Biochemical and imaging parameters in acid sphingomyelinase deficiency: Potential utility as biomarkers

Mol Genet Metab 2020 May;130(1):16-26. doi: 10.1016/j.ymgme.2020.02.002.

PMID: 32088119

Eline C B Eskes, Barbara Sjouke, Frédéric M Vaz

Highlights: In this review, clinically important endpoints as well as biochemical and imaging markers of ASMD are discussed and potential new biomarkers are identified.

Abstract

Background: Acid Sphingomyelinase Deficiency (ASMD), also known as Niemann-Pick type A/B disease, is a rare lipid storage disorder that causes sphingomyelin and its precursors to accumulate largely in macrophages. The disease has a wide phenotypic range, from a deadly infantile form with severe neurological involvement (the infantile neurovisceral type) to a primarily visceral form with various degrees of lung, liver, spleen, and skeletal involvement (the chronic visceral type). The demand for biomarkers that predict or reflect disease development has increased as enzyme replacement therapy becomes more widely available. The use of biomarkers as surrogate markers for clinically meaningful objectives should be validated.

Objective: Clinically significant endpoints, as well as biochemical and imaging markers of ASMD, are described in this review, along with potential novel biomarkers.

Results and Conclusion: We propose the following biomarkers as the most potential surrogate endpoints in the future: spirometry-measured diffusion capacity, spleen volume, platelet count, low-density lipoprotein cholesterol, fibroscan-measured liver fibrosis, lysosphingomyelin, and six-minute walk distance. There are currently no validated biomarkers. Several plasma indicators of lipid-laden cells, fibrosis, and inflammation have strong biomarker potential and should be investigated further. Recommendations for the validation procedure are made based on existing biomarker guidelines.

Keywords: ASMD, Acid sphingomyelinase deficiency, Biochemical markers, Biomarkers, Imaging parameters, Niemann-Pick disease type B