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
AbstractMucopolysaccharidoses (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.
|Journal series||Diagnostics, ISSN 2075-4418, (N/A 70 pkt)|
|Keywords in English||globotriaosylsphingosine, mucopolysaccharidoses, heparan sulfate, glycosaminoglycans, biochemical marker, inherited metabolic diseases|
|License||Journal (articles only); published final; ; with publication|
|Score||= 70.0, 08-06-2020, ArticleFromJournal|
|Publication indicators||= 0.000; : 2018 = 2.489 (2)|
|Citation count*||1 (2020-07-21)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.