Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
PPGMB, UFRGS, Porto Alegre, Brazil.
Orphanet J Rare Dis. 2022 Nov 8;17(1):407. doi: 10.1186/s13023-022-02560-x.
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).
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.
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.
酸性鞘磷脂酶缺乏症（ASMD）是一种溶酶体疾病，由酸性鞘磷脂酶（ASM）缺乏引起，导致鞘磷脂（SM）在多种细胞类型中积累。神经酰胺酶（LysoSM）是 SM 的去乙酰化形式，已被证明是组织、血浆和干血斑（DBS）中 ASMD 的生物标志物，而神经酰胺酶 509（LysoSM509）是 LysoSM 的羧基类似物。ASMD 患者的 LysoSM509 水平也很高。在这项研究中，我们报告了通过超高效液相色谱串联质谱（UPLC-MS/MS）定量分析拉丁美洲 ASMD 患者 DBS 中 LysoSM 和 LysoSM509 的效用。
将 14 名 ASMD 患者的 DBS 样本与 15 名对照和 44 名普通新生儿进行比较。所有患者的 ASM 定量和壳三糖苷酶活性测量均证实了他们的诊断。与对照组和普通新生儿相比，所有患者的 LysoSM 和 LysoSM509 水平均显著升高。
DBS 中神经鞘脂的定量分析是诊断 ASMD 患者的一种有价值的工具，而 LysoSM 可用于与 NPC 的鉴别诊断。该方法在 ASMD 新生儿筛查过程中也很有价值。
