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

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ABSTRACT

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.

No MeSH data available.


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Distribution of 2/3 SI scores among NP-C EOA cases and EOA controls
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Fig5: Distribution of 2/3 SI scores among NP-C EOA cases and EOA controls

Mentions: We observed a clear difference in the distribution of 2/3 SI scores between NP-C EOA cases and EOA controls (Fig. 5). In total, 90 % of NP-C EOA cases had 2/3 SI scores of 2 or 3. In contrast, 90 % of EOA controls had scores of 0 or 1 on this tool. Based on ROC analyses, the 2/3 SI tool was effective at discriminating NP-C EOA cases from EOA controls, providing an AUC of 0.961 in NP-C EOA cases versus EOA controls, which is comparable with the excellent value achieved with the original SI tool in this ataxia cohort.Fig. 5


Identifying Niemann – Pick type C in early-onset ataxia: two quick clinical screening tools
Distribution of 2/3 SI scores among NP-C EOA cases and EOA controls
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037150&req=5

Fig5: Distribution of 2/3 SI scores among NP-C EOA cases and EOA controls
Mentions: We observed a clear difference in the distribution of 2/3 SI scores between NP-C EOA cases and EOA controls (Fig. 5). In total, 90 % of NP-C EOA cases had 2/3 SI scores of 2 or 3. In contrast, 90 % of EOA controls had scores of 0 or 1 on this tool. Based on ROC analyses, the 2/3 SI tool was effective at discriminating NP-C EOA cases from EOA controls, providing an AUC of 0.961 in NP-C EOA cases versus EOA controls, which is comparable with the excellent value achieved with the original SI tool in this ataxia cohort.Fig. 5

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus