+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Niemann-Pick Type C-2 Disease: Identification by Analysis of Plasma Cholestane-3β,5α,6β-Triol and Further Insight into the Clinical Phenotype



Niemann-Pick Type C-2 Disease: Identification by Analysis of Plasma Cholestane-3β,5α,6β-Triol and Further Insight into the Clinical Phenotype



Jimd Reports 23: 17-26



Niemann-Pick type C disease is a rare disorder caused by impaired intracellular lipid transport due to mutations in either the NPC1 or the NPC2 gene. Ninety-five % of NPC patients show mutations in the NPC1 gene. A much smaller number of patients suffer from NPC2 disease and present respiratory failure as one of the most frequent symptoms. Several plasma oxysterols are highly elevated in NPC1 and can be used as a biomarker in the diagnosis of NPC1. Plasma cholestane-3β,5α,6β-triol was evaluated as biomarker for NPC2 by GC/MS and LC-MS/MS analysis. The diagnosis was confirmed by Sanger sequencing and filipin staining. We report three NPC2 patients with typical respiratory problems and a detailed description of the nature of the lung disease in one of them. All patients had elevated levels of plasma cholestane-3β,5α,6β-triol. In two of these patients, the positive oxysterol result led to a rapid diagnosis of NPC2 by genetic analysis. The phenotype of the third patient has been described previously. In this patient a cholestane-3β,5α,6β-triol concentration markedly above the reference range was found. Measurement of plasma cholestane-3β,5α,6β-triol enables to discriminate between controls and NPC1 and NPC2 patients, making it a valuable biomarker for the rapid diagnosis not only for NPC1 but also for NPC2 disease.The measurement of oxysterols should be well kept in mind in the differential diagnosis of lysosomal diseases, as the elevation of oxysterols in plasma may speed up the diagnosis of NPC1 and NPC2.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 058408743

Download citation: RISBibTeXText

PMID: 25772320

DOI: 10.1007/8904_2015_423


Related references

Determination of serum cholestane-3β,5α,6β-triol by gas chromatography-mass spectrometry for identification of Niemann-Pick type C (NPC) disease. Journal of Steroid Biochemistry and Molecular Biology 169: 54-60, 2016

Selective screening of Niemann-Pick type C Brazilian patients by cholestane-3β,5α,6β-triol and chitotriosidase measurements followed by filipin staining and NPC1/NPC2 gene analysis. Clinica Chimica Acta; International Journal of Clinical Chemistry 459: 57-62, 2017

Cholestane-3β,5α,6β-triol: high levels in Niemann-Pick type C, cerebrotendinous xanthomatosis, and lysosomal acid lipase deficiency. Journal of Lipid Research 56(10): 1926-1935, 2016

Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients. Journal of Clinical Investigation 88(3): 806-810, 1991

Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1. Human Mutation 22(4): 313-325, 2003

Quantitative proteomic analysis of Niemann-Pick disease, type C1 cerebellum identifies protein biomarkers and provides pathological insight. Plos One 7(10): E47845, 2014

A C57BL/KsJ mouse model of Niemann-Pick disease (spm) belongs to the same complementation group as the major childhood type of Niemann-Pick disease type C. Human Genetics 99(3): 350-353, 1997

Clinical features of Niemann-Pick disease type C. An example of the delayed onset, slowly progressive phenotype and an overview of recent literature. Clinical Neurology and Neurosurgery 96(2): 119-123, 1994

A mouse model of niemann pick disease ii complementation analysis between the 3t3 cells and cells from niemann pick disease type c and i cell disease. American Journal of Human Genetics 49(4 Suppl.): 125, 1991

Comprehensive Evaluation of Plasma 7-Ketocholesterol and Cholestan-3β,5α,6β-Triol in an Italian Cohort of Patients Affected by Niemann-Pick Disease due to NPC1 and SMPD1 Mutations. Clinica Chimica Acta; International Journal of Clinical Chemistry 455: 39-45, 2016

Microarray expression analysis and identification of serum biomarkers for Niemann-Pick disease, type C1. Human Molecular Genetics 21(16): 3632-3646, 2013

Genotype-phenotype relationship of Niemann-Pick disease type C: A possible correlation between clinical onset and levels of NPC1 protein in isolated skin fibroblasts. Journal of Medical Genetics 37(9): 707-711, 2000

Genotype-phenotype relationship of Niemann-Pick disease type C: a possible correlation between clinical onset and levels of NPC1 protein in isolated skin fibroblasts. Journal of Medical Genetics 37(9): 707-712, 2001

Auditory phenotype of Niemann-Pick disease, type C1. Ear and Hearing 35(1): 110-117, 2014

Identification and analysis of the S cerevisiae homologues of the Niemann-Pick Type C disease genes, hNPC1 and hHE1. Molecular Biology of the Cell 13(Suppl.): 541a, 2002