Plasma lyso-sphingomyelin levels are positively associated with clinical severity in acid sphingomyelinase deficiency

Mol Genet Metab Rep 2021 Jul 7;28:100780. doi: 10.1016/j.ymgmr.2021.100780.

PMID: 34285875

Margo Sheck Breilyn, Wenyue Zhang, Chunli Yu

Highlights: These data support investigation of lyso-sphingomyelin (LSM) as a biomarker for ASMD. Future studies are required to determine if LSM levels are predictive of phenotype in pre-symptomatic patients and how such levels correlate in response to treatment.

Abstract

Introduction: In the diagnosis and management of acid sphingomyelinase deficiency (ASMD, also known as Niemann Pick A, A/B, and B), a reliable biomarker is urgently needed. LSM, or lyso-sphingomyelin, has been recommended as a biomarker for this condition in the past. Existing research, on the other hand, hasn't looked at the link between LSM levels and clinical subtype or severity. The goal of this research is to close this information gap.

Materials and methods: We describe a cross-sectional examination of 28 ASMD patients who were part of an ongoing natural history research at Mount Sinai's Icahn School of Medicine and Montefiore's Children's Hospital. Seven patients with the infantile neurovisceral phenotype (ASMD type A), three patients with chronic neurovisceral disease (ASMD type A/B), and 18 patients with chronic visceral ASMD had their plasma LSM levels examined (ASMD type B). The Wilcoxon rank sum test was used to examine the relationship between LSM levels and clinical subtype, which was divided into infantile (type A) and chronic (type A/B and B). The Kruskal-Wallis test was used in secondary analysis to look at the relationship between LSM levels and clinical severity in chronic ASMD patients.

Results: When compared to a reference range of (0.04-3.8 (ng/mL)), LSM levels were elevated in all ASMD patients. Patients with infantile ASMD had higher median LSM levels (386 ng/mL [314, 605]) than those with chronic ASMD (133 ng/mL [90, 209]), p<.001. Furthermore, there was a positive relationship between LSM level and clinical severity in subjects with chronic ASMD (p =.01, p for trend <0.001).

Conclusion: LSM increases were found to be higher in patients with infantile ASMD than in those with chronic ASMD. LSM levels were shown to be positively linked to clinical severity in individuals with chronic ASMD. These findings support the use of LSM as an ASMD biomarker. Future research is needed to see if LSM levels might predict phenotype in pre-symptomatic patients and how these levels correlate with treatment response.

Keywords: ASM, acid sphingomyelinase, ASMD, acid sphingomyelinase deficiency, biomarker, ERT, enzyme replacement therapy, LSM, Lyso-sphingomyelin, Lysosomal storage diseases