Hendriksz, Christian J.Anheim, MathieuBauer, PeterBonnot, OlivierChakrapani, AnupamCorvol, Jean-ChristopheDe Koning, Tomas J.Degtyareva, AnnaDionisi-Vici, CarloDoss, SarahDuning, ThomasGiunti, PaolaIodice, RosaJohnston, TracyKelly, DierdreKlünemann, Hans-HermannLorenzl, StefanPadovani, AlessandroPocovi, MiguelSynofzik, MatthisTerblanche, Alta J.Then Bergh, FlorianTopçu, MeralTranchant, ChristineWalterfang, MarkVelten, Christian E.Kolb, Stefan A.2018-03-012017-03Christian J. Hendriksz, Mathieu Anheim, Peter Bauer, Olivier Bonnot, Anupam Chakrapani, Jean-Christophe Corvol, Tom J. de Koning, Anna Degtyareva, Carlo Dionisi-Vici, Sarah Doss, Thomas Duning, Paola Giunti, Rosa Iodice, Tracy Johnston, Dierdre Kelly, Hans- Hermann Kl ünemann, Stefan Lorenzl, Alessandro Padovani, Miguel Pocovi, Matthis Synofzik, Alta Terblanche, Florian Then Bergh, Meral Top çu, Christine Tranchant, Mark Walterfang, Christian Velten & Stefan A. Kolb (2017) The hidden Niemann-Pick type C patient: clinical niches for a rare inherited metabolic disease, Current Medical Research and Opinion, 33:5, 877-890, DOI: 10.1080/03007995.2017.1294054.0300-7995 (print)1473-4877 (online)10.1080/03007995.2017.1294054http://hdl.handle.net/2263/64137BACKGROUND : Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups (“clinical niches”) have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. METHODS : Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. FINDINGS : Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. CONCLUSIONS : Several clinical niches have been identified that harbor patients at increased risk of NP-C.en© 2017 Informa UK Limited, trading as Taylor & Francis Group. This is an electronic version of an article published in Current Medical Research and Opinion, vol. 33, no. 5, pp. 877-890, 2017. doi : 10.1080/03007995.2017.1294054. Current Medical Research and Opinion is available online at :http://www.tandfonline.com/loi/icmo20.Niemann-Pick disease type C (NP-C)DiagnosisScreeningClinical nicheDifferential diagnosisEpidemiologyInborn errors of metabolism (IEM)Early-onset ataxia (EOA)SchizophreniaMultiple sclerosis (MS)Genotype-phenotype correlationsHexanucleotide repeat expansionFrontotemporal lobar degeneration-tau (FTLD-tau)Amyotrophic lateral sclerosisProgressive supranuclear gaze palsy (PSP)Postprint Article