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
| Autor: | Andrea Dardis, Agata Fiumara, Stefania Zampieri, Francesco Brancati, Milena Romanello, Annalisa Sechi, Rossella Parini, Laura Deroma, Bruno Bembi, Barbara Borroni, Amalia C. Bruni, Nadia Bortolotti, Cinzia Valeria Russo, Andrea Bordugo |
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| Přispěvatelé: | Romanello, M., Zampieri, S., Bortolotti, N., Deroma, L., Sechi, A., Fiumara, A., Parini, R., Borroni, B., Brancati, F., Bruni, A., Russo, C. V., Bordugo, A., Bembi, B., Dardis, A. |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Clinical Biochemistry Hepatosplenomegaly Liquid chromatography-tandem-mass spectrometry Niemann-Pick Oxysterols Variant biochemical phenotype Calibration Carrier Proteins Cholestanes Cohort Studies Humans Italy Ketocholesterols Membrane Glycoproteins Niemann-Pick Diseases Reproducibility of Results Sphingomyelin Phosphodiesterase Mutation Biochemistry Biochemistry (medical) Context (language use) Disease Liquid chromatography-tandem–mass spectrometry 03 medical and health sciences Oxysterol 0302 clinical medicine Oxysterols Niemann-Pick Niemann-Pick C1 Protein Internal medicine medicine Chemistry Intracellular Signaling Peptides and Proteins General Medicine medicine.disease Phenotype 030104 developmental biology Immunology Cohort lipids (amino acids peptides and proteins) Differential diagnosis medicine.symptom NPC1 Niemann–Pick disease 030217 neurology & neurosurgery |
| Popis: | Niemann-Pick C disease (NPCD) is a rare autosomal recessive neurovisceral disorder with a heterogeneous clinical presentation. Cholestan-3β,5α,6β-triol and 7-ketocholesterol have been proposed as biomarkers for the screening of NPCD. In this work, we assessed oxysterols levels in a cohort of Italian patients affected by NPCD and analyzed the obtained results in the context of the clinical, biochemical and molecular data. In addition, a group of patients affected by Niemann-Pick B disease (NPBD) were also analyzed. NPC patients presented levels of both oxysterols way above the cut off value, except for 5 siblings presenting the variant biochemical phenotype who displayed levels of 3β,5α,6β-triol below or just above the cut-off value; 2 of them presented also normal levels of 7-KC. Both oxysterols were extremely high in a patient presenting the neonatal systemic lethal phenotype. All NPB patients showed increased oxysterols levels. In conclusion, the reported LC-MS/MS assay provides a robust non-invasive screening tool for NPCD. However, false negative results can be obtained in patients expressing the variant biochemical phenotype. These data strengthen the concept that the results should always be interpreted in the context of the patients' clinical picture and filipin staining and/or genetic studies might still be undertaken in patients with normal levels of oxysterols if symptoms are highly suggestive of NPCD. Both oxysterols are significantly elevated in NPB patients; thus a differential diagnosis should always be performed in patients presenting isolated hepatosplenomegaly, a common clinical sign of both NPCD and NPBD. |
| Databáze: | OpenAIRE |
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