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

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Journal of Neurology

, Volume 263, Issue 10, pp 1911–1918

First Online: 17 June 2016Received: 23 February 2016Revised: 26 April 2016Accepted: 17 May 2016


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.

KeywordsNiemann–Pick disease type C Early onset ataxia Suspicion index Diagnosis Electronic supplementary materialThe online version of this article doi:10.1007-s00415-016-8178-0 contains supplementary material, which is available to authorized users.

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Author: Matthis Synofzik - Zofia Fleszar - Ludger Schöls - Jennifer Just - Peter Bauer - Juan V. Torres Martin - Stefan Kolb


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