Pantothenate Kinase-Associated Neurodegeneration

Pantothenate kinase-associated neurodegeneration (PKAN) is a progressive neurodegenerative disorder characterized by iron accumulation in the basal ganglia, primarily the globus pallidus and substantia nigra. The underlying cause is mutations in the PANK2 gene, which encodes pantothenate kinase, an enzyme crucial for coenzyme A synthesis. The resulting metabolic dysfunction leads to mitochondrial impairment and oxidative stress, contributing to neuronal damage. Clinically, PKAN presents with a range of motor symptoms, including dystonia, rigidity, choreoathetosis, and spasticity. Ocular manifestations, such as retinal degeneration and optic atrophy, are also common. Cognitive and behavioral abnormalities can further complicate the clinical picture. Diagnosis relies on clinical findings, MRI demonstrating the characteristic 'eye-of-the-tiger' sign, and genetic confirmation of PANK2 mutations. Management is primarily symptomatic, involving medications to alleviate dystonia, physical and occupational therapy to maintain function, and speech therapy to address communication and swallowing difficulties. Experimental therapies, such as iron chelators and gene therapy, are under investigation.