{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T11:17:00Z","timestamp":1760267820156,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Niemann\u2013Pick disease type C (NPC) is an autosomal recessive lipid storage disorder. There are two types, NPC1, which is the predominant form (95%), and the rare NPC2, which represents less than 5% of the reported cases. Niemann\u2013Pick disease type C2 usually presents with respiratory symptoms, cholestasis, neurological impairment, and hepatosplenomegaly. Case report: Here, we report a 3-year-old boy who presented to our hospital with exacerbation of chronic lung disease requiring invasive ventilatory support. He was previously diagnosed with interstitial lung disease. His parents used to instill olive oil in his nose (a few drops in each nostril daily for several months) to treat frequent nasal bleeding. A detailed history revealed prolonged neonatal jaundice for four months, with hepatosplenomegaly. In his second year, generalized hypotonia and delayed psychomotor development were observed. Upon presentation to our institute, chest CT showed evidence of intraparenchymal fat; therefore, lipoid pneumonia and lipid storage disease were suspected. The bronchoalveolar lavage results suggested pulmonary alveolar proteinosis (PAP). Whole-exome sequencing (WES) revealed a class one homozygous pathogenic variant in the NPC2 gene. Our patient faced a range of difficulties, including prolonged mechanical ventilation and diagnostic and therapeutic challenges. Conclusion: Niemann\u2013Pick disease type C2 is a progressive and lethal condition that requires a high index of suspicion to pinpoint the diagnosis. Gene study remains the method of choice to confirm the diagnosis. There are limited choices of therapeutic interventions; therefore, genetic counseling and the prevention of recurrence should be the ultimate goal for affected families.<\/jats:p>","DOI":"10.3390\/children9121811","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T05:35:08Z","timestamp":1669268108000},"page":"1811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Niemann\u2013Pick Disease Type C2 with Severe Pulmonary Involvement and Limited Therapeutic Options: A Case Report"],"prefix":"10.3390","volume":"9","author":[{"given":"Abdullah","family":"Al-Shamrani","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Prince Sultan Military Medical City (PSMMC), Riyadh 11159, Saudi Arabia"},{"name":"Al Faisal University, Riyadh 11159, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalid","family":"Al-Shamrani","sequence":"additional","affiliation":[{"name":"College of Medicine, Al Marifah University, Riyadh 11159, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed Bin","family":"Mahfoudh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Hospital, Riyadh 11159, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed Sarar","family":"Mohamed","sequence":"additional","affiliation":[{"name":"College of Medicine, The National University, Khartoum 11115, Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7393-5064","authenticated-orcid":false,"given":"Sarar","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Prince Sultan Military Medical City (PSMMC), Riyadh 11159, Saudi Arabia"},{"name":"Al Faisal University, Riyadh 11159, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"ref_1","first-page":"37","article-title":"Pulmonary alveolar proteinosis and Niemann Pick disease type B: An unexpected combination Georgios","volume":"19","author":"Sideris","year":"2016","journal-title":"Respir. Med. Case Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.beem.2014.10.002","article-title":"Types A and B Niemann-Pick disease","volume":"29","author":"Schuchman","year":"2015","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_3","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_4","first-page":"S39","article-title":"Phenotypic diversity of Niemann-Pick disease type C in Pakistani children","volume":"129","author":"Cheema","year":"2020","journal-title":"Mol. Genet. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/j.1399-0004.2007.00782.x","article-title":"Niemann-Pick C disease: Functional characterization of three NPC2 mutations and clinical and molecular update on patients with NPC2","volume":"71","author":"Verot","year":"2007","journal-title":"Clin. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ymgme.2013.05.019","article-title":"Identification of mutation in NPC2 by exome sequencing results in diagnosis of Niemann-Pick disease type C","volume":"110","author":"Alavi","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/j.1365-2559.2006.02355.x","article-title":"Pulmonary involvement by Niemann\u2013Pick disease. A report of six cases","volume":"48","author":"Nicholson","year":"2006","journal-title":"Histopathology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1053\/rmed.2000.0942","article-title":"Pulmonary involvement in Niemann\u2013Pick disease: Case report and literature review","volume":"94","author":"Minai","year":"2000","journal-title":"Respir. Med."},{"key":"ref_9","unstructured":"Adam, M.P., Everman, D.B., Mirzaa, G.M., Pagon, R.A., and Wallace, S.E. (2022, November 22). Niemann-Pick Disease Type C, GeneReviews\u00ae, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13023-018-0785-7","article-title":"Gene Reviews Consensus clinical management guidelines for Niemann-Pick disease type C","volume":"13","author":"Geberhiwot","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1515\/jpem-2014-0358","article-title":"A rare cause of fatal pulmonary alveolar proteinosis: Niemann-Pick disease type C2 and a novel mutation","volume":"28","author":"Yaman","year":"2015","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_12","first-page":"CS71","article-title":"Niemann-Pick disease type C2 presenting as fatal pulmonary alveolar lipoproteinosis: Morphological findings in lung and nervous tissue","volume":"14","author":"Bjurulf","year":"2008","journal-title":"Med. Sci. Monit."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1586\/17476348.2015.1035259","article-title":"Pulmonary alveolar proteinosis: Time to shift","volume":"9","author":"Papiris","year":"2015","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_14","first-page":"1","article-title":"Lipoid pneumonia treated with modified therapeutic lung lavage","volume":"21","author":"AlFadl","year":"2020","journal-title":"Sudan Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103","DOI":"10.2214\/AJR.09.3040","article-title":"Lipoid Pneumonia: Spectrum of Clinical and Radiologic Manifestations","volume":"194","author":"Betancourt","year":"2010","journal-title":"Am. J. Roentgenol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s00408-016-9893-0","article-title":"Pulmonary Involvement in Niemann\u2013Pick Disease: A State-of-the-Art Review","volume":"194","author":"Freitas","year":"2016","journal-title":"Lung"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1007\/s004280100407","article-title":"Pulmonary storage with emphysema as a sign of Niemann\u2013Pick type C2 disease (second complementation group). Report of a case","volume":"439","author":"Elleder","year":"2001","journal-title":"Virchows Arch."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s13023-018-0844-0","article-title":"Miglustat in Niemann-Pick disease type C patients: A review","volume":"13","author":"Pineda","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ymgme.2008.10.002","article-title":"24-month treatment with miglustat of three patients with Niemann-Pick disease type C: Follow up using brain spectroscopy","volume":"96","author":"Galanaud","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/sj.bmt.1701826","article-title":"Niemann\u2013Pick disease type C (a cellular cholesterol lipidosis) treated by bone marrow transplantation","volume":"24","author":"Hsu","year":"1999","journal-title":"Bone Marrow Transplant."},{"key":"ref_21","first-page":"c5428381","article-title":"Double-Lung Transplantation in a Patient with Pulmonary Type B Niemann-Pick Disease: A Valid Treatment Option","volume":"2022","author":"Mora","year":"2022","journal-title":"Case Rep. Transplant."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.braindev.2019.01.004","article-title":"A case of Niemann-Pick disease type C with neonatal liver failure initially diagnosed as neonatal hemochromatosis","volume":"41","author":"Kumagai","year":"2019","journal-title":"Brain Dev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/ajt.16819","article-title":"Normal long-term neurologic and graft outcome after liver transplantation in an infant with Neimann-Pick type C disease","volume":"22","author":"Lemoine","year":"2021","journal-title":"Am. J. Transplant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/humu.20173","article-title":"Niemann-Pick type C disease: Subcellular location and functional characterization of NPC2 proteins with naturally occurring missense mutations","volume":"26","author":"Chikh","year":"2005","journal-title":"Hum. Mutat."},{"key":"ref_25","unstructured":"(2022, November 22). Mutation Taster Documentaion. Available online: https:\/\/www.mutationtaster.org\/info\/documentation.html."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/12\/1811\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:25:57Z","timestamp":1760145957000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/12\/1811"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":25,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["children9121811"],"URL":"https:\/\/doi.org\/10.3390\/children9121811","relation":{},"ISSN":["2227-9067"],"issn-type":[{"type":"electronic","value":"2227-9067"}],"subject":[],"published":{"date-parts":[[2022,11,24]]}}}