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

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.

Plasma lysosphingolipids in GRN-related diseases: Monitoring lysosomal dysfunction to track disease progression

“…Thus, increased levels of those analytes are not common to all forms of FTD, nor are they linked to abnormal neuronal TDP-43 aggregation, but rather lysoSPL elevation more likely represents a process related to GRN haploinsufficiency. Importantly, there was no association between lysoSPL and age at sampling in controls, as previous works already pointed out (Murugesan et al, 2016;Kubaski et al, 2022). Taken together, these observations suggest that the increase of lysosomal storage products is not related to normal ageing, but could be triggered by PGRN deficiency.…”

Gaucher Disease or Acid Sphingomyelinase Deficiency? The Importance of Differential Diagnosis

“…Detection of glucosylsphingosine (Lyso-Gb1), lysosphingomyelin-509 (Lyso SM-509) and lysosphingomyelin (Lyso SM) was performed in dried blood spots using the LC-MS/MS technique [ 21 , 22 , 23 , 24 , 25 , 26 ].…”

Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann–Pick disease types A, B and A/B)

“…Thus far, exact quantifications of PPCS in ASMD patients using homemade standards (in genuine nmol/L) have only been reported from Ory’s and Maekawa’s groups, respectively [ 89 , 90 ]. Determination of lyso-SM and PPCS is also possible in DBS although less discriminative than in plasma [ 77 , 91 , 92 ].…”