Glycosphingolipid synthesis is impaired in SLC35A2-CDG and improves with galactose supplementation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F25%3A10500010" target="_blank" >RIV/00216208:11110/25:10500010 - isvavai.cz</a>

Alternative codes found

RIV/00064165:_____/25:10500010

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=LZ-daBNBRe" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=LZ-daBNBRe</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00018-025-05759-w" target="_blank" >10.1007/s00018-025-05759-w</a>

Result language

angličtina

Original language name

Glycosphingolipid synthesis is impaired in SLC35A2-CDG and improves with galactose supplementation

Original language description

SLC35A2-CDG is an X-linked congenital disorder of glycosylation (CDG), characterized by defective UDP-galactose transport into the Golgi and endoplasmic reticulum and consequent insufficient galactosylation of glycans. Clinically, this translates into a range of predominantly neurological symptoms. Although the pathomechanism of this disorder is not fully understood, oral galactose supplementation has led to clinical and biochemical improvement in some patients. Here, we show that protein glycosylation (N- and O-linked) was only minimally disturbed in SLC35A2-CDG patient-derived fibroblasts. However, lipid glycosylation was significantly impaired, with accumulation of glucosylceramide and deficiency of digalactosylated glycosphingolipids (GSLs) and complex gangliosides. Galactose supplementation increased UDP-galactose, its transport into the Golgi, and improved deficient GSL synthesis through direct incorporation of the provided galactose. This improved GSL homeostasis in all patient-derived fibroblasts and in another SLC35A2 deficient cell model (CHO-Lec8). Additionally, SLC35A2-CDG serum analysis identified hydroxylated GSLs, particularly GM3, as potential disease biomarkers. Given the essential role of gangliosides in central nervous system function, their deficiency is likely a key factor in the neurological involvement of this disorder. These findings pave the way for new nutritional therapies with GSL supplements and highlight the importance of studying lipid glycosylation to better understand the complex pathophysiology of CDG.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30209 - Paediatrics

Project

<a href="/en/project/NU22-07-00474" target="_blank" >NU22-07-00474: Molecular genetic causes and biochemical consequences of Congenital disorders of glycosylation</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cellular and Molecular Life Sciences

ISSN

1420-682X

e-ISSN

1420-9071

Volume of the periodical

82

Issue of the periodical within the volume

1

Country of publishing house

CH - SWITZERLAND

Number of pages

17

Pages from-to

257

UT code for WoS article

001518870800001

EID of the result in the Scopus database

2-s2.0-105009357700