Early co-occurrence of a neurologic-psychiatric disease pattern in Niemann-Pick type C disease: a retrospective Swiss cohort study

Orphanet Journal of Rare Diseases

Marianne Rohrbach⁴  Diana Ballhausen⁵  Jean-Marc Nuoffer¹  Patricie Burda⁴  Antonella Palla²  Barbara Plecko³  Lucia Abela³ 

[1] University Institute of Clinical Chemistry, University Children’s Hospital Bern, Bern, Switzerland;Department of Neurology, University Hospital Zurich, Zurich, Switzerland;Radiz–Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Zurich, Switzerland;Division of Metabolism, University Children’s Hospital Zurich, Zurich, Switzerland;Center of Molecular Diseases, University Children’s Hospital Lausanne, Lausanne, Switzerland

关键词: NP-C suspicion index;    Period prevalence rate;    Diagnostic delay;    Niemann-Pick type C;   

Others  :  1138793
DOI  :  10.1186/s13023-014-0176-7

 received in 2014-07-13, accepted in 2014-10-29,  发布年份 2014

【 摘 要 】

Background

Niemann-Pick disease type C (NP-C) is a rare autosomal recessive disorder of lysosomal cholesterol transport. The objective of this retrospective cohort study was to critically analyze the onset and time course of symptoms, and the clinical diagnostic work-up in the Swiss NP-C cohort.

Methods

Clinical, biochemical and genetic data were assessed for 14 patients derived from 9 families diagnosed with NP-C between 1994 and 2013. We retrospectively evaluated diagnostic delays and period prevalence rates for neurological, psychiatric and visceral symptoms associated with NP-C disease. The NP-C suspicion index was calculated for the time of neurological disease onset and the time of diagnosis.

Results

The shortest median diagnostic delay was noted for vertical supranuclear gaze palsy (2y). Ataxia, dysarthria, dysphagia, spasticity, cataplexy, seizures and cognitive decline displayed similar median diagnostic delays (4–5y). The longest median diagnostic delay was associated with hepatosplenomegaly (15y). Highest period prevalence rates were noted for ataxia, dysarthria, vertical supranuclear gaze palsy and cognitive decline. The NP-C suspicion index revealed a median score of 81 points in nine patients at the time of neurological disease onset which is highly suspicious for NP-C disease. At the time of diagnosis, the score increased to 206 points.

Conclusion

A neurologic-psychiatric disease pattern represents the most characteristic clinical manifestation of NP-C and occurs early in the disease course. Visceral manifestation such as isolated hepatosplenomegaly often fails recognition and thus highlights the importance of a work-up for lysosomal storage disorders. The NP-C suspicion index emphasizes the importance of a multisystem evaluation, but seems to be weak in monosymptomatic and infantile NP-C patients.

【 授权许可】

   
2014 Abela et al.; licensee BioMed Central Ltd.

【 图 表 】

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