Pantothenate kinase-associated neurodegeneration

Pantothenate kinase-associated neurodegeneration (PKAN), formerly known as Hallervorden-Spatz syndrome or neurodegeneration with brain iron accumulation type 1 (NBIA1), is a rare inherited neurodegenerative disorder characterized by progressive iron accumulation in the brain, particularly in the globus pallidus and substantia nigra. It is the most common form of neurodegeneration with brain iron accumulation (NBIA). PKAN is caused by mutations in the PANK2 gene, which encodes the enzyme pantothenate kinase 2, essential for coenzyme A biosynthesis. Deficiency of this enzyme leads to abnormal iron deposition in the basal ganglia, resulting in progressive damage to the nervous system. PKAN presents in two main forms: classic and atypical. The classic form typically begins in early childhood (before age 6) and is characterized by progressive dystonia, dysarthria, rigidity, and gait difficulties. Pigmentary retinopathy is common in the classic form. The atypical form has a later onset, usually in the second or third decade of life, and tends to progress more slowly, often presenting with speech difficulties, psychiatric symptoms, and cognitive decline. A hallmark neuroimaging finding on brain MRI is the "eye-of-the-tiger" sign — a central hyperintensity surrounded by a ring of hypointensity in the globus pallidus on T2-weighted images — which is highly suggestive of PKAN. There is currently no cure or disease-modifying treatment for PKAN. Management is symptomatic and supportive, focusing on alleviating dystonia and spasticity through medications such as baclofen (oral or intrathecal), trihexyphenidyl, and benzodiazepines. Deep brain stimulation (DBS) of the globus pallidus internus has been used in some patients with severe dystonia, with variable results. Iron chelation therapy with deferiprone has been investigated in clinical trials, with some evidence suggesting it may reduce brain iron levels, though its clinical benefit remains under study. Physical therapy, occupational therapy, and speech therapy are important components of ongoing care. Nutritional support may be needed as the disease progresses and swallowing becomes impaired.

Common questions about Pantothenate kinase-associated neurodegeneration