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Disease Profile
Pantothenate kinase-associated neurodegeneration
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000
Age of onset
All ages
ICD-10
G23.0
Inheritance
Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.
Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.
X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.
Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.
Not applicable
Other names (AKA)
PKAN; Neurodegeneration with brain iron accumulation; NBIA;
Categories
Nervous System Diseases
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
Symptoms
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
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.
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 | |
Abnormal foot morphology |
Abnormal feet structure
Abnormality of the feet
Abnormality of the foot
Foot deformities
Foot deformity
[ more ] |
0001760 |
Choreoathetosis | 0001266 | |
Constipation | 0002019 | |
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 | 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, progressive
Progressive dementia
[ more ] |
0000726 | |
Depressivity |
Depression
|
0000716 |
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 |
Obsessive-compulsive traits
|
0008770 |
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 | |
0001251 | ||
0000007 | ||
Blepharospasm |
Eyelid spasm
Eyelid twitching
Involuntary closure of eyelid
Spontaneous closure of eyelid
[ more ] |
0000643 |
Cerebral degeneration | 0007313 | |
Decreased muscle mass | 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 |
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 |
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
- 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
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.
|
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: [email protected]
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: [email protected]
Website: https://nbiacure.org/
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
- MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
- Genetics Home Reference (GHR) contains information on Pantothenate kinase-associated neurodegeneration. This website is maintained by the National Library of Medicine.
- 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.
References
- Pantothenate kinase-associated neurodegeneration. Genetics Home Reference. 2015; https://www.ghr.nlm.nih.gov/condition/pantothenate-kinase-associated-neurodegeneration.
- Gregory A & Hayflick SJ. Pantothenate Kinase-Associated Neurodegeneration. GeneReviews. 2013; https://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/.
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