Chitotriosidase activity as additional biomarker in the diagnosis of lysosomal storage diseases

Olkhovych, N. V.

doi:10.15407/ubj88.01.069

Cited by 1 publication

(2 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Upon effective treatment, a rapid decrease in chitotriosidase plasma activity can be appreciated, as well as recurrence when treatment is interrupted, making it a useful marker to monitor therapy in Gaucher patients [109][110][111]. In ASMD, plasma levels of chitotriosidase are moderately increased [75,90,[111][112][113][114][115][116] and do not overlap with levels as observed in Gaucher patients [90,112,[114][115][116]. In the phase Ib trial of olipudase alfa, a decrease of chitotriosidase activity in plasma was observed [28].…”

Section: Macrophage Markersmentioning

confidence: 99%

“…A pitfall is that approximately 5% and 35% of the population is homozygous or heterozygous, respectively, for a 24 nucleotide duplication in the gene coding for chitotriosidase, resulting in absence of or decreased activity [117]. In this group of patients, CCL18 can serve as a biomarker [116]. The chemokine CCL18, also named pulmonary and activation-regulated chemokine (PARC), is excreted by lipid laden cells as well and seems to reflect alveolar macrophage activation [118].…”

Section: Macrophage Markersmentioning

confidence: 99%

See 1 more Smart Citation

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

Eskes

Sjouke

Vaz

et al. 2020

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

Pick type A/B disease, is a rare lipid storage disorder leading to accumulation of sphingomyelin and its precursors primarily in macrophages. The disease has a broad phenotypic spectrum ranging from a fatal infantile form with severe neurological involvement (the infantile neurovisceral type) to a primarily visceral form with different degrees of pulmonary, liver, spleen and skeletal involvement (the chronic visceral type). With the upcoming possibility of treatment with enzyme replacement therapy, the need for biomarkers that predict or reflect disease progression has increased. Biomarkers should be validated for their use as surrogate markers of clinically relevant endpoints. In this review, clinically important endpoints as well as biochemical and imaging markers of ASMD are discussed and potential new biomarkers are identified. We suggest as the most promising biomarkers that may function as surrogate endpoints in the future: diffusion capacity measured by spirometry, spleen volume, platelet count, low-density lipoprotein cholesterol, liver fibrosis measured with a fibroscan, lysosphingomyelin and walked distance in six minutes. Currently, no biomarkers have been validated. Several plasma markers of lipid-laden cells, fibrosis or inflammation are of high potential as biomarkers and deserve further study. Based upon current guidelines for biomarkers, recommendations for the validation process are provided.Acid Sphingomyelinase Deficiency (ASMD), also known as Niemann-Pick disease types A and B, is a rare lysosomal storage disorder (LSD) caused by mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, leading to strongly decreased activity of acid sphingomyelinase (ASM,. The enzyme ASM is mainly present in lysosomes and catalyzes hydrolysis of sphingomyelin (SM) to ceramide and phosphocholine [5,6] (see Fig. 1). In ASMD, SM and its precursor lipids accumulate in lysosomes, especially in macrophages. These lipid laden macrophages, Niemann-Pick cells, can be found in several tissues, mainly the spleen, liver and lungs [1],

show abstract