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

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

Proportions of NP-C EOA cases and EOA controls with low, moderate and high RPS on the original NP-C SI
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5037150&req=5

Fig2: Proportions of NP-C EOA cases and EOA controls with low, moderate and high RPS on the original NP-C SI

Mentions: Findings from the descriptive analysis of the proportions of patients with low (0–39 points), moderate (40–69 points) or high (≥70 points) RPS are summarised in Fig. 2. A notable number of EOA control patients had a moderate [n = 16/86 (19 %)] or high [n = 8/86 (9 %)] RPS. However, the scores of the NP-C EOA cases were significantly higher (p < 0.001, Fisher’s exact test), and most of them had a high RPS [46/47 (98 %)].Fig. 2


Identifying Niemann – Pick type C in early-onset ataxia: two quick clinical screening tools
Proportions of NP-C EOA cases and EOA controls with low, moderate and high RPS on the original NP-C SI
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Proportions of NP-C EOA cases and EOA controls with low, moderate and high RPS on the original NP-C SI
Mentions: Findings from the descriptive analysis of the proportions of patients with low (0–39 points), moderate (40–69 points) or high (≥70 points) RPS are summarised in Fig. 2. A notable number of EOA control patients had a moderate [n = 16/86 (19 %)] or high [n = 8/86 (9 %)] RPS. However, the scores of the NP-C EOA cases were significantly higher (p < 0.001, Fisher’s exact test), and most of them had a high RPS [46/47 (98 %)].Fig. 2

View Article: PubMed Central - PubMed

ABSTRACT

Niemann&ndash;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&ndash;90&nbsp;% 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 &lsquo;2/3 SI&rsquo; tool for rapid appraisal of suspected NP-C in unexplained EOA. This was a retrospective observational study comparing &lsquo;NP-C EOA&rsquo; 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&ndash;69 points) and high (&ge;70 points) RPS were common based on original SI assessments in non-NP-C EOA controls [16 (19&nbsp;%) and 8 (9&nbsp;%), respectively], but scores &ge;70 points were far more frequent [46 (98&nbsp;%)] among NP-C EOA cases. RPS cut-off values provided 98&nbsp;% sensitivity and 91&nbsp;% specificity for NP-C at 70-point cut-off, and ROC analysis revealed an AUC of 0.982. Using the 2/3 SI, 90&nbsp;% 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