Pantothenate kinase-associated neurodegeneration

Title

Other Names:

PKAN; Neurodegeneration with brain iron accumulation; NBIA; PKAN; Neurodegeneration with brain iron accumulation; NBIA; Neuroaxonal dystrophy, late infantile; Hallervorden-Spatz disease See More

Categories:

Nervous System Diseases

Summary Summary

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, movement disorder characterized by a progressive degeneration of the nervous system (neurodegenerative disorder). PKAN is generally separated into classic and atypical forms. Children with classic PKAN develop symptoms in the first ten years of life. The atypical form of PKAN usually occurs after the age of ten and progresses more slowly. All individuals with PKAN have 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. PKAN is inherited in an autosomal recessive manner and is caused by changes (mutations) in the PANK2 gene.^[1]^[2]

Last updated: 9/23/2011

Symptoms Symptoms

There are two forms of PKAN, classical and atypical. Symptoms of classic PKAN develop during early childhood, usually before age 10. The first symptom is often difficutly with movement and walking. Children are often first considered clumsy as their legs can be rigid, dystonic (an abnormality of muscle tone) and have involuntary muscle spasms (spasticity); these symptoms worsen over time. People can plateau for long periods of time and then undergo intervals of rapid deterioration, often lasting one to two months. Children usually lose the ability to walk by 10-15 years after the beginning of symptoms.^[3]

Many individuals also experience limited speech and may have enough trouble with chewing and swallowing that a feeding tube becomes necessary. Two-thirds of children with classical PKAN develop peripheral (side) vision loss and night blindness due to retinal degeneration. Cognitive functioning varies from person to person and can range from high average to below average.^[3] Premature death does occur; however, live span is variable. With improvements in medical care, a greater number of affected individuals are living into adulthood.^[2]

All individuals with PKAN have 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.^[1]

Features of the atypical form usually progress more slowly and appear within the first three decades of life. Signs and symptoms vary, but the progression in the atypical form is usually slower. Symptoms are usually marked by speech difficulty such repetition of words or phrases (palilalia), rapid speech (tachylalia), and poor articulation/slurring (dysarthria). Psychiatric symptoms such as behavioral problems, personality changes, and depression are more commonly observed. While movement problems are a common feature, it usually develops later. Loss of independent walking often occurs 15-40 years after the initial development of symptoms. Retinal degeneration is rare in the atypical form.^[2]

Last updated: 9/23/2011

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Gait disturbance	Very frequent (present in 80%-99% of cases)
Iris hypopigmentation	Very frequent (present in 80%-99% of cases)
Abnormality of the cranial nerves	Frequent (present in 30%-79% of cases)
Abnormality of the foot	Frequent (present in 30%-79% of cases)
Choreoathetosis	Frequent (present in 30%-79% of cases)
Constipation	Frequent (present in 30%-79% of cases)
Dysphagia	Frequent (present in 30%-79% of cases)
Gastroesophageal reflux	Frequent (present in 30%-79% of cases)
Hyperreflexia	Frequent (present in 30%-79% of cases)
Recurrent respiratory infections	Frequent (present in 30%-79% of cases)
Rigidity	Frequent (present in 30%-79% of cases)
Spasticity	Frequent (present in 30%-79% of cases)
Tremor	Frequent (present in 30%-79% of cases)
Abnormality of skin pigmentation	Occasional (present in 5%-29% of cases)
Akinesia	Occasional (present in 5%-29% of cases)
Bradykinesia	Occasional (present in 5%-29% of cases)
Cachexia	Occasional (present in 5%-29% of cases)
Dementia	Occasional (present in 5%-29% of cases)
Depression	Occasional (present in 5%-29% of cases)
Developmental regression	Occasional (present in 5%-29% of cases)
Dysarthria	Occasional (present in 5%-29% of cases)
Dysphonia	Occasional (present in 5%-29% of cases)
Failure to thrive	Occasional (present in 5%-29% of cases)
Joint dislocation	Occasional (present in 5%-29% of cases)
Obsessive-compulsive trait	Occasional (present in 5%-29% of cases)
Seizures	Occasional (present in 5%-29% of cases)
Visual impairment	Occasional (present in 5%-29% of cases)
Abnormal pyramidal signs	-
Acanthocytosis	-
Ataxia	-
Autosomal recessive inheritance	-
Behavioral abnormality	-
Blepharospasm	-
Cerebral degeneration	-
Decreased muscle mass	-
Eye of the tiger anomaly of globus pallidus	-
Eyelid apraxia	-
Facial grimacing	-
Feeding difficulties in infancy	-
Global brain atrophy	-
Hyperactivity	-
Hyperpigmentation of the skin	-
Motor tics	-
Myopathy	-
Neurodegeneration	-
Optic atrophy	-
Orofacial dyskinesia	-
Parkinsonism	-
Pigmentary retinopathy	-
Rapidly progressive	-
Retinal degeneration	-
Urinary incontinence	-

Last updated: 5/8/2017

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment Treatment

Currently there is no cure for this condition. Treatment consists of medications and surgery to relieve symptoms. For many of the treatments that do improve symptoms, the period of benefit is limited. Baclofen and trihexyphenidyl remain the most effective drugs for the dystonia and spasticity associated with this condition. Botulinum toxin may be helpful for many affected individuals, especially in treating a limited body region. For example, injections in the facial muscles can greatly improve speech and eating abilities. Those with PKAN typically do not benefit from L-dopa. Deep brain stimulation (DBS) is also an option for relieving some symptoms; an international study of the effectiveness of DBS is currently underway. Recently, interest in chelating agents (agents that remove iron from the body) has also been revived, although the benefits have not yet been documented and systemic anemia remains a risk. A trial using deferriprone (a chelator) in PKAN is currently underway in Italy. Click on the link to learn more about this study.^[3]

Last updated: 9/23/2011

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Pantothenate kinase-associated neurodegeneration. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

NBIA Disorders Association
2082 Monaco Ct.
El Cajon, CA 92019-4235
Telephone: 619-588-2315
Fax: 619-588-4093
E-mail: info@NBIAdisorders.org
Website: http://www.nbiadisorders.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Pantothenate kinase-associated neurodegeneration. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Pantothenate kinase-associated neurodegeneration. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

A Gregory1, B J Polster1, and S J Hayflick. Clinical and genetic delineation of neurodegeneration with brain
iron accumulation. J Med Genet. 2009 February; 46(2): 73–80.

News & Events News & Events

News

NBIA Disorders Association Announces Research Grants for Neurodegeneration with Brain Iron Accumulation (NBIA)
February 19, 2015

NCATS Co-Sponsored Conferences

Brain, Blood and Iron: Joint International Symposium on Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation Friday, October 1, 2010 - Saturday, October 2, 2010
Location: Doubletree Hotel,, Bethesda, Maryland
Description: The overall objectives of this workshop were to (1) define neuroacanthocytosis (NA) and neurodegeneration with brain iron accumulation (NBIA) research priorities; (2) determine resources that are needed in order to foster research; (3) stimulate interest in research into NA and NBIA among scientists in related fields; (4) generate collaborations between those working in related disciplines, with particular relevance to NA and NBIA; and (5) attract early career investigators to these fields.

Contact: Dr. Danilo A. Tagle(301) 496-5745tagled@mninds.nih.gov

Co-funding Institute(s): National Institute of Neurological Disorders and Stroke, Office of Rare Diseases Research
- Agenda ( - 56KB)
- Other Materials ( - 30KB)
- Summary ( - 43KB)
Third Genome Dynamics in the Neurosciences Conference Sunday, July 18, 2010 - Thursday, July 22, 2010
Location: The Hilton Metropole, Brighton, England
Description: The goal of this meeting was to integrate basic processes of DNA damage signaling and repair and clinical aspects of neurological and neurodegenerative disease. The program was designed to bring together leading scientists with primary interests in DNA damage signaling with those working in specific related neurodegenerative disease areas as a means for integrating these fields. It was anticipated that this would generate insights into how normal processes of genome maintenance in the brain contribute to the prevention of a wide range of diseases.

Contact: Dr. Danilo A. Tagle, NINDS(301) 496-5745tagled@mninds.nih.gov

Co-funding Institute(s): National Institute of Neurological Disorders and Stroke, Office of Rare Diseases Research
- Agenda ( - 42KB)
- Speakers ( - 47KB)
- Summary ( - 13KB)

Other Conferences

Fifth International NBIA Disorders Association Family Conference
May 29 - 31, 2009
Indianapolis, Indiana
http://www.nbiadisorders.org/

Related Diseases Related Diseases

The following diseases are related to Pantothenate kinase-associated neurodegeneration. If you have a question about any of these diseases, you can contact GARD.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I am looking for treatment information for PKAN. My brother was diagnosed with it a little over a year ago. It started about age 3 with all the classic signs. He now is in very bad shape. I am looking for any help. He may start a clinical trial of deferiprone treatment if approved by the FDA. See answer

Have a question? Contact a GARD Information Specialist.

References References

Pantothenate kinase-associated neurodegeneration. Genetics Home Reference. October 2006; http://www.ghr.nlm.nih.gov/condition/pantothenate-kinase-associated-neurodegeneration. Accessed 9/23/2011.
Gregory A & Hayflick SJ. Pantothenate Kinase-Associated Neurodegeneration. GeneReviews. March 2010; http://www.ncbi.nlm.nih.gov/books/NBK1490/. Accessed 9/23/2011.
Gregory, A. Polster, B J, and Hayflick, S J. Clinical and genetic delineation of neurodegeneration with brain iron accumulation. Journal of Medical Genetics. February 2009;

Do you know of a review article? Send us your suggestions.