Atypical pantothenate kinase-associated neurodegeneration

Atypical pantothenate kinase-associated neurodegeneration (atypical PKAN) is a rare inherited neurodegenerative disorder that represents the later-onset, more slowly progressive form of pantothenate kinase-associated neurodegeneration (formerly known as Hallervorden-Spatz syndrome). It is caused by mutations in the PANK2 gene, which encodes the enzyme pantothenate kinase 2, essential for coenzyme A biosynthesis. The disease belongs to the group of neurodegeneration with brain iron accumulation (NBIA) disorders, characterized by abnormal iron deposition in the basal ganglia, particularly the globus pallidus. A hallmark neuroimaging finding is the "eye-of-the-tiger" sign on brain MRI, though this may be less consistently present in atypical cases. Unlike the classic form of PKAN, which typically presents in early childhood with rapid progression, atypical PKAN generally has onset in the second or third decade of life, though onset can range from late childhood into adulthood. Key clinical features include progressive dystonia, dysarthria (speech difficulties), psychiatric symptoms (such as depression, emotional lability, and personality changes), and cognitive decline. Patients may also develop spasticity, parkinsonism, and gait difficulties. Retinitis pigmentosa, which is common in classic PKAN, is less frequently observed in the atypical form. Psychiatric and behavioral symptoms may be prominent early features, sometimes leading to initial misdiagnosis. There is currently no cure or disease-modifying treatment for atypical PKAN. Management is symptomatic and supportive, focusing on alleviating dystonia with medications such as baclofen, trihexyphenidyl, or botulinum toxin injections. Deep brain stimulation (DBS) of the globus pallidus internus has been used in some patients with medically refractory dystonia, with variable results. Physical therapy, speech therapy, and occupational therapy are important components of multidisciplinary care. Iron chelation therapy with deferiprone has been investigated in clinical trials, though its efficacy remains under evaluation. Genetic counseling is recommended for affected families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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