Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive condition caused by mutations in the PANK2 gene. Mutations in this gene lead to an inborn vitamin B5 metabolic disorder. Vitamin B5 is required to produce coenzyme A in cells, disruption of which can lead to the accumulation of harmful compounds in the brain, including iron. PKAN is the most common of the NBIA, or neurodegeneration with brain iron accumulation, disorders. NBIA disorders are marked by progressively abnormal involuntary movements and muscle tone and postural disturbances, which radiographically demonstrate evidence of iron accumulation in the brain. The “eye-of-the-tiger” sign indicates accumulation of iron in the brain in a characteristic pattern upon MRI and is considered diagnostic for PKAN.
Symptoms can vary markedly from case to case but typically disease extends over several years, leading to death in childhood or early adulthood in the classic scenario. Some deteriorate quickly and die within 1 to 2 years. Others deteriorate more slowly and some can plateau for long periods and continue to function into their thirties. Atypical patients often retain high functionality into later adulthood and some live into their sixties and seventies.
There is no cure for PKAN itself and treatment generally focuses on symptomatic therapies to palliate the numerous complications these patients experience. Attempts at treatment, such as chelation therapy, often lead to iron deficiencies before clinical neurologic benefit is achieved. A small phase II pilot study using deferiprone (Ferriprox), however, has rejuvenated interest in chelation and demonstrated a statistically significant reduction in iron in the brain. Clinical status remained unchanged, but researchers think a longer trial may produce clinical benefit. A phase III study is underway.
Contributed by William Yarnall, RPh, CCP