{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:20:13Z","timestamp":1760235613977,"version":"build-2065373602"},"reference-count":22,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T00:00:00Z","timestamp":1631836800000},"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>Background: To report on clinical presentation and outcomes of children who underwent liver transplantation (LTx) and were subsequently diagnosed to have Niemann-Pick type C (NPC). Methods: Retrospective, descriptive, multi-centre review of children diagnosed with NPC who underwent LTx (2003\u20132018). Diagnosis was made by filipin skin test or genetic testing. Results: Nine children were identified (six centres). Neonatal acute liver failure was the most common indication for LTx (seven children). Median age at first presentation: 7 days (range: 0\u201337). The most prevalent presenting symptoms: jaundice (8\/9), hepatosplenomegaly (8\/9) and ascites (6\/9). 8\/9 children had a LTx before the diagnosis of NPC. Genetic testing revealed mutations in NPC1 correlating with a severe biochemical phenotype in 5 patients. All 9 children survived beyond early infancy. Seven children are still alive (median follow-up time of 9 (range: 6\u201313) years). Neurological symptoms developed in 4\/7 (57%) patients at median 9 (range: 5\u201313) years following LTx. Conclusion: Early diagnosis of NPC continues to be a challenge and a definitive diagnosis is often made only after LTx. Neurological disease is not prevented in the majority of patients. Genotype does not appear to predict neurological outcome after LTx. LTx still remains controversial in NPC.<\/jats:p>","DOI":"10.3390\/children8090819","type":"journal-article","created":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T21:23:29Z","timestamp":1631913809000},"page":"819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Case Series on Genotype and Outcome of Liver Transplantation in Children with Niemann-Pick Disease Type C"],"prefix":"10.3390","volume":"8","author":[{"given":"Line","family":"Modin","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hans Christian Andersen Children\u2019s Hospital, DK-5000 Odense, Denmark"},{"name":"Liver Department, Birmingham Children\u2019s Hospital, Steelhouse Ln, Birmingham B4 6NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicky","family":"Ng","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9712-6122","authenticated-orcid":false,"given":"Paul","family":"Gissen","sequence":"additional","affiliation":[{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Raiman","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva Doreen","family":"Pfister","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5884-0852","authenticated-orcid":false,"given":"Anibh","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"Santer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, \"KiNDER-UKE\", University Medical Center Eppendorf, Martini Str. 52 (O45), 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Faghfoury","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saikat","family":"Santra","sequence":"additional","affiliation":[{"name":"Liver Department, Birmingham Children\u2019s Hospital, Steelhouse Ln, Birmingham B4 6NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Baumann","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology and Hepatology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.jpeds.2011.04.016","article-title":"Characterization and Outcomes of Young Infants with Acute Liver Failure","volume":"159","author":"Sundaram","year":"2011","journal-title":"J. Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"501","DOI":"10.5223\/pghn.2020.23.6.501","article-title":"Differential Diagnosis of Acute Liver Failure in Children: A Systematic Review","volume":"23","author":"Berardi","year":"2020","journal-title":"Pediatr. Gastroenterol. Hepatol. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/MPG.0000000000003103","article-title":"Applying an Age-specific Definition to Better Characterize Etiologies and Outcomes in Neonatal Acute Liver Failure","volume":"73","author":"Borovsky","year":"2021","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10545-006-0384-7","article-title":"The natural history of Niemann-Pick disease type C in the UK","volume":"30","author":"Imrie","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Imrie, J., Heptinstall, L., Knight, S., and Strong, K. (2015). Observational cohort study of the natural history of Niemann-Pick disease type C in the UK: A 5-year update from the UK clinical database. BMC Neurol., 15.","DOI":"10.1186\/s12883-015-0511-1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1016\/B978-0-444-59565-2.00041-1","article-title":"Niemann-Pick diseases","volume":"113","author":"Vanier","year":"2013","journal-title":"Handb. Clin. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1146\/annurev-med-122313-085916","article-title":"Lysosomal storage diseases: From pathophysiology to therapy","volume":"66","author":"Parenti","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1212\/WNL.39.8.1040","article-title":"Clinical spectrum of Niemann-Pick disease type C","volume":"39","author":"Fink","year":"1989","journal-title":"Neurology"},{"key":"ref_9","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\u2013Pick disease type C: An update","volume":"106","author":"Patterson","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.ymgme.2016.06.004","article-title":"Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review","volume":"118","author":"Vanier","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/9781119046936.ch19","article-title":"Metabolic Liver Disease in the Infant and Older Child","volume":"37","author":"Chakrapani","year":"2017","journal-title":"Dis. Liver Biliary Syst. Child."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"e13462","DOI":"10.1111\/petr.13462","article-title":"Pediatric liver transplantation for neonatal-onset Niemann-Pick disease type C: Japanese multicenter experience","volume":"23","author":"Yamada","year":"2019","journal-title":"Pediatr. Transplant."},{"key":"ref_15","first-page":"624","article-title":"Metastatic hepatocellular carcinoma in a patient with niemann-pick disease, type C","volume":"37","author":"Birch","year":"2003","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0022-3476(05)81695-6","article-title":"Niemann-Pick disease type C: Diagnosis and outcome in children, with particular reference to liver disease","volume":"123","author":"Kelly","year":"1993","journal-title":"J. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/0925-4439(91)90069-L","article-title":"Type C Niemann-Pick disease: Spectrum of phenotypic variation in disruption of intracellular LDL-derived cholesterol processing","volume":"1096","author":"Vanier","year":"1991","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1073\/pnas.90.5.2002","article-title":"Linkage of Niemann-Pick disease type C to human chromosome 18","volume":"90","author":"Carstea","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","first-page":"118","article-title":"Genetic heterogeneity in Niemann-Pick C disease: A study using somatic cell hybridization and linkage analysis","volume":"58","author":"Vanier","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1086\/302626","article-title":"Niemann-Pick C1 Disease: The I1061T Substitution Is a Frequent Mutant Allele in Patients of Western European Descent and Correlates with a Classic Juvenile Phenotype","volume":"65","author":"Millat","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1136\/adc.2005.088013","article-title":"The usefulness of bone marrow aspiration in the diagnosis of Niemann-Pick disease type C in infantile liver disease","volume":"91","author":"Rodrigues","year":"2006","journal-title":"Arch. Dis. Child."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s10545-006-0363-3","article-title":"Critical assessment of chitotriosidase analysis in the rational laboratory diagnosis of children with Gaucher disease and Niemann-Pick disease type A\/B and C","volume":"29","author":"Ries","year":"2006","journal-title":"J. Inherit. Metab. Dis."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/8\/9\/819\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:01:21Z","timestamp":1760166081000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/8\/9\/819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,17]]},"references-count":22,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["children8090819"],"URL":"https:\/\/doi.org\/10.3390\/children8090819","relation":{},"ISSN":["2227-9067"],"issn-type":[{"type":"electronic","value":"2227-9067"}],"subject":[],"published":{"date-parts":[[2021,9,17]]}}}