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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.


Related in: MedlinePlus

Symptom frequency in NP-C EOA cases versus EOA controls
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Fig1: Symptom frequency in NP-C EOA cases versus EOA controls

Mentions: The frequencies of NP-C signs and symptoms included in the original NP-C SI tool [15] in both EOA groups are summarised in Fig. 1. Among neurological manifestations, VSGP, cognitive decline/dementia and dysarthria/dysphagia were all recorded in association with ataxia in >80 % of NP-C EOA cases. Among EOA controls, the most common neurological manifestations (observed in >50 % patients) were dysarthria/dysphagia (in 87 % patients) and spasticity (in 58 %).Fig. 1


Identifying Niemann – Pick type C in early-onset ataxia: two quick clinical screening tools
Symptom frequency in NP-C EOA cases versus EOA controls
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Symptom frequency in NP-C EOA cases versus EOA controls
Mentions: The frequencies of NP-C signs and symptoms included in the original NP-C SI tool [15] in both EOA groups are summarised in Fig. 1. Among neurological manifestations, VSGP, cognitive decline/dementia and dysarthria/dysphagia were all recorded in association with ataxia in >80 % of NP-C EOA cases. Among EOA controls, the most common neurological manifestations (observed in >50 % patients) were dysarthria/dysphagia (in 87 % patients) and spasticity (in 58 %).Fig. 1

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