Plasma lysosphingomyelin demonstrates great potential as a diagnostic biomarker for Niemann–Pick disease type C in a retrospective study

Welford, Richard W. D.; Garzotti, Marco; Lourenço, Charles Marques; Mengel, Eugen; Marquardt, Thorsten; Amraoui, Yasmina; Kolb, Stefan; Morand, Olivier; Groenen, Peter M.A.

doi:10.1016/j.ymgme.2014.12.289

Cited by 9 publications

(18 citation statements)

References 31 publications

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“…Accumulation of sphingomyelin in Npc1 nih liver has been extensively documented [24,54,56]. Npc1 Recently increased levels of GlcSph have been reported in NPC patient cohorts [57,58]. Our investigation confirms that the lyso-GSL tends to be elevated in the majority of patients analyzed.…”

Section: Modelsupporting

confidence: 79%

“…Our investigation confirms that the lyso-GSL tends to be elevated in the majority of patients analyzed. Recently, elevations in phosphorylcholinesphingosine (deacylated sphingomyelin, lysoSM) and in the isoform lysoSM-509 were described in plasma of NPC patients [57,59]. Plasma oxysterols have earlier been validated as sensitive biomarker for NPC [30,60].…”

Section: Modelmentioning

confidence: 99%

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Lyso-glycosphingolipid abnormalities in different murine models of lysosomal storage disorders

Ferraz

Marques

Gaspar

et al. 2016

Molecular Genetics and Metabolism

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Section: Modelsupporting

confidence: 79%

Section: Modelmentioning

confidence: 99%

Lyso-glycosphingolipid abnormalities in different murine models of lysosomal storage disorders

Ferraz

Marques

Gaspar

et al. 2016

Molecular Genetics and Metabolism

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“…Median LysoSM levels in NPC patients, for whom LysoSM was recently proposed as additional biomarker [12], were significantly higher (by 3.4-fold) compared to controls. A significant but less pronounced increase was observed in GD (p < 0.0001) and FD patients (p = 0.0062) where levels were progressively reduced compared to NPC.…”

Section: Lysosls In Healthy Controls and Patients With Lsdmentioning

confidence: 85%

“…Carryover was also evaluated by injections of blank samples after the highest point of calibration. Since the short-term stability of LysoSLs in plasma has been reported in literature [7,12], we assessed the long-term stability in a plasma sample from a healthy donor. The stability of analytes in pooled plasma after freeze/thaw cycles and in reconstituted solutions left in the HPLC autosampler (10 °C) for 24 h was also assessed.…”

Section: Methods Validationmentioning

confidence: 99%

“…Two hexosylsphingosines (HexSph), galactosylsphingosine (GalSph) and glucosylsphingosine (GlcSph), respectively, were increased in patients with KD [9,10] and GD [4]. The deacetylated form of sphingomyelin, lysosphingomyelin (LysoSM) is elevated in NPA/B and NPC [11,12]. Recently, a novel biomarker, lyso-sphingomyelin-509 (LysoSM-509), has been established for the primary diagnosis of NPC [13].…”

Section: Introductionmentioning

confidence: 99%

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Diagnosis of sphingolipidoses: a new simultaneous measurement of lysosphingolipids by LC-MS/MS

Polo

Burlina

Kolamunnage

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background: Lysosphingolipids (LysoSLs) are derivatives of sphingolipids which have lost the amide-linked acyl chain. More recently, LysoSLs have been identified as storage compounds in several sphingolipidoses, including Gaucher, Fabry and Niemann-Pick diseases. To date, different methods have been developed to measure each individual lysosphingolipid in plasma. This report describes a rapid liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) assay for simultaneous quantification of several LysoSLs in plasma. Methods: We analyzed the following compounds: hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), lysosphingomyelin (LysoSM) and lysosphingomyelin-509 (LysoSM-509). The sample preparation requires only 100 μL of plasma and consists of an extraction with a mixture of MeOH/acetone/H 2 O (45:45:10, v/v). Results: The method validation showed high sensitivity, an excellent accuracy and precision. Reference ranges were determined in healthy adult and pediatric

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Diagnostic workup and management of patients with suspected Niemann-Pick type C disease

Papandreou

Gissen

2016

Ther Adv Neurol Disord

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Niemann-Pick type C (NP-C) disease is a neurovisceral disorder caused by mutations in the NPC1 and NPC2 genes. It is characterized by lysosomal storage of a broad range of lipids as a result of abnormal intracellular lipid trafficking. Typically patients develop neurodegeneration; however, the speed of disease progression is variable. The exact functions of NPC1 and NPC2 proteins have not been determined and therefore the molecular pathophysiology of NP-C is still not clearly understood. Due to the disease's rarity and clinical heterogeneity, delays from symptom onset to diagnosis and treatment initiation are common. Current therapeutic approaches focus on multidisciplinary symptom control and deceleration (rather than reversal) of disease progression. Thus identification of cases at early stages of disease is particularly important. Recent advances in genetic and biochemical testing have resulted in the generation of relatively non-invasive, quick and cost-effective laboratory assays that are highly sensitive and specific and have the capacity to enhance the clinicians' ability to reach a diagnosis earlier. Miglustat is a compound recently licensed in many countries for the treatment of NP-C that has been shown to decelerate neurological regression, whereas many other promising drugs are currently being trialled in preclinical models or human studies. This review summarizes key clinical, genetic and biochemical features of NP-C, suggests a simple diagnostic investigation strategy and gives an overview of available therapeutic options as well as potential novel treatments currently under development.

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Plasma lysosphingomyelin demonstrates great potential as a diagnostic biomarker for Niemann–Pick disease type C in a retrospective study

Cited by 9 publications

References 31 publications

Lyso-glycosphingolipid abnormalities in different murine models of lysosomal storage disorders

Lyso-glycosphingolipid abnormalities in different murine models of lysosomal storage disorders

Diagnosis of sphingolipidoses: a new simultaneous measurement of lysosphingolipids by LC-MS/MS

Diagnostic workup and management of patients with suspected Niemann-Pick type C disease

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