Investigation of diagnostic performance of five urinary cholesterol metabolites for Niemann-Pick disease type C

Maekawa, Masamitsu; Jinnoh, Isamu; Narita, Aya; Iida, Takashi; Saigusa, Daisuke; Iwahori, Anna; Nittono, Hiroshi; Okuyama, Torayuki; Eto, Yoshikatsu; Ohno, Kousaku; Clayton, Peter T.; Yamaguchi, Hiroaki; Mano, Nariyasu

doi:10.1194/jlr.m093971

Cited by 21 publications

(45 citation statements)

References 26 publications

(28 reference statements)

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“…However, more recently, a larger study performed by the same research group demonstrated upregulations in 3β-sulfoxy-7βhydroxy-5-cholen-24-oic acid and its glycine and taurine conjugates, using urine samples from NPC patients (n = 23) and control (n = 28) participants [19]. A further investigation with control (n = 38) and NPC patients (n = 28) found similar findings with an AUROC value > 0.92 for 3β-sulfoxy-7β-hydroxy-5-cholen-24-oic acid, 3β-sulfoxy-7-oxo-5-cholen-24-oic acid, non-amidated 3β-sulfooxy-7β-Nacetylglucosaminyl-5-cholen-24-oic acid, glycine-amidated 3β-sulfoxy-7β-N-acetylglucosaminyl-5cholen-24-oic acid, and taurine-amidated 3β-sulfoxy-7β-N-acetylglucosaminyl-5-cholen-24-oic acid [20]. The most significant marker with an AUROC value of 1.0 was 3β-sulfooxy-7β-hydroxy-5-cholen-24-oic acid [20].…”

Section: Niemann-pick Diseasesmentioning

confidence: 99%

“…A further investigation with control (n = 38) and NPC patients (n = 28) found similar findings with an AUROC value > 0.92 for 3β-sulfoxy-7β-hydroxy-5-cholen-24-oic acid, 3β-sulfoxy-7-oxo-5-cholen-24-oic acid, non-amidated 3β-sulfooxy-7β-Nacetylglucosaminyl-5-cholen-24-oic acid, glycine-amidated 3β-sulfoxy-7β-N-acetylglucosaminyl-5cholen-24-oic acid, and taurine-amidated 3β-sulfoxy-7β-N-acetylglucosaminyl-5-cholen-24-oic acid [20]. The most significant marker with an AUROC value of 1.0 was 3β-sulfooxy-7β-hydroxy-5-cholen-24-oic acid [20]. The sensitivity and specificity of these biomarkers, and how treatments can use the biomarkers to provide diagnostic information, needs to be explored.…”

Section: Niemann-pick Diseasesmentioning

confidence: 99%

“…Typical spectra acquired are shown in Figure 2a. Average spectral intensity profiles, which show significant differences in lipoprotein-associated triacylglycerol concentrations between the two phenotypes, are depicted in Figure 2b [2] BCAAs (valine-, leucine-and isoleucine-CH 3 s); [3] vLDL/LDLbulk-chain-(-CH 2 -) n ; [4] Lactate-CH 3 ; [5] Alanine-CH 3 ; [6] lipoprotein TAG-CH 2 CH 2 CO- [7] unassigned multiplet; [8] Acetate-CH 3 [22] acute-phase glycoprotein-carbohydrate side-chain N-aceytylsugar-CH 3 /lipoprotein TAG-CH 2 -CH=CH-; [53] glutamine-β-CH 2 ; [9] lipoprotein TAG-CH 2 -CO 2 -; [54] acetone-CH 3 ; [55] acetoacetate-CH 3 ; [15] glutamine-γ-CH 2 ; [10] citrate-CH 2A/B ; [12] lipoprotein TAG-CH=CH-CH 2 -CH=CH-/citrate-CH 2A/B ; [28] albumin lysine residue-ε-CH 2 ; [21] free lysine-ε-CH 2 / creatinine-N-CH 3 /creatine-N-CH 3 ; [26] high-density-lipoprotein phospholipid choline head-group-N + (CH) 3 ; [56] β-Glucose-C2H; [24] unassigned multiplet; [11,14,17,18,25] glucose-C2-6H ring protons; [57] unassigned multiplet; [20] tyrosine-/histidine-/phenylalanine-α-CH's; [27] lactate-CH; [58] threonine-α-CH; [59] β-glucose-C1H; [60] α-glucose-C1H; [61] lipoprotein TAG-CH=CH-; [62] urea-CO-NH 2 ; [29,30] tyrosine aromatic-CH protons; [33,41] histidine-imidazole ring-CHs;…”

Section: Gm1 Gm2 and Gm3 Gangliosidosesmentioning

confidence: 99%

“…For the purpose of this review, NPC1 will be considered as a sphingolipidosis, because in addition to cholesterol it accumulates sphingolipids, and since it shares symptoms and pathogenic mechanisms with the sphingolipidoses Niemann-Pick types A and B. ↑ 3β-Sulfooxy-7β-hydroxy-5cholen-24-oic acid, 3β-sulfooxy-7-oxo-5-cholen-24-oic acid, non-amidated 3βsulfooxy-7β-Nacetylglucosaminyl-5-cholen-24-oic acid, glycine-amidated 3β-sulfooxy-7β-Nacetylglucosaminyl-5-cholen-24-oic acid and taurine-amidated 3β-sulfooxy-7β-Nacetylglucosaminyl-5-cholen-24-oic acid AUROC value > 0.92 for each marker AUROC value 1.0 for 3β-sulfooxy-7β-N-acetylglucosaminyl-5-cholen-24-oic acid [20] Human Glycosylceramide p = 0.0327 and Glysocylcarmide/ceramide ratio p = 0.0034 after 6 months after receiving ERT/SRT.…”

Section: Introductionmentioning

confidence: 99%

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Metabolomic Studies of Lipid Storage Disorders, with Special Reference to Niemann-Pick Type C Disease: A Critical Review with Future Perspectives

Percival

Gibson

Wilson

et al. 2020

IJMS

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Lysosomal storage disorders (LSDs) are predominantly very rare recessive autosomal neurodegenerative diseases.Sphingolipidoses, a sub-group of LSDs, result from defects in lysosomal enzymes involved in sphingolipid catabolism, and feature disrupted storage systems which trigger complex pathogenic cascades with other organelles collaterally affected. This process leads to cell dysfunction and death, particularly in the central nervous system. One valuable approach to gaining insights into the global impact of lysosomal dysfunction is through metabolomics, which represents a discovery tool for investigating disease-induced modifications in the patterns of large numbers of simultaneously-analysed metabolites, which also features the identification of biomarkers Here, the scope and applications of metabolomics strategies to the investigation of sphingolipidoses is explored in order to facilitate our understanding of the biomolecular basis of these conditions. This review therefore surveys the benefits of applying ’state-of-the-art’ metabolomics strategies, both univariate and multivariate, to sphingolipidoses, particularly Niemann-Pick type C disease. Relevant limitations of these techniques are also discussed, along with the latest advances and developments. We conclude that metabolomics strategies are highly valuable, distinctive bioanalytical techniques for probing LSDs, most especially for the detection and validation of potential biomarkers. They also show much promise for monitoring disease progression and the evaluation of therapeutic strategies and targets.

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Section: Niemann-pick Diseasesmentioning

confidence: 99%

Section: Niemann-pick Diseasesmentioning

confidence: 99%

Section: Gm1 Gm2 and Gm3 Gangliosidosesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Metabolomic Studies of Lipid Storage Disorders, with Special Reference to Niemann-Pick Type C Disease: A Critical Review with Future Perspectives

Percival

Gibson

Wilson

et al. 2020

IJMS

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“…A simultaneous analytical method for SNAG-Δ 5 -CA, SNAG-Δ 5 -CG, SNAG-Δ 5 -CT, S7B-Δ 5 -CA, and S7O-Δ 5 -CA in urine was developed using LC/MS/MS, and its diagnostic performance for NPC was evaluated [83]. Along with other previous reports [66,67,81,82], a LC/ESI-MS/MS system equipped with a column switching system was used.…”

Section: Abnormal Cholenoic Acidsmentioning

confidence: 99%

Identification and Evaluation of Biomarkers for Niemann-Pick Disease Type C Based on Chemical Analysis Techniques

Maekawa

Mano

2020

Chromatography

Self Cite

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Niemann-Pick disease type C (NPC) is an autosomal recessive disorder that features progressive neurodegeneration. Because NPC patients have mutations in NPC1 or NPC2 cholesterol transporting proteins, failures in cholesterol and other lipid trafficking occur. NPC patients represent a wide clinical spectrum in terms of age of onset and type of symptoms. Because conventional diagnostic methods are time-consuming and complicated, biomarker tests have attracted increased attention. In this review, recently reported biomarkers for NPC are discussed in detail. For example, oxysterols and some cholenoic acid conjugates, metabolized from excess cholesterol in NPC cells, can be detected in urine or plasma. In addition, two types of lysosphingolipids, sphingosylphosphorylcholine and glycosylsphingosine, are present at increased concentrations in NPC patients.A more recently discovered biomarker is N-palmitoyl-O-phosphorylcholine, previously called "lysosphingomyelin-509." These biomarkers are helpful for the early diagnosis of NPC and may contribute to a good prognosis for NPC patients.

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Importance of the biochemical investigations for the functional characterization of a NPC1 variant identified by exome sequencing

Almenabawy,

Hung,

Sosova

et al. 2024

American J of Med Genetics Pt A

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Niemann–Pick disease type C (NPC) is one of the lysosomal storage disorders. It is caused by biallelic pathogenic variants in NPC1 or NPC2, which results in a defective cholesterol trafficking inside the late endosome and lysosome. There is a high clinical variability in the age of presentation and the phenotype of this disorder making the diagnosis challenging. Here, we report a patient with an infantile onset global developmental delay, microcephaly and dysmorphic features, homozygous for c.3560C>T (p.A1187V) variant in NPC1. His plasma oxysterol levels were normal on two occasions. His lyso‐sphingomyelin‐509 (lyso‐SM 509) and urinary bile acid levels were normal. Based on the phenotype and biochemical features, the diagnosis of NPC was excluded in this patient. We emphasize the importance of functional characterization in the classification of novel variants to prevent a misdiagnosis. Matching the phenotype and biochemical evidence with the molecular genomic tests is crucial for the confirmation of genetic diagnoses.

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Investigation of diagnostic performance of five urinary cholesterol metabolites for Niemann-Pick disease type C

Cited by 21 publications

References 26 publications

Metabolomic Studies of Lipid Storage Disorders, with Special Reference to Niemann-Pick Type C Disease: A Critical Review with Future Perspectives

Metabolomic Studies of Lipid Storage Disorders, with Special Reference to Niemann-Pick Type C Disease: A Critical Review with Future Perspectives

Identification and Evaluation of Biomarkers for Niemann-Pick Disease Type C Based on Chemical Analysis Techniques

Importance of the biochemical investigations for the functional characterization of a NPC1 variant identified by exome sequencing

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