Summary about Disease
Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, inherited neurological disorder characterized by progressive movement difficulties and other neurological problems. It is caused by mutations in the PANK2 gene, which is responsible for producing an enzyme crucial for the metabolism of vitamin B5 (pantothenate). This metabolic dysfunction leads to iron accumulation in the brain, specifically in the basal ganglia, resulting in progressive neurodegeneration. PKAN falls under a larger group of disorders called Neurodegeneration with Brain Iron Accumulation (NBIA).
Symptoms
PKAN symptoms vary in severity and age of onset. There are generally two forms: classical and atypical.
Classical PKAN: Onset typically occurs in early childhood (before age 6). Symptoms include:
Progressive dystonia (involuntary muscle contractions causing twisting and repetitive movements)
Rigidity
Choreoathetosis (involuntary jerky movements)
Spasticity
Speech difficulties (dysarthria)
Swallowing difficulties (dysphagia)
Vision problems (retinitis pigmentosa, optic atrophy)
Cognitive decline (eventually)
Atypical PKAN: Onset is later in childhood or adulthood. Progression is slower, and symptoms may include:
Speech problems
Psychiatric problems (depression, anxiety, obsessive-compulsive disorder)
Motor problems like gait disturbances or balance issues
Dystonia (less severe than classical form)
Parkinsonism
Cognitive Decline
Causes
PKAN is caused by mutations in the PANK2 gene. This gene provides instructions for making pantothenate kinase 2, an enzyme involved in the first step of coenzyme A (CoA) biosynthesis. CoA is essential for many metabolic processes in the body. *PANK2* mutations lead to a deficiency in this enzyme, disrupting CoA production and causing an accumulation of cysteine-containing compounds that bind to iron, leading to iron accumulation in the brain (specifically the globus pallidus and substantia nigra). PKAN is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
There is no cure for PKAN, and treatment focuses on managing symptoms. Medications used include:
Baclofen, tizanidine, trihexyphenidyl, or other anticholinergics: To reduce muscle spasticity and dystonia.
Botulinum toxin injections: To treat focal dystonia.
Iron chelators (e.g., deferiprone): To reduce iron accumulation in the brain (effectiveness is still under investigation).
Antidepressants, anxiolytics, or antipsychotics: To manage psychiatric symptoms.
Levodopa: May be used to address parkinsonism if present. Other Supportive therapies:
Physical therapy: To maintain mobility and prevent contractures.
Occupational therapy: To assist with daily living activities.
Speech therapy: To improve speech and swallowing difficulties.
Nutritional support: To ensure adequate nutrition and prevent malnutrition.
Deep brain stimulation (DBS): In some cases, DBS may be considered to reduce dystonia (more commonly considered in atypical PKAN).
Is Communicable
No, PKAN is not communicable. It is a genetic disorder caused by a mutation in the PANK2 gene and is inherited, not infectious.
Precautions
There are no specific precautions to prevent PKAN, as it is a genetic disorder. Genetic counseling is recommended for families with a history of PKAN who are planning to have children. This can help assess the risk of having a child with the condition.
How long does an outbreak last?
PKAN is not an infectious disease and does not have outbreaks. It is a chronic, progressive condition that lasts throughout the affected individual's life. Symptom progression varies, but the condition is generally lifelong.
How is it diagnosed?
Diagnosis of PKAN typically involves:
Clinical Evaluation: Neurological examination to assess symptoms and signs.
Brain MRI: MRI can reveal characteristic iron accumulation in the globus pallidus (an area of the brain involved in motor control), creating a "tiger eye" sign which is highly suggestive of PKAN.
Genetic Testing: PANK2 gene sequencing to identify mutations. This is the definitive diagnostic test.
Eye Examination: To check for retinitis pigmentosa or optic atrophy.
Timeline of Symptoms
The timeline of symptoms varies depending on whether it is the classical or atypical form.
Classical PKAN:
Early Childhood (before age 6): Initial motor problems (e.g., gait disturbances, clumsiness), dystonia, rigidity.
Childhood/Adolescence: Progression of motor symptoms, speech difficulties, swallowing difficulties, vision problems, cognitive decline may become noticeable.
Atypical PKAN:
Later Childhood/Adolescence/Adulthood: Onset of psychiatric problems (depression, anxiety, OCD), speech problems, gait disturbances, balance issues, slower progression of dystonia (if present), parkinsonism, and gradual cognitive decline. The rate of progression varies greatly from individual to individual.
Important Considerations
Genetic Counseling: Important for families with a history of PKAN.
Early Diagnosis: Early diagnosis allows for timely initiation of symptomatic treatment and supportive care.
Multidisciplinary Approach: Management requires a multidisciplinary team, including neurologists, geneticists, physical therapists, occupational therapists, speech therapists, and mental health professionals.
Research: Ongoing research is focused on developing new treatments, including gene therapy.
Support Groups: Support groups for patients and families can provide valuable emotional support and resources.
Differential Diagnosis: It is important to rule out other forms of NBIA and other neurological disorders that can mimic PKAN.