The hidden Niemann-Pick type C patient: clinical niches for a rare inherited metabolic disease

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Background: 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.


  • Christian J. Hendriksz
  • Mathieu Anheim
  • Peter Bauer
  • Olivier Bonnot
  • Anupam Chakrapani
  • Jean Christophe Corvol
  • Anna Degtyareva
  • Carlo Dionisi-Vici
  • Sarah Doss
  • Thomas Duning
  • Paola Giunti
  • Rosa Iodice
  • Tracy Johnston
  • Dierdre Kelly
  • Hans Hermann Klünemann
  • Stefan Lorenzl
  • Alessandro Padovani
  • Miguel Pocovi
  • Matthis Synofzik
  • Alta Terblanche
  • Florian Then Bergh
  • Meral Topçu
  • Christine Tranchant
  • Mark Walterfang
  • Christian Velten
  • Stefan A. Kolb
Externa organisationer
  • Salford Royal NHS FoundationTrust
  • University of Pretoria
  • University of Strasbourg
  • University of Tübingen
  • Centogene AG
  • University of Nantes
  • Pitié Salpetriere University Paris
  • University of Groningen
  • Bambino Gesù Children’s Hospital
  • Charité Universitätsmedizin Berlin
  • Universitätsklinikum Münster
  • University College London
  • University of Naples Federico II
  • Birmingham Women’s Hospital Healthcare NHS Trust
  • Birmingham Children's Hospital
  • University Hospital Regensburg
  • University Hospital Salzburg
  • University of Brescia
  • University of Zaragoza
  • German Center for Neurodegenerative Diseases
  • Leipzig University
  • Hacettepe University
  • Institut de Biologie Moléculaire et Cellulaire Immunopathologie et Chimie Thérapeutique
  • Royal Melbourne Hospital
  • Actelion Pharmaceuticals Ltd.

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi


Sidor (från-till)877-890
Antal sidor14
TidskriftCurrent Medical Research and Opinion
Utgåva nummer5
StatusPublished - 2017 maj 4
Peer review utfördJa
Externt publiceradJa