; dystonia ; gene ; hereditary ; inherited ; involuntary ; iron ; molecule ; mutation ; neurological ; prevalence ; protein ; subunit ; tremor

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

References

  • Burn J, Chinnery PF. Neuroferritinopathy. Semin Pediatr Neurol. 2006 Sep;13(3):176-81. (http://www.ncbi.nlm.nih.gov/pubmed/17101456?dopt=Abstract)
  • Burn J. Neuroferritinopathy: iron in the brain. Mol Cytogenet. 2014 Jan 21;7(Suppl 1 Proceedings of the International Conference on Human):I36. doi: 10.1186/1755-8166-7-S1-I36. eCollection 2014. (http://www.ncbi.nlm.nih.gov/pubmed/24949097?dopt=Abstract)
  • Crompton DE, Chinnery PF, Bates D, Walls TJ, Jackson MJ, Curtis AJ, Burn J. Spectrum of movement disorders in neuroferritinopathy. Mov Disord. 2005 Jan;20(1):95-9. (http://www.ncbi.nlm.nih.gov/pubmed/15390132?dopt=Abstract)
  • Keogh MJ, Jonas P, Coulthard A, Chinnery PF, Burn J. Neuroferritinopathy: a new inborn error of iron metabolism. Neurogenetics. 2012 Feb;13(1):93-6. doi: 10.1007/s10048-011-0310-9. Epub 2012 Jan 26. (http://www.ncbi.nlm.nih.gov/pubmed/22278127?dopt=Abstract)
  • Keogh MJ, Morris CM, Chinnery PF. Neuroferritinopathy. Int Rev Neurobiol. 2013;110:91-123. doi: 10.1016/B978-0-12-410502-7.00006-5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/24209436?dopt=Abstract)
  • Lehn A, Boyle R, Brown H, Airey C, Mellick G. Neuroferritinopathy. Parkinsonism Relat Disord. 2012 Sep;18(8):909-15. doi: 10.1016/j.parkreldis.2012.06.021. Epub 2012 Jul 17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22818529?dopt=Abstract)
  • Levi S, Cozzi A, Arosio P. Neuroferritinopathy: a neurodegenerative disorder associated with L-ferritin mutation. Best Pract Res Clin Haematol. 2005 Jun;18(2):265-76. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15737889?dopt=Abstract)
  • McNeill A, Chinnery PF. Neuroferritinopathy: update on clinical features and pathogenesis. Curr Drug Targets. 2012 Aug;13(9):1200-3. (http://www.ncbi.nlm.nih.gov/pubmed/22515742?dopt=Abstract)
  • OMIM: NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 3 (http://omim.org/entry/606159)
  • Vidal R, Ghetti B, Takao M, Brefel-Courbon C, Uro-Coste E, Glazier BS, Siani V, Benson MD, Calvas P, Miravalle L, Rascol O, Delisle MB. Intracellular ferritin accumulation in neural and extraneural tissue characterizes a neurodegenerative disease associated with a mutation in the ferritin light polypeptide gene. J Neuropathol Exp Neurol. 2004 Apr;63(4):363-80. (http://www.ncbi.nlm.nih.gov/pubmed/15099026?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: August 2014
Published: November 17, 2014