Siblings with the adult-onset slowly progressive type of pantothenate kinase-associated neurodegeneration and a novel mutation, Ile346Ser, in PANK2: Clinical features and 99mTc-ECD brain perfusion SPECT findings

Abstract Pantothenate kinase-associated neurodegeneration (PKAN), formerly known as Hallervorden–Spatz syndrome (HSS), is an autosomal recessive neurodegenerative disorder characterized by iron accumulation in the brain. Mutations in the pantothenate kinase 2 ( PANK2 ) gene are known to be responsible for PKAN. Several studies have revealed correlations between clinical phenotypes and particular PANK2 mutations. The adult-onset slowly progressive type of PKAN with PANK2 mutations is very rare. In this report, we describe siblings with the adult-onset slowly progressive type of PKAN with a novel mutation, Ile346Ser, in PANK2 . The siblings had the same mutation in PANK2 and had common clinical signs such as misalignment of teeth, a high arched palate, hollow feet, a slight cognitive decline, and an apparent executive dysfunction, although they showed different patterns of movement disorders. Thus, even if PKAN patients have identical mutations, it is likely that they will present with different types of movement disorders. Brain perfusion single photon emission computed tomography in both patients showed decreased regional cerebral blood flow in the bilateral frontoparietal lobes, the globus pallidus, the striatum, and around the ventriculus quartus. Cardiac uptake of [ 123 I] meta-iodobenzylguanidine was normal in both patients. Analysis of genotype–phenotype correlations and the elucidation of mutational effects on pantothenate kinase 2 function, expression, and structure are important for understanding the mechanisms of PKAN.