Pantothenate kinase-associated neurodegeneration

Información en español 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

Subtypes:

Beta-Propeller Protein-Associated Neurodegeneration ; Mitochondrial Membrane Protein-Associated Neurodegeneration

This disease is grouped under:

Neuroacanthocytosis; Neurodegeneration with brain iron accumulation

Summary Summary

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disease characterized by a progressive degeneration of the nervous system (neurodegenerative disorder) and buildup of iron in the brain. PKAN is usually classified into two forms: classic and atypical. Classic PKAN causes 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 a buildup 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 mutations in the PANK2 gene.^[1]^[2] Treatment depends on the symptoms, and may include medication (such as botulinum toxin), surgery, deep brain stimulation and physical therapy.^[2]^[3] Research for a more effective treatment is ongoing.^[2]^[3]^[4]

Last updated: 7/10/2017

Symptoms Symptoms

There are two forms of PKAN, classical and atypical.

Classic PKAN: Symptoms of classic PKAN develop during early childhood, usually before age 10, and usually include:^[5]^[6]

Dystonia (sustained muscle contractions causing repetitive movements) and poor balance: The first symptom is often difficulty 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 and affect the arms. As affected individuals age, they may eventually lose control of voluntary movements. Muscle spasms combined with decreased bone mass can result in bone fractures. The disease may be stable 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.
Speech, chewing and swallowing problems: Many people may have speech problems and may also have enough trouble with chewing and swallowing that a feeding tube becomes necessary, due to dystonia affecting the muscles in the mouth and throat.
Vision problems: Two-thirds of children with classical PKAN develop peripheral (side) vision loss and night blindness due to a degeneration of parts of the retina.
Intellectual disability: Cognitive functioning varies from person to person and can range from high average to below average.

Atypical form: Features of the atypical form usually progress more slowly and appear within the first three decades of life. Signs and symptoms may include:^[2]^[6]

Speech difficulty: Are usually the first symptoms, characterized 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, violent outburst, and depression are more commonly observed.
Movement problems: While movement problems are a common feature, it usually develops later than the classic form. Loss of independent walking often occurs 15-40 years after the initial development of symptoms.
Vision problems: Retinal degeneration is rare in the atypical form.

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]

Last updated: 7/10/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 53 |

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Gait disturbance	Abnormal gait Abnormal walk Impaired gait [ more ]	0001288
Iris hypopigmentation	Light eye color	0007730
30%-79% of people have these symptoms
Abnormal cranial nerve morphology		0001291
Abnormality of the foot	Abnormal feet morphology Abnormality of the feet Foot deformities Foot deformity [ more ]	0001760
Choreoathetosis		0001266
Constipation		0002019
Dysphagia	Poor swallowing Swallowing difficulties Swallowing difficulty [ more ]	0002015
Gastroesophageal reflux	Acid reflux Acid reflux disease Heartburn [ more ]	0002020
Hyperreflexia	Increased reflexes	0001347
Recurrent respiratory infections	Frequent respiratory infections Multiple respiratory infections respiratory infections, recurrent Susceptibility to respiratory infections [ more ]	0002205
Rigidity	Muscle rigidity	0002063
Spasticity	Involuntary muscle stiffness, contraction, or spasm	0001257
Tremor	Tremors	0001337
5%-29% of people have these symptoms
Abnormality of skin pigmentation	Abnormal pigmentation Abnormal skin color Abnormal skin pigmentation Abnormality of pigmentation Pigmentary changes Pigmentary skin changes Pigmentation anomaly [ more ]	0001000
Akinesia		0002304
Bradykinesia	Slow movements Slowness of movements [ more ]	0002067
Cachexia	Wasting syndrome	0004326
Dementia	Dementia, progressive Progressive dementia [ more ]	0000726
Depressivity	Depression	0000716
Developmental regression	Loss of developmental milestones Mental deterioration in childhood [ more ]	0002376
Dysarthria	Difficulty articulating speech	0001260
Dysphonia	Inability to produce voice sounds	0001618
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Joint dislocation	Joint dislocations Recurrent joint dislocations [ more ]	0001373
Obsessive-compulsive trait	Obsessive-compulsive traits	0008770
Seizures	Seizure	0001250
Visual impairment	Impaired vision Loss of eyesight Poor vision [ more ]	0000505
Percent of people who have these symptoms is not available through HPO
Abnormal pyramidal sign		0007256
Acanthocytosis		0001927
Ataxia		0001251
Autosomal recessive inheritance		0000007
Blepharospasm	Eyelid spasm Eyelid twitching Involuntary closure of eyelid Spontaneous closure of eyelid [ more ]	0000643
Cerebral degeneration		0007313
Decreased muscle mass	Underdeveloped muscles	0003199
Eye of the tiger anomaly of globus pallidus		0002454
Eyelid apraxia	Difficulty opening the eyelids	0000658
Facial grimacing		0000273
Feeding difficulties in infancy		0008872
Global brain atrophy	Generalized brain degeneration	0002283
Global developmental delay		0001263
Hyperactivity	More active than typical	0000752
Hyperpigmentation of the skin	Patchy darkened skin	0000953
Motor tics		0100034
Myopathy	Muscle tissue disease	0003198
Neurodegeneration	Ongoing loss of nerve cells	0002180
Optic atrophy		0000648
Orofacial dyskinesia		0002310
Palilalia		0031814
Parkinsonism		0001300
Pigmentary retinopathy		0000580
Rapidly progressive	Worsening quickly	0003678
Retinal degeneration	Retina degeneration	0000546
Urinary incontinence	Loss of bladder control	0000020

Showing of 53 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 6/1/2019

Do you have updated information on this disease? We want to hear from you.

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

The treatment of patients with PKAN is mostly symptomatic, and may include:^[2]^[5]^[3]^[4]^[6]

Medication: The tremors best respond to dopaminergic agents. Benzodiazepines are used to improve muscular contraction and twisting and writhing movements. Dystonia is treated with oral trihexyphenidyl, oral baclofen or a baclofen pump, and oral clonazepam. Intramuscular botulinum toxin is used for muscle spasms, especially in treating a limited body region (injections in the facial muscles can greatly improve speech and eating abilities). Methscopolamine bromide can be used for excessive drooling.
Surgical procedures: Procedures to destroy specific parts of the brain, the pallidus (ablative pallidotomy) or the thalamus (thalmotomy) may provide temporary relief for dystonia.
Deep brain stimulation: A procedure where a medical device called a brain pacemaker is implanted to send electric impulses to specific parts of the brain for the treatment of movement and mood disorders.
Services for the blind and educational programs.
Physical therapy and occupational therapy to maintain normal joint mobility
Adaptive aids (walker, wheelchair) for gait abnormalities.
Speech therapy and/or communication devices.

Drugs that reduce the levels of iron in the body (iron chelation) may be effective in some cases but more studies are needed. Supplements of vitamin B5 (pantothenate) may be helpful in people with the atypical PKAN but there are not enough studies confirming that it is effective.^[6]

A recent study with one patient using a medication known as fosmetpantotenate, which restores the CoA levels (a helper molecule, needed for the activation of several enzymes) decreased in this disease, showed good results.^[4]

Last updated: 7/10/2017

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare 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 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.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include Wilson disease (see this term), which is excluded by normal plasma ceruloplasmin concentration or copper metabolism, and other types of NBIA, which can be differentiated using MRI findings and genetic testing. Visit the Orphanet disease page for more information.

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 related to 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.
The NBIA Disorders Association posts information on the latest clinical trials and research studies where you can learn about opportunities to take part in research.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s 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: +1-619-588-2315
Fax: +1-619-588-4093
E-mail: info@NBIAdisorders.org
Website: https://www.nbiadisorders.org/
NBIAcure
Molecular & Medical Genetics
Oregon Health & Science University
3181 S.W. Sam Jackson Park Rd. L103
Portland, OR 97239
E-mail: info@NBIAcure.org
Website: http://nbiacure.org/

Do you know of an organization? We want to hear from you.

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

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.
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

Other Conferences

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

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. 2015; http://www.ghr.nlm.nih.gov/condition/pantothenate-kinase-associated-neurodegeneration.
Gregory A & Hayflick SJ. Pantothenate Kinase-Associated Neurodegeneration. GeneReviews. 2013; http://www.ncbi.nlm.nih.gov/books/NBK1490/.
Bokhari M, Bokhari SR. Hallervorden Spatz Disease (Pantothenate Kinase-Associated Neurodegeneration, PKAN). StatPearls. June, 2017; https://www.ncbi.nlm.nih.gov/books/NBK430689/.
Christou Y-P, Tanteles GA, Kkolou E, et al. Open-Label Fosmetpantotenate, a Phosphopantothenate Replacement Therapy in a Single Patient with Atypical PKAN doi:10.1155/2017/3247034.. Case Reports in Neurological Medicine. 2017; 2017:3247034. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439260/.
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;
Pantothenate Kinase-Associated Neurodegeneration. NORD. 2016; https://rarediseases.org/rare-diseases/pantothenate-kinase-associated-neurodegeneration/.