Case Report
Piradee Suwanpakdee, Napakjira
Abstract
Background: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare neurodegenerative disorder that occurs due to autosomal recessive mutations in the PANK2 gene. Several of these pathogenic mutations have been identified, and ethnic differences seem to play an important role in the clinical outcomes of this disease. Methods and Findings: Herein we present two Thai patients diagnosed with classic PKAN. The patients presented with typical features of progressive dystonia and an “eye-of-the-tiger” signal on their brain MRIs. Molecular analysis of the PANK2 gene was, therefore, performed to study the mechanism underlying this disease state. Clinically, we observed features of generalized dystonia and dysarthria during early childhood in both patients. Brain MRIs showed a central hyperintensity surrounded by a region of hypointensity in the globus pallidus which are hallmarks of this disease. Upon molecular analysis, we identified two missense mutations: c.1475C>T (p.Ala492Val) and c.1103A>G (p.Asp368Gly) and one splice site mutation: c.982-1G>C (IVS2-1G>C) in the PANK2 gene. Interestingly, the c.982-1G>C intronic mutation has previously been reported in only one Thai patient with classic PKAN. Conclusion: Our study demonstrates the clinical and genetic characteristics of classic PKAN in two Thai patients. Generalized dystonia and dysarthria were the main clinical features that differed from classic PKAN in Caucasians. Two unique missense mutations and one recurrent splice-site mutation were identified in Thai patients with classic PKAN.