What is neurodegeneration with brain iron accumulation?
Neurodegeneration with brain iron accumulation (NBIA) is a group of rare movement disorders caused by the buildup of iron in the part of the brain that controls movement. Too much iron damages the brain and nervous system, and damage gets worse over time.
Most types of NBIA develop during early childhood, but other types can appear at different times during life.
Variants (also called mutations) in a small group of specific genes cause NBIA. Most types of NBIA are autosomal, which means the gene variants that cause it are on non-sex chromosomes.
Some types of NBIA are sex-linked, which means the gene variants that cause it are on sex chromosomes (X or Y chromosomes). These types of NBIA are inherited in an X-linked pattern. This means a person inherits the condition from the X chromosome.
Symptoms of NBIA
NBIA usually causes uncontrolled muscle movements and other symptoms. Depending on the type of NBIA, people may have different symptoms, including:
NBIA gets worse over time. Most people experience periods of weeks or months where symptoms quickly get worse, with relatively stable periods in between. How quickly symptoms get worse usually depends on the age a person is when their symptoms start. The condition often gets worse faster in people who first have symptoms early in life. For some people with NBIA, movement problems can eventually limit their ability to walk and perform other daily tasks.
Types of NBIA
NBIA includes 10 different disorders, each caused by variants of specific genes on different chromosomes. Symptoms and age of onset vary across the different NBIA types.
In some cases, a person may not have any of the variants known to cause NBIA but may still have iron buildup in their brains.
Aceruloplasminemia
Aceruloplasminemia is a rare type of NBIA that affects adults. In this condition, variants of the CP gene, located on chromosome 3, make a faulty version of a protein that normally helps move iron around in the body.
Aceruloplasminemia is inherited in an autosomal recessive pattern. This means a person must inherit two copies of the affected gene, one from each parent, to have the disease. The parents of a person with an autosomal recessive condition each carry one copy of the altered gene, but they typically don’t show signs and symptoms of the condition.
Beta-Propeller Protein-Associated Neurodegeneration
Beta-propeller protein-associated neurodegeneration (BPAN) is one of the most common types of NBIA. Seizures can be an early symptom of BPAN and typically start in infancy or early childhood. In this condition, altered versions of the WDR45 gene, located on the X chromosome, make a faulty version of a protein that normally gets rid of extra iron in cells.
BPAN is inherited in an X-linked dominant pattern. This means a person only needs to inherit one copy of the affected gene on the X chromosome from either parent to have the disease.
COASY Protein-Associated Neurodegeneration
COASY protein-associated neurodegeneration (CoPAN) is a rare type of NBIA that starts in childhood. Variants in the COASY gene, located on chromosome 17, cause CoPAN.
CoPAN is inherited in an autosomal recessive pattern. This means a person must inherit two copies of the affected gene, one from each parent, to have the disease. The parents of a person with an autosomal recessive condition each carry one copy of the altered gene, but they typically don’t show signs and symptoms of the condition.
Fatty Acid Hydroxylase-Associated Neurodegeneration
Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a rare type of NBIA that starts in childhood. People with FAHN often have vision problems and trouble with balance. Variants in the FA2H gene, located on chromosome 16, make a faulty version of a protein that normally helps nerve cells form a protective wrapper called a myelin sheath.
Neuroferritinopathy is inherited in an autosomal dominant pattern. In these cases, a person only needs to inherit one copy of the affected gene from either parent to have the disease.
Neuroferritinopathy
Neuroferritinopathy is a rare type of NBIA that affects middle-aged adults. Variants of the FTL gene (located on chromosome 19) or the FTH1 gene (located on chromosome 11) cause neuroferritinopathy.
Neuroferritinopathy is inherited in an autosomal dominant pattern. In these cases, a person only needs to inherit one copy of the affected gene from either parent to have the disease.
Kufor-Rakeb Syndrome
Kufor-Rakeb syndrome, sometimes called Parkinson’s Disease 9 or PARK9, is a rare type of NBIA that affects children. Variants in the ATP13A2 gene, located on chromosome 1, cause Kufor-Rakeb syndrome.
Kufor-Rakeb syndrome is inherited in an autosomal recessive pattern. This means a person must inherit two copies of the affected gene, one from each parent, to have the disease. The parents of a person with an autosomal recessive condition each carry one copy of the altered gene, but they typically don’t show signs and symptoms of the condition.
Mitochondrial Membrane Protein Associated Neurodegeneration
Mitochondrial membrane protein associated neurodegeneration (MPAN) is a common type of NBIA. MPAN symptoms typically start in childhood or early adulthood and often cause movement problems, such as difficulty walking. Variants in the C19orf12 gene, located on chromosome 19, cause MPAN.
MPAN is inherited in an autosomal recessive pattern. This means a person must inherit two copies of the affected gene, one from each parent, to have the disease. The parents of a person with an autosomal recessive condition each carry one copy of the altered gene, but they typically don’t show signs and symptoms of the condition.
Panthothenate Kinase-Associated Neurodegeneration
Panthothenate Kinase-Associated Neurodegeneration (PKAN) is a common type of NBIA. It causes movement disorders that usually start in childhood. Variants in the PANK2 gene (located on chromosome 20) cause PKAN.
PKAN is inherited in an autosomal recessive pattern. This means a person must inherit two copies of the affected gene, one from each parent, to have the disease. The parents of a person with an autosomal recessive condition each carry one copy of the altered gene, but they typically don’t show signs and symptoms of the condition.
PLA2G6-Associated Neurodegeneration
PLA2G6-Associated Neurodegeneration (PLAN) is a common type of NBIA that has several types, including infantile neuroaxonal dystrophy. Variants in the PLA2G6 gene, located on chromosome 22, make a faulty version of a protein that helps cells maintain their protective outer membrane.
PLAN is inherited in an autosomal recessive pattern. This means a person must inherit two copies of the affected gene, one from each parent, to have the disease. The parents of a person with an autosomal recessive condition each carry one copy of the altered gene, but they typically don’t show signs and symptoms of the condition.
Woodhouse-Sakati Syndrome
Woodhouse-Sakati syndrome is a rare type of NBIA that affects hormone levels. People with Woodhouse-Sakati often experience hair loss, delayed puberty, and other hormone-related symptoms, such as infertility. Variants in the DCAF17 gene, located on chromosome 2, cause Woodhouse-Sakati syndrome.
Woodhouse-Sakati syndrome is inherited in an autosomal recessive pattern. This means a person must inherit two copies of the affected gene, one from each parent, to have the disease. The parents of a person with an autosomal recessive condition each carry one copy of the altered gene, but they typically don’t show signs and symptoms of the condition.
Who is more likely to get neurodegeneration with brain iron accumulation?
All 10 types of NBIA are inherited, so people who have a family member with NBIA are at a higher risk of having NBIA themselves. However, NBIA disorders are passed from parents to children in different ways, which affects risk.
If you think someone in your family may have NBIA or that you might be a carrier, let your medical team know, and they may refer you for genetic testing.
How is neurodegeneration with brain iron accumulation diagnosed and treated?
Diagnosing NBIA
Doctors typically diagnose NBIA based on a person’s symptoms, family history, and test results. Since NBIA disorders are inherited, a history of family members with NBIA may help doctors diagnose someone with NBIA symptoms.
Iron buildup in the brain shows up on an MRI (magnetic resonance imaging), so doctors may suggest this imaging test to help diagnose NBIA. Genetic testing can help identify variants known to cause NBIA and also identify the specific NBIA type.
Learn more about neurological diagnostic tests and procedures.
Treating NBIA
NBIA does not currently have a cure, and it doesn’t have a standard course of treatment since NBIA types are quite different from each other. Medicines can help treat seizures, movement problems, and psychiatric symptoms. In some cases, a type of brain surgery called deep brain stimulation (DBS) or botulinum toxin (muscle-relaxing) injections may also help with movement problems.
Physical therapy and assistive devices (tools or equipment that help people do daily tasks more easily) can help people with NBIA walk, eat, and talk. People with certain types of NBIA may also benefit from occupational therapy, exercise, or speech therapy.
What are the latest updates on neurodegeneration with brain iron accumulation?
The National Institutes of Health (NIH), which includes NINDS, is the leading federal funder of research on the brain and nervous system, including disorders such as NBIA. NIH supports new and innovative research to better understand, diagnose, and treat NBIA.
Current NIH-funded research is exploring the ways that NBIA disorders cause disease. For example, multiple NIH-funded research groups are looking at how altered versions of the ATP13A2 gene cause inherited Parkinson’s diseases like Kufor-Rakeb syndrome. One NIH-funded research group is identifying additional genes and proteins linked to this type of NBIA that may lead to development of medicines to treat ATP13A2-related conditions. Another NIH-funded group is doing research with a model system (worms) to understand how altered versions of the ATP13A2 gene affect the ability of brain cells to communicate.
Additional NIH-funded research is looking at potential treatments for one of the most common NBIA disorders, PKAN, which affects the activity of coenzyme A. This is a common body molecule that makes energy and plays many other roles in body metabolism. Researchers are testing potential medicines that could help treat PKAN by increasing levels of coenzyme A in various ways.
Some NIH-funded studies are looking more generally at how damage to the brain causes NBIA. For example, researchers are looking at ways viruses can cause dementia, which may inform how scientists understand related conditions like NBIA. Other research is exploring how and whether molecules called polyamines, which help cells grow, divide, and stay healthy, harm nerve and brain cells.
For more information on research about NBIA, check NIH RePORTER, a searchable database of current and past research projects funded by NIH and other federal agencies. RePORTER also has links to publications and resources from these projects.
For research articles and summaries on NBIA, search PubMed, which contains citations from medical journals and other sites.
How can I or my loved one help improve care for people with neurodegeneration with brain iron accumulation?
Consider participating in a clinical trial so clinicians and scientists can learn more about NBIA and related disorders. Clinical research with human study participants helps researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.
All types of participants are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities. This helps make sure that study results apply to as many people as possible and that treatments will be safe and effective for everyone who will use them.
For information about participating in clinical research, visit the NINDS Clinical Trials site and NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with NBIA at ClinicalTrials.gov, a searchable database of current and past clinical studies and research results.
Where can I find more information about neurodegeneration with brain iron accumulation?
Information may be available from the following sources: