Recommendations for the diagnosis and management of Niemann-Pick disease type C: An update

Marc C. Patterson, Christian J. Hendriksz, Mark Walterfang, Frederic Sedel, Marie T. Vanier, Frits Wijburg

Research output: Contribution to journalArticle

240 Citations (Scopus)

Abstract

Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease caused by mutations in either the NPC1 (in 95% of cases) or the NPC2 gene (in around 5% of cases), which lead to impaired intracellular lipid trafficking and accumulation of cholesterol and glycosphingolipids in the brain and other tissues. Characteristic neurological manifestations of NP-C include saccadic eye movement (SEM) abnormalities or vertical supranuclear gaze palsy (VSGP), cerebellar signs (ataxia, dystonia/dysmetria, dysarthria and dysphagia) and gelastic cataplexy. Epileptic seizures are also common in affected patients. Typically, neurological disease onset occurs during childhood, although an increasing number of cases are being detected and diagnosed during adulthood based on late-onset neurological signs and psychiatric manifestations. Categorization of patients according to age at onset of neurological manifestations (i.e. early-infantile, late-infantile, juvenile and adolescent/adult-onset) can be useful for the evaluation of disease course and treatment responses. The first international guidelines for the clinical management of NP-C in children and adults were published in 2009. Since that time a significant amount of data regarding the epidemiology, detection/diagnosis, and treatment of NP-C has been published. Here, we report points of consensus among experts in the diagnosis and treatment of NP-C based on a follow-up meeting in Paris, France in September 2011. This article serves as an update to the original guidelines providing, among other things, further information on detection/diagnostic methods, potential new methods of monitoring disease progression, and therapy. Treatment goals and the application of disease-specific therapy with miglustat are also re-evaluated.

Original languageEnglish (US)
Pages (from-to)330-344
Number of pages15
JournalMolecular Genetics and Metabolism
Volume106
Issue number3
DOIs
StatePublished - Jul 2012

Fingerprint

Type C Niemann-Pick Disease
Cerebellar Ataxia
Neurologic Manifestations
Therapeutics
Eye Abnormalities
Laughter
Cataplexy
Guidelines
Dysarthria
Glycosphingolipids
Epidemiology
Eye movements
Dystonia
Saccades
Paris
Deglutition Disorders
Age of Onset
Paralysis
France
Psychiatry

Keywords

  • Diagnosis
  • Guidelines
  • Niemann-Pick disease type C
  • Screening
  • Treatment

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Patterson, M. C., Hendriksz, C. J., Walterfang, M., Sedel, F., Vanier, M. T., & Wijburg, F. (2012). Recommendations for the diagnosis and management of Niemann-Pick disease type C: An update. Molecular Genetics and Metabolism, 106(3), 330-344. https://doi.org/10.1016/j.ymgme.2012.03.012

Recommendations for the diagnosis and management of Niemann-Pick disease type C : An update. / Patterson, Marc C.; Hendriksz, Christian J.; Walterfang, Mark; Sedel, Frederic; Vanier, Marie T.; Wijburg, Frits.

In: Molecular Genetics and Metabolism, Vol. 106, No. 3, 07.2012, p. 330-344.

Research output: Contribution to journalArticle

Patterson, MC, Hendriksz, CJ, Walterfang, M, Sedel, F, Vanier, MT & Wijburg, F 2012, 'Recommendations for the diagnosis and management of Niemann-Pick disease type C: An update', Molecular Genetics and Metabolism, vol. 106, no. 3, pp. 330-344. https://doi.org/10.1016/j.ymgme.2012.03.012
Patterson, Marc C. ; Hendriksz, Christian J. ; Walterfang, Mark ; Sedel, Frederic ; Vanier, Marie T. ; Wijburg, Frits. / Recommendations for the diagnosis and management of Niemann-Pick disease type C : An update. In: Molecular Genetics and Metabolism. 2012 ; Vol. 106, No. 3. pp. 330-344.
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