Abstract Details

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

Topic Movement Disorders

Presentation(s) P04 - (-)

Poster/Presentation
Number 158

Objective

Background 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 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 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 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.

Authors/Disclosures
Federico E. Micheli, MD PRESENTER	No disclosure on file
Claudia Perandones	No disclosure on file
Juan C. Giugni, MD (University of Florida College of Medicine)	No disclosure on file
Patricia K. Coyle, MD, FAAN (SUNY At Stony Brook)	Dr. Coyle has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Accordant. Dr. Coyle has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Coyle has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Sanofi Genzyme. Dr. Coyle has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Coyle has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GlaxoSmithKline. Dr. Coyle has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon Therapeutics. The institution of Dr. Coyle has received research support from CorEvitas LLC. The institution of Dr. Coyle has received research support from Genentech/Roche. The institution of Dr. Coyle has received research support from NINDS. The institution of Dr. Coyle has received research support from Sanofi Genzyme. The institution of Dr. Coyle has received research support from Cleveland Clinic.
	No disclosure on file
Gabriela Raina	No disclosure on file
Luis Pellene	Luis Pellene has nothing to disclose.
	No disclosure on file
	No disclosure on file

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