Elevated LysoGb3 concentration in the neuronopathic forms of mucopolysaccharidoses

Galina Baydakova , Alex Ilyushkina , Lidia Gaffke , Karolina Pierzynowska , Igor Bychkov , Agnieszka Ługowska , Grzegorz Węgrzyn , Anna Tylki-Szymanska , Ekaterina Zakharova


Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders associated with impaired glycosaminoglycans (GAGs) catabolism. In MPS I, II, III, and VII, heparan sulfate (HS) cannot be degraded because of the lack of sufficient activity of the respective enzymes, and its accumulation in the brain causes neurological symptoms. Globotriaosylsphingosine (LysoGb3), the deacylated form of globotriaosylceramide (Gb3), is described as a highly sensitive biomarker for another lysosomal storage disease—Fabry disease. The connection between MPSs and LysoGb3 has not yet been established. This study included 36—MPS I, 15—MPS II, 25—MPS III, 26—MPS IV, and 14—MPS VI patients who were diagnosed by biochemical and molecular methods and a control group of 250 males and 250 females. The concentration of lysosphingolipids (LysoSLs) was measured in dried blood spots by high pressure liquid chromatography—tandem mass spectrometry. We have demonstrated that LysoGb3 concentration was significantly elevated (p < 0.0001) in untreated MPS I (3.07 + 1.55 ng/mL), MPS II (5.24 + 2.13 ng/mL), and MPS III (6.82 + 3.69 ng/mL) patients, compared to the control group (0.87 + 0.55 ng/mL). LysoGb3 level was normal in MPS VI and MPS IVA (1.26 + 0.39 and 0.99 + 0.38 ng/mL, respectively). Activity of α-galactosidase A (α-Gal A), an enzyme deficient in Fabry disease, was not, however, inhibited by heparan sulfate in vitro, indicating that an increase of LysoGb3 level in MPS I, MPS II, and MPS III is an indirect effect of stored MPSs rather than a direct result of impairment of degradation of this compound by HS. Our findings indicate some association of elevated LysoGb3 concentration with the neuronopathic forms of MPSs. The pathological mechanism of which is still to be studied.
Author Galina Baydakova
Galina Baydakova,,
, Alex Ilyushkina
Alex Ilyushkina,,
, Lidia Gaffke (FB/DMoB)
Lidia Gaffke,,
- Department of Molecular Biology
, Karolina Pierzynowska (FB/DMoB)
Karolina Pierzynowska,,
- Department of Molecular Biology
, Igor Bychkov
Igor Bychkov,,
, Agnieszka Ługowska
Agnieszka Ługowska,,
, Grzegorz Węgrzyn (FB/DMoB)
Grzegorz Węgrzyn,,
- Department of Molecular Biology
, Anna Tylki-Szymanska
Anna Tylki-Szymanska,,
, Ekaterina Zakharova
Ekaterina Zakharova,,
Journal seriesDiagnostics, ISSN 2075-4418, (N/A 70 pkt)
Issue year2020
Article number155
Keywords in Englishglobotriaosylsphingosine, mucopolysaccharidoses, heparan sulfate, glycosaminoglycans, biochemical marker, inherited metabolic diseases
URL https://doi.org/10.3390/diagnostics10030155
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)70
Score sourcejournalList
ScoreMinisterial score = 70.0, 08-06-2020, ArticleFromJournal
Publication indicators WoS Citations = 0.000; WoS Impact Factor: 2018 = 2.489 (2)
Citation count*1 (2020-07-21)
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