Pantothenate kinase–associated neurodegeneration (PKAN)

Causes and genetics

PKAN is caused by mutations in the PANK2 gene, which encodes an enzyme involved in coenzyme A biosynthesis. The disorder is usually inherited in an autosomal recessive pattern, meaning affected individuals typically have two altered copies of the gene. The genetic defect is believed to interfere with normal cellular metabolism, leading to abnormal iron handling and deposition in specific regions of the brain.

Clinical features

Symptoms vary with disease onset and individual course but commonly include movement abnormalities and cognitive changes. Typical manifestations can include:

• Dystonia: sustained or intermittent muscle contractions causing twisting movements or abnormal postures.
• Parkinsonism: slowness of movement, rigidity and gait difficulty.
• Spasticity and dysarthria: stiff muscles and speech impairment.
• Cognitive decline: attention, memory and executive function may be affected.

Some patients also experience visual impairment, behavioral symptoms or seizures. For further general information, see resources on rare neurodegenerative diseases.

Diagnosis and imaging

Diagnosis combines clinical evaluation, family history and genetic testing for PANK2 mutations. Brain magnetic resonance imaging (MRI) often shows characteristic iron accumulation, particularly in the globus pallidus. A distinctive pattern known as the "eye of the tiger" sign—central hyperintensity surrounded by hypointense iron deposition on certain MRI sequences—is frequently cited in descriptions of PKAN, though imaging must be interpreted with clinical and genetic data. For imaging references, consult radiology resources.

Management and prognosis

There is no cure for PKAN; treatment is symptomatic and multidisciplinary. Management strategies focus on improving quality of life and may include:

• Oral medications to reduce dystonia or Parkinson-like symptoms.
• Physical, occupational and speech therapy for mobility and communication.
• Orthopedic interventions and assistive devices to maintain function.
• In selected cases, neurosurgical approaches such as deep brain stimulation have been used to treat severe dystonia.

Experimental treatments, including iron-chelating agents and approaches targeting metabolic pathways, have been explored; results are mixed and such therapies remain under investigation. For clinical trials and emerging therapies, see research and treatment information.

History and nomenclature

The disorder was historically referred to by an eponym that has fallen out of favor; the current preferred name reflects the underlying enzyme defect. Contemporary practice emphasizes genetic diagnosis and ethically neutral terminology. For broader context about NBIA disorders, a general overview is available at related disease summaries.

Because PKAN is rare and heterogeneous, individuals and families are usually advised to seek care from specialized centers with experience in movement disorders and genetic neurology. Genetic counseling is recommended for affected families to discuss inheritance, testing and family planning options.