Quantitation of plasmatic lysosphingomyelin and lysosphingomyelin-509 for differential screening of Niemann-Pick A/B and C diseases

Kuchař, Ladislav; Sikora, Jakub; Gulinello, Maria; Poupětová, Helena; Ługowska, Agnieszka; Malinová, Věra; Jahnová, Helena; Asfaw, Befekadu; Ledvinová, Jana

doi:10.1016/j.ab.2017.02.019

Cited by 58 publications

(70 citation statements)

References 25 publications

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“…The structure is not precisely known, and LysoSM509 lacks a standard and a stable isotopelabeled IS; thus, validation of quantification cannot be completely obtained. All reports agree that LysoSM509 is dramatically elevated in NPC and NPAB (Polo et al 2017;Kuchar et al 2017;Pettazzonietal.2017). Results could have been reported in concentration (Giese et al 2015, Kuchar et al 2017), but expression as MoM of controls (Polo et al 2017) should be preferred in the absence of standard and specific IS.…”

Section: Lysosphingolipidsmentioning

confidence: 60%

“…All reports agree that LysoSM509 is dramatically elevated in NPC and NPAB (Polo et al 2017;Kuchar et al 2017;Pettazzonietal.2017). Results could have been reported in concentration (Giese et al 2015, Kuchar et al 2017), but expression as MoM of controls (Polo et al 2017) should be preferred in the absence of standard and specific IS. We confirm a dramatic increase of LysoSM509 in all our NPAB patients (n = 24) and in young NPC patients (<10 years, n =24 (Fig.…”

Section: Lysosphingolipidsmentioning

confidence: 60%

“…Thus, NPAB screening with LysoSM measurement seems to be interesting but insufficient in some cases. Besides, Kuchar et al (2017) found no increase of LysoSM in DBS of NPAB patients. In addition, it can be slightly increased in NPC: a 2.8-fold increase of LysoSM in plasma of NPC patients was reported (Welford et al 2014)and confirmed by others.…”

Section: Lysosphingolipidsmentioning

confidence: 83%

“…2). However, recently, Kuchar et al (2017) reported normal plasma LysoSM in a 63-year-old patient affected with a very mild form of NPB (homozygous for the mutation p.Arg289His in the SMPD1 gene); thus, the sensitivity of this biomarker seems to be incomplete. We also observed a very moderate increase in plasma LysoSM (2.4 and 2.5 nmol/L; controls, < 1.1 nmol/L) in two young NPB patients (2 and 3 years old).…”

Section: Lysosphingolipidsmentioning

confidence: 98%

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Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders

Piraud

Pettazzoni

Lavoie

et al. 2018

J of Inher Metab Disea

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Tandem mass spectrometry (MS/MS) is a highly sensitive and specific technique. Thanks to the development of triple quadrupole analyzers, it is becoming more widely used in laboratories working in the field of inborn errors of metabolism. We review here the state of the art of this technique applied to the diagnosis of lysosomal storage disorders (LSDs) and how MS/MS has changed the diagnostic rationale in recent years. This fine technology brings more sensitive, specific, and reliable methods than the previous biochemical ones for the analysis of urinary glycosaminoglycans, oligosaccharides, and sialic acid. In sphingolipidoses, the quantification of urinary sphingolipids (globotriaosylceramide, sulfatides) is possible. The measurement of new plasmatic biomarkers such as oxysterols, bile acids, and lysosphingolipids allows the screening of many sphingolipidoses and related disorders (Niemann-Pick type C), replacing tedious biochemical techniques. Applied to amniotic fluid, a more reliable prenatal diagnosis or screening of LSDs is now available for fetuses presenting with antenatal manifestations. Applied to enzyme measurements, it allows high throughput assays for the screening of large populations, even newborn screening. The advent of this new method can modify the diagnostic rationale behind LSDs.

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Section: Lysosphingolipidsmentioning

confidence: 60%

Section: Lysosphingolipidsmentioning

confidence: 60%

Section: Lysosphingolipidsmentioning

confidence: 83%

Section: Lysosphingolipidsmentioning

confidence: 98%

See 2 more Smart Citations

Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders

Piraud

Pettazzoni

Lavoie

et al. 2018

J of Inher Metab Disea

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“…Multiplex analyses of Lyso-SM-509 were useful for differentiation from other lysosomal diseases [98]. The differentiation between NPC and NP-A/B [99,100] and correlations between cholenoic acids and Lyso-SM-509 have also been reported [101]. However, these reports are did not use authentic standards, and are semi-quantitative studies that cannot be applied as chemical diagnostics.…”

Section: N-palmitoyl-o-phosphocholine-serine Previously Referred To mentioning

confidence: 99%

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

Maekawa

Mano

2020

Chromatography

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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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Skin inflammation and impaired adipogenesis in a mouse model of acid ceramidase deficiency

Rybová

Kuchař

Sikora

et al. 2022

J of Inher Metab Disea

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Acid ceramidase catalyzes the degradation of ceramide into sphingosine and a free fatty acid. Acid ceramidase deficiency results in lipid accumulation in many tissues and leads to the development of Farber disease (FD). Typical manifestations of classical FD include formation of subcutaneous nodules and joint contractures as well as the development of a hoarse voice. Healthy skin depends on a unique lipid profile to form a barrier that confers protection from pathogens, prevents excessive water loss, and mediates cell-cell communication. Ceramides comprise $50% of total epidermis lipids and regulate cutaneous homeostasis and inflammation. Abnormal skin development including visual skin lesions has been reported in FD patients, but a detailed study of FD skin has not been performed. We conducted a pathophysiological study of the skin in our mouse model of FD. We observed altered lipid composition in FD skin dominated by accumulation of all studied ceramide species and buildup of abnormal storage structures affecting mainly the dermis. A deficiency of acid ceramidase activity also led to the activation of inflammatory IL-6/JAK/signal transducer and activator of transcription 3 and noncanonical NF-κB signaling pathways. Last, we report reduced proliferation of FD mouse fibroblasts and adipose-derived stem/stromal cells (ASC) along with impaired differentiation of ASCs into mature adipocytes.

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Quantitation of plasmatic lysosphingomyelin and lysosphingomyelin-509 for differential screening of Niemann-Pick A/B and C diseases

Cited by 58 publications

References 25 publications

Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders

Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders

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

Skin inflammation and impaired adipogenesis in a mouse model of acid ceramidase deficiency

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