Pantothenate Kinase-associated Neurodegeneration
Disease Details
Family Health Simplified
- Description
- Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, inherited disorder characterized by progressive degeneration of the nervous system due to abnormal accumulation of iron in the brain.
- Type
- Pantothenate kinase-associated neurodegeneration (PKAN) is a type of neurodegenerative disorder. It is transmitted in an autosomal recessive manner.
- Signs And Symptoms
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Symptoms typically begin in childhood and are progressive, often resulting in death by early adulthood. Symptoms of PKAN begin before middle childhood, and most often are noticed before ten years of age. Symptoms include:
dystonia (repetitive uncontrollable muscle contractions that may cause jerking or twisting of certain muscle groups)
dysphagia & dysarthria due to muscle groups involved in speech being involved
rigidity/stiffness of limbs
tremor
writhing movements
dementia
spasticity
weakness
seizures (rare)
toe walking
retinitis pigmentosa, another degenerative disease that affects the individual's retina, often causing alteration of retinal color and progressive deterioration of the retina at first causing night blindness and later resulting in a complete loss of vision.25% of individuals experience an uncharacteristic form of PKAN that develops post-10 years of age and follows a slower, more gradual pace of deterioration than those pre-10 years of age. These individuals face significant speech deficits as well as psychiatric and behavioral disturbances.Being a progressive, degenerative nerve illness, PKAN leads to early immobility and often death by early adulthood. Death occurs prematurely due to infections such as pneumonia, and the disease in itself is technically not life limiting. - Prognosis
- Survival rates for those diagnosed with typical PKAN, and left untreated is 11.18 years with a standard deviation of 7.8 years. A study reporting good outcomes in a single patient with late onset PKAN has been performed.
- Onset
- Pantothenate kinase-associated neurodegeneration (PKAN) typically has an onset in childhood, though it can also present in late adolescence or adulthood. The onset usually occurs between ages 3 and 10.
- Prevalence
- The prevalence of pantothenate kinase-associated neurodegeneration (PKAN) is estimated to be rare, affecting approximately 1 to 3 per million individuals worldwide.
- Epidemiology
- Prevalence data regarding this disorder remains incomplete, however it is estimated that anywhere between 1 in 1,000,000 to 3 in 1,000,000 individuals will be affected by this disorder (based upon observed cases in a population), but once again this is only an estimate as the disease is so rare it is difficult to statistically and accurately ascertain.
- Intractability
- Pantothenate kinase-associated neurodegeneration (PKAN) is generally considered intractable, as there is currently no cure for the disease. Treatment primarily focuses on managing symptoms and improving quality of life. Various interventions, such as medications, physical therapy, and possibly surgical options, are used to address specific symptoms, but they do not halt disease progression. Research is ongoing to find potential therapies.
- Disease Severity
- Pantothenate kinase-associated neurodegeneration (PKAN) is a severe form of neurodegeneration that often presents in childhood. The disease is characterized by progressive motor dysfunction, dystonia, spasticity, and parkinsonism. Severity varies, but many patients experience significant impairment in motor skills, speech, and cognitive functions, leading to considerable disability. The progression of symptoms can vary, with some individuals experiencing a rapid decline and others having a more gradual course. There is currently no cure, and treatment focuses on managing symptoms and improving quality of life.
- Healthcare Professionals
- Disease Ontology ID - DOID:3981
- Pathophysiology
- Pantothenate kinase-associated neurodegeneration (PKAN) is a form of neurodegeneration with brain iron accumulation (NBIA). The pathophysiology of PKAN involves mutations in the PANK2 gene, which encodes the enzyme pantothenate kinase 2. This enzyme is crucial in the coenzyme A (CoA) biosynthesis pathway. Deficiency or dysfunction of pantothenate kinase 2 leads to impaired CoA production, disrupting cellular metabolism, particularly in the nervous system. This disruption results in the abnormal accumulation of iron in the globus pallidus, a brain region rich in dopaminergic neurons, contributing to the progressive neurodegeneration and clinical manifestations of the disease.
- Carrier Status
- Pantothenate kinase-associated neurodegeneration (PKAN) is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disease. Carriers typically have one mutated copy and one normal copy of the gene and usually do not show symptoms of PKAN. However, they can pass the mutated gene to their offspring.
- Mechanism
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Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, inherited disorder characterized by progressive dystonia, Parkinsonism, and iron accumulation in the brain.
### Mechanism:
PKAN is primarily caused by mutations in the PANK2 gene, which encodes pantothenate kinase 2. This enzyme is crucial for the biosynthesis of coenzyme A (CoA) from pantothenic acid (vitamin B5).
### Molecular Mechanisms:
1. **Gene Mutation**: Mutations in PANK2 lead to reduced or nonfunctional pantothenate kinase 2 enzyme activity.
2. **Coenzyme A Biosynthesis**: The deficient activity of pantothenate kinase 2 disrupts the production of CoA, a vital cofactor in various biochemical pathways, including the metabolism of carbohydrates, fats, and proteins.
3. **Metabolic Dysfunction**: The lack of CoA results in metabolic imbalances and impaired energy production, which are essential for neuronal health.
4. **Iron Accumulation**: One of the hallmark features of PKAN is the abnormal accumulation of iron, particularly in the globus pallidus, a brain region involved in regulating voluntary movement. The connection between PANK2 dysfunction and iron accumulation is not fully understood, but it may involve dysregulated iron metabolism and oxidative stress.
5. **Neuronal Degeneration**: The scarcity of CoA and subsequent metabolic disturbances contribute to progressive neuronal degeneration and the clinical symptoms observed in PKAN, such as dystonia, parkinsonism, and cognitive decline.
Research continues to explore the detailed biochemical pathways affected by PANK2 mutations to better understand and potentially develop treatments for PKAN. - Treatment
- Phosphopantothenate has been shown to treat PKAN in a human, and also in a mouse model of the disease. Pantethine (a precursor of pantetheine) has been studied and shown to be effective in a mouse and in a fruit fly model of the disease.
- Compassionate Use Treatment
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Pantothenate kinase-associated neurodegeneration (PKAN) is a rare genetic disorder, and treatment options are often limited. Some experimental and compassionate use treatments include:
1. **Deferiprone**: An iron-chelating agent used off-label to reduce brain iron accumulation in PKAN patients.
2. **Pantothenate (Vitamin B5) and its derivatives**: Occasionally used in experimental settings to manage symptoms, though evidence of efficacy is limited.
3. **Deep Brain Stimulation (DBS)**: An experimental surgical intervention to alleviate dystonia and parkinsonism in PKAN patients.
4. **4’-Phosphopantetheine**: Being investigated as an experimental drug to bypass the metabolic block in PKAN.
5. **Supportive Therapies**: Including physical therapy, speech therapy, and occupational therapy to manage symptoms and improve quality of life.
Always consult with a healthcare professional for the most appropriate and updated treatment options. - Lifestyle Recommendations
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Lifestyle recommendations for Pantothenate Kinase-Associated Neurodegeneration (PKAN) generally focus on managing symptoms and improving quality of life, as there is no cure for the condition. Here are some strategies that can be helpful:
1. **Physical Therapy**: Regular physical therapy can help maintain mobility and muscle strength, reducing the severity of motor symptoms.
2. **Occupational Therapy**: This may assist with daily activities and promote independence.
3. **Speech Therapy**: Because PKAN can affect speech, working with a speech therapist might improve communication skills.
4. **Healthy Diet**: A balanced diet supports overall well-being and may help manage some symptoms.
5. **Exercise**: Gentle, regular exercise can help maintain physical function and overall health.
6. **Support Networks**: Connecting with support groups or counseling services can provide emotional support and practical advice.
It's important for patients and families to work closely with a healthcare team specialized in neurodegenerative diseases to tailor these recommendations to individual needs. - Medication
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Pantothenate kinase-associated neurodegeneration (PKAN) is a rare genetic disorder. Management often involves symptomatic treatment rather than disease-specific medication. Medications used may include:
- Baclofen or diazepam for muscle spasticity
- Anticholinergic drugs for dystonia
- Antidepressants for mood disorders
- Botulinum toxin injections for focal dystonia
Chelation therapy with deferiprone or deferoxamine has been explored to reduce brain iron accumulation, although its efficacy is still under investigation. Treatment plans should be closely monitored by a healthcare professional. - Repurposable Drugs
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For pantothenate kinase-associated neurodegeneration (PKAN), some repurposable drugs include:
1. **Deferiprone (iron chelator)**: Decreases iron accumulation in the brain.
2. **Pantothenate (Vitamin B5)**: Supplementation to support metabolic processes, though evidence is limited.
3. **Coenzyme A precursors**: To support the metabolic pathway affected by the disease.
Despite these options, there is no definitive cure, and treatments primarily aim to manage symptoms and improve quality of life. - Metabolites
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Pantothenate kinase-associated neurodegeneration (PKAN) is a rare genetic disorder characterized by the accumulation of iron in the brain. It involves a mutation in the PANK2 gene, which is crucial for the metabolism of coenzyme A.
Primary metabolic changes associated with PKAN include:
1. **Pantothenate (Vitamin B5):** Due to defective pantothenate kinase, the conversion of pantothenate to 4'-phosphopantothenate is impaired.
2. **Coenzyme A (CoA):** Reduced levels of CoA, leading to impaired energy production and lipid metabolism.
3. **Iron:** Abnormal accumulation in the globus pallidus region of the brain.
There is no specific mention of "nan" (which could mean different things such as nanomolar concentration, nanoparticle, or not a number) in the direct relation to the disease’s metabolic profile, so more context would be needed for precise information related to "nan." - Nutraceuticals
- Pantothenate kinase-associated neurodegeneration (PKAN) is a rare genetic disorder that affects the nervous system. Currently, there is no cure for PKAN, but some patients may consider the use of nutraceuticals as part of their management strategy. Nutraceuticals like coenzyme Q10, vitamin E, and pantothenic acid (vitamin B5) are sometimes used in hopes of providing neuroprotection or supporting general health, though their efficacy specifically for PKAN is not well-established. It is important to consult with a healthcare professional before starting any new supplements.
- Peptides
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Pantothenate kinase-associated neurodegeneration (PKAN) is a rare genetic disorder characterized by the accumulation of iron in the brain, particularly in the basal ganglia. This can lead to a variety of neurological symptoms, including movement disorders, dystonia, and cognitive decline.
Currently, there are no specific peptide-based treatments or nanotechnology applications that have been widely adopted for PKAN. Research in these areas may be ongoing, but standard care primarily focuses on symptom management through medications, physical therapy, and other supportive measures.