摘要：Introduction A reliable biomarker is urgently needed in the diagnosis and management of acid sphingomyelinase deficiency (ASMD, also known as Niemann Pick A, A/B, and B). Lyso-sphingomyelin (LSM) has previously been proposed as a biomarker for this disease. However, existing studies have not investigated the relationship between LSM levels and clinical subtype or severity. The purpose of this study is to address this gap in knowledge. Material and methods We present a cross-sectional study of 28 patients with ASMD, enrolled in an ongoing natural history study at the Icahn School of Medicine at Mount Sinai and The Children's Hospital at Montefiore. Plasma LSM levels from 28 patients were analyzed, including 7 patients with the infantile neurovisceral phenotype (ASMD type A), 3 patients with chronic neurovisceral disease (ASMD type A/B) and 18 patients with chronic visceral ASMD (ASMD type B). The association between LSM levels and clinical subtype, dichotomized as infantile (type A) or chronic (type A/B and B), was analyzed using the Wilcoxon rank sum test. In secondary analysis, the association between LSM levels and clinical severity among the chronic ASMD patients was analyzed using the Kruskal-Wallis test. Results LSM levels were elevated in all patients with ASMD when compared to a reference range of (0.04–3.8 (ng/mL)). Median LSM levels were higher in patients with infantile ASMD (386 ng/mL [314, 605]) compared to chronic ASMD (133 ng/mL [90, 209]), p < .001. Additionally, among individuals with chronic ASMD there was a positive association between LSM level and clinical severity ( p = .01, p for trend <0.001). Conclusion We identified greater LSM elevations in patients with infantile ASMD compared to those with chronic ASMD. Among patients with chronic ASMD, LSM levels were positively associated with clinical severity. These data support investigation of 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.
