Plasma lyso-sphingomyelin levels are positively associated with clinical severity in acid sphingomyelinase deficiency.
Plasma lyso-sphingomyelin levels are positively associated with clinical severity in acid sphingomyelinase deficiency.
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血浆溶血鞘磷脂水平与酸性鞘磷脂酶缺乏症的临床严重程度呈正相关。
DOI：
10.1016/j.ymgmr.2021.100780
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发表时间：
2021-09
影响因子：
1.9
通讯作者：
Wasserstein MP
中科院分区：
文献类型：
--
作者：
Breilyn MS;Zhang W;Yu C;Wasserstein MP
酸性鞘磷脂酶缺乏症(ASMD，也称为Niemann Pick A、A/B和B)的诊断和治疗迫切需要可靠的生物标志物。溶血鞘磷脂(LSM)此前已被认为是该病的生物标志物。然而，现有的研究还没有研究LSM水平与临床亚型或严重程度的关系。这项研究的目的是解决这一知识差距。我们介绍了一项对28名ASMD患者的横断面研究，这些患者在西奈山的伊坎医学院和蒙特菲奥雷的儿童医院参加了一项正在进行的自然历史研究。分析28例患者的血浆LSM水平，包括7例婴幼儿神经内脏表型(ASMD A型)、3例慢性神经内脏病(ASMD A/B型)和18例慢性内脏ASMD(ASMD B型)。用Wilcoxon秩和检验分析LSM水平与临床亚型(分为婴儿型(A型)或慢性(A/B和B型))之间的关系。在二次分析中，使用Kruskal-Wallis检验分析了慢性ASMD患者LSM水平与临床严重程度之间的关系。与参考范围(0.04-3.8(ng/mL))相比，所有ASMD患者LSM水平均升高。婴儿型ASMD患者的LSM水平中位数(386 ng/mL[314,605])高于慢性ASMD患者(133 ng/mL[90,209])，p<0.01。此外，在慢性ASMD患者中，LSM水平与临床严重程度呈正相关(p=0.01，p为Trend<；0.001)。我们发现，与慢性ASMD患者相比，婴儿ASMD患者的LSM升高更大。在慢性ASMD患者中，LSM水平与临床严重程度呈正相关。这些数据支持将LSM作为ASMD的生物标志物的研究。需要进一步的研究来确定LSM水平是否可以预测症状前患者的表型，以及这些水平如何与治疗反应相关。溶血鞘磷脂(LSM)已被认为是酸性鞘磷脂酶缺乏症(ASMD)的生物标志物。现有研究尚未探讨LSM升高程度与临床亚型或严重程度之间的关系。我们介绍了一项正在进行的自然病史研究中登记的28名ASMD患者的横断面研究。与参考范围相比，所有ASMD患者的LSM水平均升高。婴儿型ASMD患者的LSM水平中位数高于慢性ASMD患者。在慢性ASMD患者中，LSM水平与临床严重程度呈正相关。
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. 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. 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). 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. Lyso-sphingomyelin (LSM) has previously been proposed as a biomarker for acid sphingomyelinase deficiency (ASMD). Existing studies have not investigated the relationship between degree of LSM elevation and clinical subtype or severity. We present a cross-sectional study of 28 patients with ASMD enrolled in an ongoing natural history study. LSM levels were elevated in all patients with ASMD compared to reference ranges. Median LSM levels were higher in patients with infantile ASMD compared to chronic ASMD. Among individuals with chronic ASMD, there was a positive association between LSM level and clinical severity.
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影响因子：
12.8
作者：
Murugesan V;Chuang WL;Liu J;Lischuk A;Kacena K;Lin H;Pastores GM;Yang R;Keutzer J;Zhang K;Mistry PK
通讯作者：
Mistry PK
影响因子：
5.1
作者：
Burton, Barbara K.;Charrow, Joel;Dizikes, George
通讯作者：
Dizikes, George
影响因子：
4.2
作者：
Wasserstein MP;Diaz GA;Lachmann RH;Jouvin MH;Nandy I;Ji AJ;Puga AC
通讯作者：
Puga AC
影响因子：
6.8
作者：
Polo, Giulia;Burlina, Alessandro P.;Burlina, Alberto B.
通讯作者：
Burlina, Alberto B.
影响因子：
3.8
作者：
Schuchman EH;Desnick RJ
通讯作者：
Desnick RJ