title: A Suspicion Index to aid screening of early-onset Niemann-Pick disease Type C (NP-C).
abstract: Niemann-Pick disease Type C (NP-C) is difficult to diagnose due to heterogeneous and nonspecific clinical presentation. The NP-C Suspicion Index (SI) was developed to identify patients with a high likelihood of NP-C; however, it was less reliable in patients aged <4 years.
  
  
  
  An early-onset NP-C SI was constructed following retrospective chart review of symptom presentation in 200 patients from nine centres comprised of 106 NP-C cases, 31 non-cases and 63 controls. Statistical analyses defined strength of association between symptoms and a diagnosis of NP-C and assigned risk prediction scores to each symptom.
  
  
  
  Visceral symptoms were amongst the strongest predictors. Except for gelastic cataplexy and vertical supranuclear gaze palsy, central nervous system symptoms were not discriminatory in this population. Performance of the early-onset NP-C SI was superior versus the original NP-C SI in patients aged ≤4 years.
  
  
  
  The early-onset NP-C SI can help physicians, especially those with limited knowledge of NP-C, to identify patients aged ≤4 years who warrant further investigation for NP-C.
authors.affiliation: Fundació, Hospital Sant Joan de Déu, Centre for Biomedical Research on Rare Diseases, CIBERER, Instituto de Salud Carlos III, Barcelona, Spain. pineda@hsjdbcn.org.|Hospital Sant Joan de Deu, Passeig de Sant Joan de Deu n°2, Esplugues de Llobregat, Barcelona, 08950, Spain. pineda@hsjdbcn.org.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Pineda
authors.affiliation: Villa Metabolica, Center for Pediatric and Adolescent Medicine, MC University of Mainz, Mainz, Germany.
authors.forename: Eugen
authors.initials: E
authors.lastname: Mengel
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Jahnová
authors.affiliation: Centre de Référence des Maladies Lysosomales (CRML), Neuropédiatrie, CHU Trousseau, APHP, Paris, France.|Committee for the Evaluation of Treatment for Niemann-Pick diseases (CETNP), Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Héron
authors.affiliation: Niemann-Pick UK, Vermont House, Tyne and Wear, Washington, UK.
authors.forename: Jackie
authors.initials: J
authors.lastname: Imrie
authors.affiliation: Medical Genetics Service, Clinics Hospital of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Lourenço
authors.affiliation: Association of Assistance to Deficient Children of Pernambuco, Barão de Lucena Hospital, Recife, PE, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: van der Linden
authors.affiliation: Department of Paediatric Neurology, Paediatric Neurology Research Centre, Shahid Beheshti University of Medical Sciences, Mofid Children Hospital, Tehran, Iran.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Karimzadeh
authors.affiliation: Committee for the Evaluation of Treatment for Niemann-Pick diseases (CETNP), Paris, France.|Centre Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte (MaMEA), Necker-Enfants Malades and IMAGINE Institute, APHP, Paris, France.
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Jesina
authors.affiliation: Syntax for Science, Basel, Switzerland.
authors.forename: Juan V
authors.initials: JV
authors.lastname: Torres
authors.affiliation: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Kolb
mesh_terms: D000367:Age Factors; D016022:Case-Control Studies; D002675:Child, Preschool; D003661:Decision Support Techniques; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D052556:Niemann-Pick Disease, Type C / Q000175:diagnosis*; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity
keywords: Diagnosis; Diagnostics; Early-onset; Infant; NP-C; Niemann-Pick disease Type C; Paediatric; Screening; Suspicion Index