Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder; a new report said that plasma lyso-sphingomyelin levels can be used to not only diagnose the rare disease but also predict severity and type.
A new report has found that plasma lyso-sphingomyelin (LSM) levels are a meaningful biomarker for acid sphingomyelinase deficiency (ASMD), not only to diagnose the disorder, but also to gauge its severity and type.
ASMD is an autosomal recessive lysosomal storage disorder resulting from ineffective sphingomyelin metabolism. The disease is rare, and has a wide clinical spectrum, according to the authors, whose findings appeared recently in Molecular Genetics and Metabolism.
LSM was previously identified as a useful biomarker to diagnose ASMD and to distinguish it from a similar, but biochemically distinct, disorder. Yet, the investigators said there have been no studies looking at the relationship between LSM level and ASMD severity.
“We hypothesized that LSM levels would be greater in patients with infantile neurovisceral disease when compared to chronic neurovisceral and visceral disease,” they wrote. “Additionally, we hypothesized that LSM levels would be positively associated with clinical severity in patients with chronic disease.”
To find out if their hypotheses were correct, the investigators evaluated data from 28 patients already enrolled in an ongoing natural history study of the disease. Among the 28 patients, 7 had the infantile neurovisceral phenotype (ASMD type A), 3 had chronic neurovisceral disease (ASMD type A/B), and the remaining had chronic visceral disease (ASMD type B).
The authors looked for connections between LSM levels and subtype, as well as links between LSM levels and clinical severity.
The analysis confirmed the authors’ hypotheses: All patients had elevated levels of LSM compared with a reference range. Patients with infantile ASMD had higher median levels of LSM vs patients with chronic ASMD: 386 ng/mL vs 133 ng/ML. Moreover, among patients with chronic ASMD, there was a positive correlation between LSM level and clinical severity.
One challenge and limitation of the study, the authors reported, was that there is no suitable validated clinical severity scoring system with which to assess disease severity in patients with chronic ASMD. There is one scoring system, but the authors said it was not used because it did not account for lung disease or neurological symptoms, which the authors said made it ill-suited to this study.
To get around that limitation, the authors consulted an expert in the field who evaluated each patient to assess their disease severity. The expert was blinded from LSM levels to prevent potential biases.
A second limitation was that infantile ASMD progresses rapidly. As a result, “All infants in this cohort were seen at a relatively advanced state of disease, which likely impacted their LSM levels,” the authors added.
They said their data could be used in a number of ways, including determining treatment eligibility, noting that enzyme replacement therapy (ERT) could be a potential treatment.
“While ERT is currently under development for individuals with chronic ASMD, recombinant enzyme is not indicated for patients with infantile ASMD, as it does not cross the blood-brain barrier,” they said.
The biomarker could also be useful to measure treatment response, in patients already on treatment, they added.
“In conclusion, this study offers preliminary data demonstrating a positive correlation between LSM levels and clinical severity in ASMD patients,” they wrote. “These results support further investigations into LSM as a biomarker for ASMD.”
Breilyn MS, Zhang W, Yu C, Wasserstein MP. Plasma lyso-sphingomyelin levels are positively associated with clinical severity in acid sphingomyelinase deficiency. Mol Genet Metab Rep. Published online July 7, 2021. doi:10.1016/j.ymgmr.2021.100780