{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T16:05:19Z","timestamp":1794067519850,"version":"4.8.0"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>(1) Background: Niemann\u2013Pick type C1 (NP-C1) is a lysosomal storage disorder that results in the defective trafficking of cholesterol and other cellular lipids in the endosomal\u2013lysosomal pathway. This rare autosomal recessive disorder presents in three forms based on the age of onset. The adult form presents in patients greater than 15 years of age but is rarely seen after the age of 30. Common symptoms of the late adult-onset category of NP-C1 include progressive cognitive impairment and ataxia, with psychiatric and movement disorders presenting less frequently than in other forms of NP-C1. Dystonic movement disorders present most frequently, along with chorea, myoclonus, and parkinsonism. Herein, we present a rare case of NP-C1, diagnosed at age 35 with an initial symptom of supranuclear palsy. The goal of the presented case is to highlight the importance of the neurological examination and an inclusive differential diagnosis in patients with new-onset supranuclear palsy. (2) Methods: A single case report. (3) Results: A 46-year-old male with a past medical history of NP-C1 was admitted to the hospital for respiratory distress. He was noted to have a supranuclear gaze palsy with partially preserved voluntary saccades to the right. His mother revealed that he first had difficulty moving his eyes at the age of 34. After multiple consultations and genetic testing one year later, he was diagnosed with NP-C1. (4) Conclusions: Because NP-C1 affects many regions of the brain responsible for eye movements, neurological eye assessments can be a useful tool in diagnoses. Furthermore, eye movement abnormalities may be the initial presenting symptom of NP-C1, predisposing patients to misdiagnosis with progressive supranuclear palsy and other conditions that may mimic early-stage NP-C1. Definitive diagnosis is achieved through genetic testing. Filipin staining test was the gold standard in the past. The NP-C Suspicion Index was developed to assist in diagnoses, but its efficacy is unclear with late adult-onset NP-C1. Although no cure exists, early identification can facilitate an improved symptom management course for patients. Miglustat, a glucosylceramide synthase (GCS) inhibitor, is the approved therapy in Europe specific to NP-C1 for slowing and preventing the neurological manifestations of NP-C1. Delays between symptom onset and treatment initiation are likely to result in poorer outcomes and a progression of neurological symptoms. High doses may present tolerance concerns, especially in cases of delayed treatment and advanced neurological deficit.<\/jats:p>","DOI":"10.3390\/neurolint16030042","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T06:59:32Z","timestamp":1715756372000},"page":"561-566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Supranuclear Palsy as an Initial Presentation of the Adult-Onset Niemann-Pick Type C"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0977-0365","authenticated-orcid":false,"given":"Ali A.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5228-4303","authenticated-orcid":false,"given":"Willy","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL 33431, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Babici","sequence":"additional","affiliation":[{"name":"Department of Neurology, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL 33431, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Hagan","sequence":"additional","affiliation":[{"name":"Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Wald","sequence":"additional","affiliation":[{"name":"Department of Neurology, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL 33431, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Swerdloff","sequence":"additional","affiliation":[{"name":"Department of Neurology, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL 33431, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13023-018-0785-7","article-title":"Consensus clinical management guidelines for Niemann-Pick disease type C","volume":"13","author":"Geberhiwot","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1212\/CPJ.0000000000000399","article-title":"Recommendations for the detection and diagnosis of Niemann-Pick disease type C: An update","volume":"7","author":"Patterson","year":"2017","journal-title":"Neurol. Clin. Prac."},{"key":"ref_3","first-page":"120","article-title":"The adult form of Niemann-Pick disease type C","volume":"130","author":"Lesca","year":"2007","journal-title":"Brain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1212\/WNL.0b013e3182563b82","article-title":"Development of a Suspicion Index to aid diagnosis of Niemann-Pick disease type C","volume":"78","author":"Wijburg","year":"2012","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1001\/archopht.1981.03930020676010","article-title":"Ocular Motor Signs in Some Metabolic Diseases","volume":"99","author":"Cogan","year":"1981","journal-title":"Arch. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1007\/s00415-014-7385-9","article-title":"Central ocular motor disorders, including gaze palsy and nystagmus","volume":"261","author":"Strupp","year":"2014","journal-title":"J. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1007\/s10072-012-1155-1","article-title":"Vertical supranuclear gaze palsy in Niemann-Pick type C disease","volume":"33","author":"Salsano","year":"2012","journal-title":"Neurol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40035-019-0160-1","article-title":"How to spot ocular abnormalities in progressive supranuclear palsy? A practical review","volume":"8","author":"Phokaewvarangkul","year":"2019","journal-title":"Transl. Neurodegener."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1002\/ana.410400630","article-title":"The \u201cround the houses\u201d sign in progressive supranuclear palsy","volume":"40","author":"Quinn","year":"1996","journal-title":"Ann. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1097\/WCO.0b013e32833be924","article-title":"Neuropathology of variants of progressive supranuclear palsy","volume":"23","author":"Dickson","year":"2010","journal-title":"Curr. Opin. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S34","DOI":"10.1016\/j.parkreldis.2015.09.041","article-title":"The phenotypic spectrum of progressive supranuclear palsy","volume":"22","author":"Respondek","year":"2016","journal-title":"Park. Relat. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/mds.26512","article-title":"Environmental and occupational risk factors for progressive supranuclear palsy: Case-control study","volume":"31","author":"Litvan","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1212\/WNL.47.1.148","article-title":"Follow-up study of risk factors in progressive supranuclear palsy","volume":"47","author":"Golbe","year":"1996","journal-title":"Neurology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1212\/WNL.38.7.1031","article-title":"Prevalence and natural history of progressive supranuclear palsy","volume":"38","author":"Golbe","year":"1988","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1194\/jlr.M200203-JLR200","article-title":"Niemann-Pick type C disease: Mutations of NPC1 gene and evidence of abnormal expression of some mutant alleles in fibroblasts","volume":"43","author":"Tarugi","year":"2002","journal-title":"J. Lipid Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1007\/s11011-019-00445-w","article-title":"Laboratory diagnosis of the Niemann-Pick type C disease: An inherited neurodegenerative disorder of cholesterol metabolism","volume":"34","author":"Sitarska","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/bs.mcb.2014.10.028","article-title":"Laboratory diagnosis of Niemann-Pick disease type C: The filipin staining test","volume":"126","author":"Vanier","year":"2015","journal-title":"Methods Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.cca.2014.07.010","article-title":"A new simple and rapid LC-ESI-MS\/MS method for quantification of plasma oxysterols as dimethylaminobutyrate esters. Its successful use for the diagnosis of Niemann-Pick type C disease","volume":"437","author":"Boenzi","year":"2014","journal-title":"Clin. Chim. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ymgme.2012.03.012","article-title":"Recommendations for the diagnosis and management of Niemann-Pick disease type C: An update","volume":"106","author":"Patterson","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"668546","DOI":"10.3389\/fped.2021.668546","article-title":"Update on the Molecular Genetics of Timothy Syndrome","volume":"9","author":"Bauer","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10545-013-9626-y","article-title":"Niemann-Pick type C Suspicion Index tool: Analyses by age and association of manifestations","volume":"37","author":"Wraith","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1750-1172-5-16","article-title":"Niemann-Pick disease type C","volume":"5","author":"Vanier","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1750-1172-8-12","article-title":"Disease and patient characteristics in NP-C patients: Findings from an international disease registry","volume":"8","author":"Patterson","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13023-015-0240-y","article-title":"Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C","volume":"10","author":"Fecarotta","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/0002-9343(77)90426-0","article-title":"Adult Niemann-Pick disease. Its relationship to the syndrome of the sea-blue histiocyte","volume":"62","author":"Long","year":"1977","journal-title":"Am. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s12288-015-0582-6","article-title":"Secondary Sea-Blue Histiocytosis in a Patient with Transfusion Dependent HbE-Beta Thalassaemia and Osteosarcoma","volume":"32","author":"Bakheet","year":"2016","journal-title":"Indian J. Hematol. Blood Transfus."},{"key":"ref_27","first-page":"e10396","article-title":"Sea Blue Histiocytosis Concordant With Immune Thrombocytopenic Purpura","volume":"12","author":"Bhardwaj","year":"2020","journal-title":"Cureus"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1007\/s13311-013-0217-2","article-title":"Treatment of Niemann-Pick Type C Disease by Histone Deacetylase Inhibitors","volume":"10","author":"Helquist","year":"2013","journal-title":"Neurotherapeutics"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Reddy, J.V., Ganley, I.G., and Pfeffer, S.R. (2006). Clues to neuro-degeneration in Niemann-Pick type C disease from global gene expression profiling. PLoS ONE, 1.","DOI":"10.1371\/journal.pone.0000019"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3389\/fneur.2017.00108","article-title":"Adult-onset Niemann-Pick disease type C: Rapid treatment initiation advised but early diagnosis remains difficult","volume":"8","author":"Piroth","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1186\/s13063-023-07399-6","article-title":"N-acetyl-L-leucine for Niemann-Pick type C: A multinational double-blind randomized placebo-controlled crossover study","volume":"24","author":"Fields","year":"2023","journal-title":"Trials"}],"container-title":["Neurology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2035-8377\/16\/3\/42\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:41:32Z","timestamp":1760107292000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2035-8377\/16\/3\/42"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,13]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["neurolint16030042"],"URL":"https:\/\/doi.org\/10.3390\/neurolint16030042","relation":{},"ISSN":["2035-8377"],"issn-type":[{"value":"2035-8377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,13]]}}}