Niemann-Pick type C Suspicion Index tool: analyses by age and association of manifestations

J Inherit Metab Dis. 2014 Jan;37(1):93-101. doi: 10.1007/s10545-013-9626-y. Epub 2013 Jun 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Ataxia / complications
  • Child
  • Child, Preschool
  • Cognition Disorders / complications
  • Data Collection
  • Decision Support Techniques
  • Female
  • Humans
  • Infant
  • Logistic Models
  • Male
  • Mass Screening / methods
  • Niemann-Pick Disease, Type C / diagnosis*
  • Phenotype
  • Psychotic Disorders / complications
  • ROC Curve
  • Retrospective Studies
  • Risk
  • Splenomegaly / complications