Neuroferritinopathy

Reviewed July 2008

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 50 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.

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.

MedlinePlus - Health information
Health Topic: Blood Disorders (http://www.nlm.nih.gov/medlineplus/blooddisorders.html)
Additional NIH Resources - National Institutes of Health
National Institute of Neurological Disorders and Stroke: Neurodegeneration with Brain Iron Accumulation Information Page (http://www.ninds.nih.gov/disorders/nbia/nbia.htm)
Educational resources - Information pages
Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=385)
Patient support - For patients and families
- Dystonia Medical Research Foundation (http://www.dystonia-foundation.org/)
- Neurodegeneration with Brain Iron Accumulation Disorders Association (http://www.nbiadisorders.org/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1141/)
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Neuroferritinopathy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1853578)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((neuroferritinopathy%5BTIAB%5D)%20OR%20(hereditary%20ferritinopathy%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%202160%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/606159)

What other names do people use for neuroferritinopathy?

basal ganglia disease, adult-onset
ferritin-related neurodegeneration
hereditary ferritinopathy

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 ; 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)
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)
Crompton DE, Chinnery PF, Fey C, Curtis AR, Morris CM, Kierstan J, Burt A, Young F, Coulthard A, Curtis A, Ince PG, Bates D, Jackson MJ, Burn J. Neuroferritinopathy: a window on the role of iron in neurodegeneration. Blood Cells Mol Dis. 2002 Nov-Dec;29(3):522-31. (http://www.ncbi.nlm.nih.gov/pubmed/12547246?dopt=Abstract)
Curtis AR, Fey C, Morris CM, Bindoff LA, Ince PG, Chinnery PF, Coulthard A, Jackson MJ, Jackson AP, McHale DP, Hay D, Barker WA, Markham AF, Bates D, Curtis A, Burn J. Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat Genet. 2001 Aug;28(4):350-4. (http://www.ncbi.nlm.nih.gov/pubmed/11438811?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)
Madsen E, Gitlin JD. Copper and iron disorders of the brain. Annu Rev Neurosci. 2007;30:317-37. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17367269?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.



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