pantothenate kinase-associated neurodegeneration

Pantothenate kinase-associated neurodegeneration (PKAN) is a neurological disorder in which excess iron builds up in specific brain regions, leading to problems with movement and other nervous-system functions. It is caused by changes in the PANK2 gene, which encodes an enzyme needed for producing coenzyme A, a molecule essential for normal cell metabolism. Symptoms usually begin in childhood, although onset can range from late infancy to the teen years, and both boys and girls are affected. PKAN is considered rare, affecting roughly one to nine people in every million. Because it progresses over time, early recognition and coordinated care are important for maintaining quality of life.

PKAN primarily presents with neurological features. Early signs often include difficulty coordinating movements and an unusual, stiff gait. Brain imaging typically reveals the so-called “eye-of-the-tiger” appearance in the globus pallidus, a finding considered characteristic of this condition. As the disorder evolves, many individuals develop involuntary muscle contractions (dystonia), rigidity, chorea, and choreoathetosis, which together can greatly affect mobility and speech. Seizures, elevated muscle-enzyme levels in blood tests, and progressive speech difficulties (dysarthria) are also frequent. Cognitive and behavioral changes may emerge over time. Some individuals experience dementia, obsessive-compulsive traits, or other forms of mental deterioration, reflecting deeper neurological involvement. A subset lose the ability to walk independently, and swallowing problems can lead to nutritional challenges. Less common features include pigmentary retinopathy that may affect vision, tremor, tics, and spasticity. Not all individuals experience every feature, and severity varies considerably. Because the condition can involve multiple body systems, families may encounter new concerns as the child grows, underscoring the importance of ongoing neurological, cognitive, and general medical monitoring.

PKAN results from pathogenic variants in the PANK2 gene. The PANK2 enzyme starts the first step in producing coenzyme A; when the enzyme is disrupted, iron and other metabolites accumulate in brain tissue and cause the neurological symptoms described. The disorder is inherited in an autosomal recessive pattern, meaning a child must receive one altered copy of PANK2 from each parent to be affected. Parents who each carry one altered copy (carriers) are typically healthy but have a 25 percent chance with every pregnancy of having a child with PKAN. The condition is more common when parents share a common ancestor because they are more likely to carry the same rare variant. Carrier testing and genetic counseling can help extended family members understand their own risks and make informed family-planning decisions.

Currently, management focuses on supportive care and symptom control through a multidisciplinary approach. Physical and occupational therapy help maintain mobility and reduce contractures, while speech and feeding specialists address communication and swallowing issues. Medications chosen by a neurologist can lessen dystonia, rigidity, or seizures, and some individuals benefit from assistive devices to improve daily functioning. Regular surveillance by neurology, rehabilitation, nutrition, and ophthalmology teams helps identify emerging complications early. Because PKAN affects several body systems and needs change over time, coordinated care in centers familiar with complex movement disorders is recommended. Genetic counseling provides ongoing support for families as they consider future pregnancies or testing of siblings.

PKAN is generally progressive, but the rate and pattern of progression differ greatly among individuals. Some children experience rapid loss of motor skills in the first decade of life, whereas others retain walking ability and speech into adolescence or adulthood. Cognitive decline and movement-related complications can limit independence, yet proactive therapy, nutritional support, and adaptive equipment often improve day-to-day functioning. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with neurologists and rehabilitation specialists experienced in movement disorders, and to work with genetic counselors who can guide long-term planning and offer psychosocial resources.

Several clinical trials are currently investigating new treatments aimed at reducing iron accumulation or modifying disease pathways. Individuals interested in participating can search ClinicalTrials.gov or discuss eligibility with their healthcare team.