Pantothenate kinase-associated neurodegeneration (PKAN) is a hereditary progressive disorder and the most frequent form of
neurodegeneration with brain iron accumulation (NBIA). PKAN patients present with a progressive
movement disorder,
dysarthria,
cognitive impairment and
retinitis pigmentosa. In magnetic resonance imaging, PKAN patients exhibit the pathognonomic "eye of the tiger" sign in the globus pallidus which corresponds to
iron accumulation and
gliosis as shown in neuropathological examinations. The discovery of the disease causing mutations in PANK2 has linked the disorder to
coenzyme A (
CoA) metabolism. PANK2 is the only one out of four PANK genes encoding an
isoform which localizes to mitochondria. At least two other NBIA genes (PLA2G6, C19orf12) encode
proteins that share with PANK2 a mitochondrial localization and all are suggested to play a role in
lipid homeostasis. With no causal
therapy available for PKAN until now, only symptomatic treatment is possible. A multi-centre retrospective study with bilateral pallidal
deep brain stimulation in patients with NBIA revealed a significant improvement of
dystonia. Recently, studies in the PANK Drosophila model "fumble" revealed improvement by the compound
pantethine which is hypothesized to feed an alternate
CoA biosynthesis pathway. In addition, pilot studies with the
iron chelator deferiprone that crosses the blood brain barrier showed a good safety profile and some indication of efficacy. An adequately powered randomized clinical trial will start in 2012. This review summarizes clinical presentation, neuropathology and pathogenesis of PKAN.