A Case of Pantothenate Kinase-Associated Neurodegeneration (PKAN) in a Patient with One Known Pathologic Variant and One Variant of Unknown Significance (P11-4.006)

Abstract

<h3>Objective:</h3> Raise interest in the possibility of an unidentified PANK2 gene mutation in the pathogenesis of PKAN <h3>Background:</h3> Pantothenate kinase-associated neurodegeneration (PKAN), previously known as Hallervorden-Spatz Disease, is a neurodegenerative disorder associated with brain iron deposition. PKAN follows an autosomal recessive inheritance pattern and presents in childhood (classical) or around the second decade of life (atypical). Individuals with PKAN typically present with dysarthria, dystonia, speech difficulties, and extrapyramidal symptoms. PKAN has a characteristic “eye of the tiger” sign on MRI with hypointensity of the globus pallidus surrounded by an area of hyperintensity. Pantothenate kinase 2 (PANK2) gene sequencing changes have been identified as markers of PKAN. <h3>Case Description:</h3> The patient discussed is a 27-year-old woman who presented in 2013 for abnormal posturing and cramping of her hands and feet since she was four. Based on the patient’s physical exam, it was believed she was suffering from young-onset Parkinson’s disease or dystonia. However, a trial of Levodopa resulted in no improvement, genetic testing for dystonia was negative, and her brain MRI was read as normal. Due to worsening symptoms, her MRI was reassessed, and the subtle “eye of the tiger” sign was recognized. Further genetic testing showed she was a carrier for two heterozygous PANK2 mutations, one known pathologic variant and one unknown. The patient elected to join a clinical trial as her symptoms progressed. Nine years since presenting, she has completed two clinical trials and is currently on Deferiprone (an iron chelator), Artane, and Baclofen for symptom management. <h3>Design/Methods:</h3> NA <h3>Results:</h3> NA <h3>Conclusions:</h3> This report discusses a patient with PKAN who has one PANK2 mutation of known significance and one unknown variant. Considering PKAN is an autosomal recessive disease, this report suggests a novel PANK2 pathogenic variant. This study also demonstrates how the diagnosis of PKAN can be easily missed due to subtle MRI changes. <b>Disclosure:</b> Dr. Cevallos has nothing to disclose. Miss Rubin has nothing to disclose. Miss Rhinehart has nothing to disclose. Dr. Houghton has nothing to disclose.