title: Niemann-Pick type C Suspicion Index tool: analyses by age and association of manifestations.
abstract: OBJECTIVE
  The Suspicion Index (SI) screening tool was developed to identify patients suspected of having Niemann-Pick disease type C (NP-C). The SI provides a risk prediction score (RPS) based on NP-C manifestations within and across domains (visceral, neurological, and psychiatric). The aim of these subanalyses was to further examine the discriminatory power of the SI by age and manifestation-associations by NP-C suspicion-level and leading manifestations.
  
  
  METHODS
  The original retrospectively collected data were split into three patient age groups, where NP-C-positive cases were >16 years (n = 30), 4-16 years (n = 18), and <4 years (n = 23), and patients' RPS were analyzed by logistic regression. Co-occurrence of manifestations within groups of suspicion level (low, medium, high) and leading manifestations (presence/absence of ataxia, cognitive decline, psychosis, and splenomegaly) were analyzed descriptively.
  
  
  RESULTS
  NP-C-positive cases versus controls showed strong discriminatory power of RPS. Area under the receiver operating characteristic curve was 0.964 (>16 years) and 0.981 (4-16 years) but weaker 0.562 for infants (<4 years). Patients with RPS <70 were characterized by a lack of psychiatric manifestations and low levels of neurological involvement, suggestive of a preneurological phase of the disease. In patients >4 years, prominent leading manifestation-associations were ataxia with dystonia, dysarthria/dysphagia, and cognitive decline. Psychosis was associated with dysarthria/dysphagia but also with cognitive decline and treatment-resistant psychiatric symptoms.
  
  
  CONCLUSIONS
  The SI tool maintains strong discriminatory power in patients >4 years but is not as useful for infants <4 years. The SI is also informative regarding the association and co-occurrence of manifestations in patients with NP-C.
authors.affiliation: Genetic Medicine, St. Mary's Hospital, Oxford Road, Manchester, M13 9WL, UK.
authors.forename: James E
authors.initials: JE
authors.lastname: Wraith
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sedel
authors.forename: Mercèdes
authors.initials: M
authors.lastname: Pineda
authors.forename: Frits A
authors.initials: FA
authors.lastname: Wijburg
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Hendriksz
authors.forename: Michael
authors.initials: M
authors.lastname: Fahey
authors.forename: Mark
authors.initials: M
authors.lastname: Walterfang
authors.forename: Marc C
authors.initials: MC
authors.lastname: Patterson
authors.forename: Harbajan
authors.initials: H
authors.lastname: Chadha-Boreham
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Kolb
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001259:Ataxia / Q000150:complications; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000150:complications; D003625:Data Collection; D003661:Decision Support Techniques; D005260:Female; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D008403:Mass Screening / Q000379:methods; D052556:Niemann-Pick Disease, Type C / Q000175:diagnosis*; D010641:Phenotype; D011618:Psychotic Disorders / Q000150:complications; D012372:ROC Curve; D012189:Retrospective Studies; D012306:Risk; D013163:Splenomegaly / Q000150:complications