Is Progressive Supranuclear Palsy Part of the Phenotypic Spectrum of Niemann-Pick Disease Type C?

FEDERICO MICHELI; PERANDONES CLAUDIA; GIUNI JC; GABRIELA GONZALEZ-ALEMAN; GABRIELA BEATRIZ RAINA; LUIS PELLENE; BRUNI NICOLAS; RADRIZZANI M

San Diego, CA

Congreso; 65th American Academy of Neurology Anual Meeting 2013; 2013

American Academy of Neurology

OBJETIVE: To establish whether four patients who had been diagnosed with progressive supranuclear palsy (PSP) might exhibit lipid trafficking abnormalities, and therefore might actually represent cases of misdiagnosed late-onset Niemann-Pick disease type C (NP-C). BACKGROUND: PSP is a progressive neurodegenerative disease characterized by gait disturbance, vertical supranuclear gaze palsy (VSGP), akinetic-rigid syndrome with levodopa unresponsiveness, frontotemporal dementia and premature death. Adult-onset NP-C has several symptoms in common with PSP, but is an underestimated pathology due to its highly variable clinical phenotype and age of onset. We have examined impaired intracellular lipid trafficking defects among four patients diagnosed with PSP. DESIGN/METHODS: Detailed information from patient medical histories was collected that related to the timing of neurological disease onset, the type and severity of neurological signs and symptoms, psychiatric disorders, diagnosis and treatment. Skin biopsies were taken from patients displaying parkinsonism when VSGP became evident. Filipin staining was performed as described previously on skin fibroblasts from each patient, following culture in an LDL-enriched medium. All filipin staining analyses included both positive controls and negative controls. RESULTS: All four patients exhibited a biochemical phenotype consistent with a diagnosis of NP-C, as confirmed by filipin staining in cultured skin fibroblasts. Molecular studies of the four patients searching for mutations in NPC1 or NPC2 gene are still on going. CONCLUSIONS: These observations suggest that it might be pertinent to investigate whether PSP could possibly represent part of the phenotypic spectrum of NP-C, despite the fact that NP-C has a well characterised mutational genetic origin while only genetic loci associated with an increased risk of PSP have so far been identified. A step toward answering this question would be to define any homeostatic alterations in cholesterol or other lipid metabolism in PSP in order to establish whether there are underlying biochemical mechanisms held in common between PSP and NP-C. Supported by: National Research Council of Argentina (CONICET)and the National University of San Martín (UNSAM).