A Suspicion Index to aid screening of early-onset Niemann-Pick disease Type C (NP-C)

BMC Pediatr. 2016 Jul 22;16:107. doi: 10.1186/s12887-016-0641-7.


Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Diagnosis; Diagnostics; Early-onset; Infant; NP-C; Niemann-Pick disease Type C; Paediatric; Screening; Suspicion Index.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Case-Control Studies
  • Child, Preschool
  • Decision Support Techniques*
  • Female
  • Health Status Indicators*
  • Humans
  • Infant
  • Infant, Newborn
  • Logistic Models
  • Male
  • Niemann-Pick Disease, Type C / diagnosis*
  • Retrospective Studies
  • Risk Assessment
  • Sensitivity and Specificity