Positive filipin staining in patients with progressive supranuclear palsy: Expanding the phenotypic spectrum of Niemann-Pick disease type C?

GIUGNI JC; MICHELI FE; PERANDONES CLAUDIA; GABRIELA BEATRIZ RAINA; PELLENE LA; CALVO DS; GONZALEZ ALEMAN G; BRUNI NICOLAS; FARINI VERÓNICA L; RADRIZZANI M

Sydney

Congreso; The MDS 17th International Congress of Parkinson's Disease and Movement Disorders; 2013

Movement Disorders Society

Objective:  To establish whether patients who had 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 and dementia. Adult-onset NP-C has 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 in fourteen patients diagnosed with PSP. Methods: Detailed information including the timing of neurological disease onset, the type and severity of neurological signs and symptoms has been collected. 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 and negative controls. Results: Ten out of fourteen 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 patients searching for mutations in the NPC1 or NPC2 genes are still on going. Conclusions: These findings 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-characterized mutational genetic origin while only genetic loci associated with an increased risk of PSP have so far been identified. Further studies are needed to clarify the etiological link between PSP and NP-C.