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Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses

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...

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Autores principales: Baydakova, Galina, Ilyushkina, Alex, Gaffke, Lidia, Pierzynowska, Karolina, Bychkov, Igor, Ługowska, Agnieszka, Wegrzyn, Grzegorz, Tylki-Szymanska, Anna, Zakharova, Ekaterina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151490/
https://www.ncbi.nlm.nih.gov/pubmed/32183018
http://dx.doi.org/10.3390/diagnostics10030155
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author Baydakova, Galina
Ilyushkina, Alex
Gaffke, Lidia
Pierzynowska, Karolina
Bychkov, Igor
Ługowska, Agnieszka
Wegrzyn, Grzegorz
Tylki-Szymanska, Anna
Zakharova, Ekaterina
author_facet Baydakova, Galina
Ilyushkina, Alex
Gaffke, Lidia
Pierzynowska, Karolina
Bychkov, Igor
Ługowska, Agnieszka
Wegrzyn, Grzegorz
Tylki-Szymanska, Anna
Zakharova, Ekaterina
author_sort Baydakova, Galina
collection PubMed
description 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.
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spelling pubmed-71514902020-04-20 Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses Baydakova, Galina Ilyushkina, Alex Gaffke, Lidia Pierzynowska, Karolina Bychkov, Igor Ługowska, Agnieszka Wegrzyn, Grzegorz Tylki-Szymanska, Anna Zakharova, Ekaterina Diagnostics (Basel) Article 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. MDPI 2020-03-13 /pmc/articles/PMC7151490/ /pubmed/32183018 http://dx.doi.org/10.3390/diagnostics10030155 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Baydakova, Galina
Ilyushkina, Alex
Gaffke, Lidia
Pierzynowska, Karolina
Bychkov, Igor
Ługowska, Agnieszka
Wegrzyn, Grzegorz
Tylki-Szymanska, Anna
Zakharova, Ekaterina
Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses
title Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses
title_full Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses
title_fullStr Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses
title_full_unstemmed Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses
title_short Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses
title_sort elevated lysogb3 concentration in the neuronopathic forms of mucopolysaccharidoses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151490/
https://www.ncbi.nlm.nih.gov/pubmed/32183018
http://dx.doi.org/10.3390/diagnostics10030155
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