Identifying Niemann–Pick type C in early-onset ataxia: two quick clinical screening tools

Autor: Peter Bauer, Jennifer Just, Ludger Schöls, Stefan A. Kolb, Juan V. Torres Martin, Zofia Fleszar, Matthis Synofzik
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Adult
Male
medicine.medical_specialty
Adolescent
diagnosis [Niemann-Pick Disease
Type C]
Clinical Neurology
Suspicion index
030105 genetics & heredity
Gene mutation
Gastroenterology
Statistics
Nonparametric
03 medical and health sciences
Young Adult
0302 clinical medicine
Internal medicine
Diagnosis
medicine
Humans
Mass Screening
methods [Mass Screening]
ddc:610
Child
complications [Niemann-Pick Disease
Type C]
Retrospective Studies
Niemann–Pick disease
type C
Original Communication
Clinical screening
business.industry
Niemann–Pick disease type C
Retrospective cohort study
Niemann-Pick Disease
Type C
Middle Aged
medicine.disease
Surgery
Early onset ataxia
Neurology
ROC Curve
Child
Preschool
Ataxia
Female
Neurology (clinical)
business
030217 neurology & neurosurgery
complications [Ataxia]
Zdroj: Journal of Neurology
Journal of neurology 263(10), 1911-1918 (2016). doi:10.1007/s00415-016-8178-0
ISSN: 1432-1459
0340-5354
DOI: 10.1007/s00415-016-8178-0
Popis: Niemann–Pick disease type C (NP-C) is a rare multisystemic lysosomal disorder which, albeit treatable, is still starkly underdiagnosed. As NP-C features early onset ataxia (EOA) in 85–90 % of cases, EOA presents a promising target group for undiagnosed NP-C patients. Here, we assessed the ability of the previously established NP-C suspicion index (SI) and a novel abbreviated ‘2/3 SI’ tool for rapid appraisal of suspected NP-C in unexplained EOA. This was a retrospective observational study comparing ‘NP-C EOA’ cases (EOA patients with confirmed NP-C) with non-NP-C EOA controls (EOA patients negative for NP-C gene mutations). NP-C risk prediction scores (RPS) from both the original and 2/3 SIs were calculated and their discriminatory performance evaluated. Among 133 patients (47 NP-C EOA cases; 86 non-NP-C EOA controls), moderate (40–69 points) and high (≥70 points) RPS were common based on original SI assessments in non-NP-C EOA controls [16 (19 %) and 8 (9 %), respectively], but scores ≥70 points were far more frequent [46 (98 %)] among NP-C EOA cases. RPS cut-off values provided 98 % sensitivity and 91 % specificity for NP-C at 70-point cut-off, and ROC analysis revealed an AUC of 0.982. Using the 2/3 SI, 90 % of NP-C EOA cases had scores of 2 or 3, and RPS analysis showed an AUC of 0.961. In conclusion, the NP-C SI and the new, quick-to-apply 2/3 SI distinguished well between NP-C and non-NP-C patients, even in EOA populations with high background levels of broadly NPC-compatible multisystemic disease features. While the original SI showed the greatest sensitivity, both tools reliably aided identification of patients with unexplained EOA who warranted further investigation for NP-C. Electronic supplementary material The online version of this article (doi:10.1007/s00415-016-8178-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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