TY - JOUR
T1 - Plasma lyso-sphingomyelin levels are positively associated with clinical severity in acid sphingomyelinase deficiency
AU - Breilyn, Margo Sheck
AU - Zhang, Wenyue
AU - Yu, Chunli
AU - Wasserstein, Melissa P.
N1 - Funding Information:
The research described was supported by NIH/National Center for Advancing Translational Science (NCATS) Einstein-Montefiore CTSA Grant Number UL1TR001073 and the National Niemann Pick Disease Foundation (NNPDF).
Funding Information:
Margo Breilyn, Wenyue Zhang and Chunli Yu have no financial disclosures or conflicts of interest. Melissa Wasserstein has received consultant fees, travel reimbursement, and research support from Sanofi Genzyme, consultant fees from Takeda, and research support from Alexion, the Ara Parseghian Medical Research Fund, BioMarin, Cure Sanfilippo Foundation, Firefly Fund, National Niemann Pick Disease Foundation, Orchard Therapeutics, PassageBio, Takeda, Travere Therapeutics, and Ultragenyx.The research described was supported by NIH/National Center for Advancing Translational Science (NCATS) Einstein-Montefiore CTSA Grant Number UL1TR001073 and the National Niemann Pick Disease Foundation (NNPDF).
Publisher Copyright:
© 2021
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - Acid sphingomyelinase deficiency
KW - Biomarker
KW - Lyso-sphingomyelin
KW - Lysosomal storage diseases
KW - Nieman pick disease
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U2 - 10.1016/j.ymgmr.2021.100780
DO - 10.1016/j.ymgmr.2021.100780
M3 - Article
AN - SCOPUS:85109441713
SN - 2214-4269
VL - 28
JO - Molecular Genetics and Metabolism Reports
JF - Molecular Genetics and Metabolism Reports
M1 - 100780
ER -