{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:50:12Z","timestamp":1791481812559,"version":"4.3.4"},"reference-count":10,"publisher":"Walter de Gruyter GmbH","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2026-0131_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Niemann-Pick disease type C (NPC) is a lysosomal lipid trafficking disorder characterized by impaired intracellular cholesterol transport, resulting in progressive neurovisceral involvement. While neurological progression has been extensively described, metabolic biomarkers and lipid abnormalities may provide earlier diagnostic clues, particularly in high-consanguinity populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2026-0131_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively evaluated 14 genetically confirmed NPC patients followed at a tertiary pediatric metabolic center between 2018 and 2025. Clinical presentation, biochemical parameters including HDL cholesterol and lysosphingolipids (LysoSM, LysoSM-509), neuroimaging findings, and molecular genetic results were systematically reviewed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2026-0131_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The cohort (eight males, six females; age range: 9\u00a0days\u201324 years) demonstrated marked phenotypic heterogeneity, including neonatal cholestasis (29\u202f%), pulmonary-dominant disease (29\u202f%), juvenile neurodegeneration (64\u202f%), psychiatric-onset presentation (14\u202f%), and inflammatory bowel disease\u2013like colitis. Low HDL cholesterol was observed in 86\u202f% of patients. LysoSM-509 was elevated in all cases, irrespective of phenotype, supporting its diagnostic robustness. Eleven patients carried\n                      <jats:italic>NPC1<\/jats:italic>\n                      variants and three carried\n                      <jats:italic>NPC2<\/jats:italic>\n                      variants, including several novel truncating pathogenic variants. Marked intrafamilial variability was observed among siblings with identical genotypes. Miglustat treatment appeared to be associated with clinical stabilization in some patients, particularly when initiated at earlier stages of neurological involvement; however, given the limited sample size, no definitive conclusions can be\u00a0drawn.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2026-0131_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NPC should be considered across a broad clinical spectrum, ranging from prenatal presentations such as non-immune hydrops fetalis to adult-onset psychiatric manifestations, as well as neurological involvement at all ages. It should also be suspected in patients presenting with cholestasis, hepatosplenomegaly, developmental delay, interstitial lung disease, or treatment-refractory IBD-like colitis. LysoSM-509 is a highly sensitive biomarker across phenotypes. High consanguinity facilitates early cascade screening but also reveals substantial genotype\u2013phenotype variability. Early biomarker-driven testing remains critical for timely diagnosis and management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2026-0131","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T08:09:05Z","timestamp":1782115745000},"page":"902-909","source":"Crossref","is-referenced-by-count":0,"title":["Diverse clinical spectrum of Niemann-Pick C: insights from a single center"],"prefix":"10.1515","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-5756","authenticated-orcid":false,"given":"Hacer","family":"Basan","sequence":"first","affiliation":[{"name":"Department of Pediatric Metabolic Diseases , Ankara City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6197-0647","authenticated-orcid":false,"given":"Berrak Bilginer","family":"G\u00fcrb\u00fcz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolic Diseases , Ankara City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aynur","family":"K\u00fc\u00e7\u00fckcongar Yava\u015f","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolic Diseases , Ankara City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"G\u00fcnd\u00fcz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolic Diseases , Ankara City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0653-6546","authenticated-orcid":false,"given":"Serpil","family":"Din\u00e7er","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolic Diseases , Ankara City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fenur","family":"Engin Erdal","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolic Diseases , Ankara City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didem","family":"Ardi\u00e7li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology , Ankara City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fczin","family":"Cinel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology , Ankara City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9882-2883","authenticated-orcid":false,"given":"R\u0131dvan","family":"Murat \u00d6ktem","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Metabolic Diseases , Gazi University Faculty of Medicine , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c7i\u011fdem","family":"Seher Kasapkara","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolic Diseases , Ankara City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"2026100816572542514_j_jpem-2026-0131_ref_001","unstructured":"Bremova-Ertl, T, Patterson, M. 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Brain Dev 2023;45:517\u201322. https:\/\/doi.org\/10.1016\/j.braindev.2023.06.006. Submitted for publication.","DOI":"10.1016\/j.braindev.2023.06.006"},{"key":"2026100816572542514_j_jpem-2026-0131_ref_004","doi-asserted-by":"crossref","unstructured":"Mengel, E, Da Riol, RM, Del Toro, M, Deodato, F, Gautschi, M, Grunewald, S, et al.. Long-term efficacy and safety of arimoclomol in Niemann-Pick disease type C: Final results of the phase 2\/3 NPC-002 48-month open-label extension trial. Mol Genet Metabol 2025;145. https:\/\/doi.org\/10.1016\/j.ymgme.2025.109189. Submitted for publication.","DOI":"10.1016\/j.ymgme.2025.109189"},{"key":"2026100816572542514_j_jpem-2026-0131_ref_005","doi-asserted-by":"crossref","unstructured":"Tuna \u00c7ak, H, Halilo\u011flu, G, D\u00fczg\u00fcn, G, Y\u00fcce, A, Top\u00e7u, M. Successful treatment of cataplexy in early-infantile NPC using tricyclic antidepressants. Eur J Paediatr Neurol 2014;18:811\u201315. https:\/\/doi.org\/10.1016\/j.ejpn.2014.07.009.","DOI":"10.1016\/j.ejpn.2014.07.009"},{"key":"2026100816572542514_j_jpem-2026-0131_ref_006","doi-asserted-by":"crossref","unstructured":"Top\u00e7u, M, Aktas, D, \u00d6ztoprak, M, \u00d6nenli Mungan, N, Yuce, A, Alikasifo\u011flu, M. Prospective Turkish cohort study to investigate the frequency of Niemann-Pick disease type C mutations in consanguineous families with at least one homozygous family member. Mol Diagn Ther 2017;21:643\u201351. https:\/\/doi.org\/10.1007\/s40291-017-0293-9.","DOI":"10.1007\/s40291-017-0293-9"},{"key":"2026100816572542514_j_jpem-2026-0131_ref_007","doi-asserted-by":"crossref","unstructured":"Dike, CR, Bernat, J, Bishop, W, DeGeeter, C. Niemann-Pick disease type C presenting as very early onset inflammatory bowel disease. BMJ Case Rep CP 2019;12:e229780. https:\/\/doi.org\/10.1136\/bcr-2019-229780.","DOI":"10.1136\/bcr-2019-229780"},{"key":"2026100816572542514_j_jpem-2026-0131_ref_008","doi-asserted-by":"crossref","unstructured":"Welford, RW, Garzotti, M, Marques Louren\u00e7o, C, Mengel, E, Marquardt, T, Reunert, J, et al.. Plasma lysosphingomyelin demonstrates great potential as a diagnostic biomarker for Niemann-Pick disease type C in a retrospective study. PLoS One 2014;9:e114669. https:\/\/doi.org\/10.1371\/journal.pone.0114669.","DOI":"10.1371\/journal.pone.0114669"},{"key":"2026100816572542514_j_jpem-2026-0131_ref_009","doi-asserted-by":"crossref","unstructured":"Kara, C, K\u00f6se, E, Emino\u011flu, FT. Clinical manifestations and molecular genetics of seven patients with Niemann-Pick type C: a case series with a novel variant. J\u00a0Pediatr Endocrinol Metab 2025;38:539\u201345. https:\/\/doi.org\/10.1515\/jpem-2024-0530.","DOI":"10.1515\/jpem-2024-0530"},{"key":"2026100816572542514_j_jpem-2026-0131_ref_010","doi-asserted-by":"crossref","unstructured":"Patterson, MC, Ramaswami, U, Brands, M, Foltan, T, Gautschi, M, Gissen, P, et al.. Trial of N-acetyl-L-leucine in Niemann-Pick disease type C. 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