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. 2022 Nov 8;17(1):407.
doi: 10.1186/s13023-022-02560-x.

Quantification of lysosphingomyelin and lysosphingomyelin-509 for the screening of acid sphingomyelinase deficiency

Francyne Kubaski  1   2 , Alberto Burlina  3 , Danilo Pereira  4   5 , Camilo Silva  4 , Zackary M Herbst  6 , Franciele B Trapp  1 , Kristiane Michelin-Tirelli  1 , Franciele F Lopes  1 , Maira G Burin  1 , Ana Carolina Brusius-Facchin  1 , Alice B O Netto  1   2 , Edina Poletto  1   2 , Tamires M Bernardes  7 , Gerson S Carvalho  8 , Ney B Sorte  9 , Fernanda N Ferreira  10 , Nilza Perin  11 , Marta R Clivati  12 , Marnie T S de Santana  13 , Sandra F G Lobos  14 , Emilia K E A Leão  9 , Marcelo P Coutinho  15 , Paola V Pinos  16 , Maria L S F Santos  17 , Debora A Penatti  17 , Charles M Lourenço  18 , Giulia Polo  19 , Roberto Giugliani  1   2   20   21
Affiliations

Quantification of lysosphingomyelin and lysosphingomyelin-509 for the screening of acid sphingomyelinase deficiency

Francyne Kubaski et al. Orphanet J Rare Dis. .

Abstract

Background: Acid sphingomyelinase deficiency (ASMD) is a lysosomal disorder caused by deficiency of acid sphingomyelinase (ASM) leading to the accumulation of sphingomyelin (SM) in a variety of cell types. Lysosphingomyelin (LysoSM) is the de-acetylated form of SM and it has been shown as a biomarker for ASMD in tissues, plasma, and dried blood spots (DBS) and lysosphingomyelin-509 (LysoSM509) is the carboxylated analogue of LysoSM. High levels of Lysosphingomyelin 509 (LysoSM509) have also been shown in ASMD patients. In this study, we report the utility of the quantification of LysoSM and LysoSM509 in DBS of patients from Latin America with ASMD by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).

Results: DBS samples from 14 ASMD patients were compared with 15 controls, and 44 general newborns. All patients had their diagnosis confirmed by the quantification of ASM and the measurement of the activity of chitotriosidase. All patients had significantly higher levels of lysoSM and lysoSM509 compared to controls and general newborns.

Conclusions: The quantification of lysosphingolipids in DBS is a valuable tool for the diagnosis of ASMD patients and lysoSM can be useful in the differential diagnosis with NPC. This method is also valuable in the ASMD newborn screening process.

Keywords: Acid sphingomyelinase deficiency; Biomarker; Lysosphingomyelin; Niemann-Pick type a/b; Tandem mass spectrometry.

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Conflict of interest statement

The authors have no competing interests to declare.

Figures

Fig. 1
Fig. 1
A Distribution of lysoSM in ASMD patients, controls, and general newborns according to age. B Median levels of lysoSM in ASMD patients, controls, and general newborns with a 95% confidence interval
Fig. 2
Fig. 2
A Distribution of lysoSM509 in ASMD patients, controls, and general newborns according to age. B Median levels of lysoSM509 in ASMD patients, controls, and general newborns with a 95% confidence interval
Fig. 3
Fig. 3
Pearson’s correlation of the lysoSM x lysoSM509 in ASMD patients, controls, and general newborns
See this image and copyright information in PMC

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