Galabiosylceramide is present in human cerebrospinal fluid

Cerebrospinal fluid (CSF) contains glycosphingolipids, including lactosylceramide (LacCer, Gal beta(1,4)Glc beta-ceramide). LacCer and its structural isomer, galabiosylceramide (Gb(2), Gal alpha(1,4)Gal beta-ceramide), are classified as ceramide dihexosides (CDH). Gb(2) is degraded by alpha-galactosidase A (GLA) in lysosomes, and genetic GLA deficiency causes Fabry disease, an X-linked lysosomal storage disorder. In patients with Fabry disease, Gb(2) accumulates in organs throughout the body. While Gb(2) has been reported to be in the liver, kidney, and urine of healthy individuals, its presence in CSF has not been reported, either in patients with Fabry disease or healthy controls. Here, we isolated CDH fractions from CSF of patients with idiopathic normal pressure hydrocephalus. Purified CDH fractions showed positive reaction with Shiga toxin, which specifically binds to the Gal alpha(1,4)Gal beta structure. The isolated CDH fractions were analyzed by hydrophilic interaction chromatography (HILIC)-electrospray ionization tandem mass spectrometry (ESI-MS/MS). HILIC-ESI-MS/MS separated LacCer and Gb(2) and revealed the presence of Gb(2) and LacCer in the fractions. We also found Gb(2) in CSF from neurologically normal control subjects. This is the first report to show Gb(2) exists in human CSF. (C) 2020 The Authors. Published by Elsevier Inc.

Automated summary

It is the first report to show the existence of Gb(2) in human cerebrospinal fluid. Gb(2) is an important ceramide dihexoside that accumulates in patients with Fabry disease. By isolating and analyzing CDH fractions from CSF, the study revealed the presence of Gb(2) in healthy individuals.