Niemann-Pick disease type C clinical database: cognitive and coordination deficits are early disease indicators

Orphanet Journal of Rare Diseases

Heiko Runz²  Christine Fischer⁴  Eugen Mengel³  Daniel S Ory¹  Sigrid Keller³  Xuntian Jiang¹  Yasmina Amraoui³  Susanne Theiss⁴  Miriam Stampfer⁴ 

[1] Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO, USA;Molecular Medicine Partnership Unit (MMPU), University of Heidelberg/EMBL, Heidelberg, Germany;Center for Pediatric and Adolescent Medicine, University of Mainz, Mainz, Germany;Institute of Human Genetics, University of Heidelberg, INF 366, Heidelberg 69120, Germany

关键词: Oxysterols;    Neurodegenerative disease;    Genotype-phenotype;    Clinical repository;    Cholesterol;   

Others  :  864097
DOI  :  10.1186/1750-1172-8-35

 received in 2012-10-13, accepted in 2013-02-18,  发布年份 2013

【 摘 要 】

Background

The neurodegenerative lysosomal storage disorder Niemann-Pick disease type C (NP-C) is characterized by a broad clinical variability involving neurological, psychiatric and systemic signs. Diverse patterns of disease manifestation and progression considerably delay its diagnosis. Here we introduce the NP-C clinical database (NPC-cdb) to systematically obtain, store and analyze diagnostic and clinical findings in patients with NP-C. We apply NPC-cdb to study NP-C temporal expression in a large German-Swiss patient cohort.

Methods

Current and past medical history was systematically acquired from 42 patients using tailored questionnaires. Manifestation of 72 distinct neuropsychiatric signs was modeled over the course of disease. The sequence of disease progression was re-constructed by a novel clinical outcome scale (NPC-cdb score).

Results

The efficiency of current clinical diagnostic standards negatively correlates with duration of disease (p<3.9x10^-4), suggesting insufficient sensitivity in patients early in the disease process. Neurological signs considered as typical for NP-C were frequent (e.g., cognitive impairment 86%, ataxia 79%, vertical supranuclear gaze palsy 76%) and their presence co-occurred with accelerated diagnosis. However, less specific neuropsychiatric signs were reported to arise considerably more early in the disease process (e.g., clumsiness -4.9±1.1 y before diagnosis). Most patients showed a steady disease progression that correlated with age at neurological onset. However, a distinct subcohort (n=6) with initially steadily progressing disease later showed a 2.9-fold accelerated progression that was associated with the onset of seizures (p<7x10^-4), suggesting seizures as predictive for a poor prognosis.

Conclusions

Considering early, but less specific neuropsychiatric signs may accelerate the path to diagnosing NP-C in a patient.

【 授权许可】

   
2013 Stampfer et al.; licensee BioMed Central Ltd.

【 图 表 】

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