Longevity & AgingGalactose Supplements Rescue Brain Lipid Defects in Rare Glycosylation Disorder
SLC35A2-CDG is a rare X-linked disorder where a defective UDP-galactose transporter impairs glycan attachment to proteins and lipids. This study found that protein glycosylation defects were surprisingly mild in patient fibroblasts, but lipid glycosylation—specifically glycosphingolipid (GSL) synthesis—was severely disrupted. Glucosylceramide accumulated while complex gangliosides were depleted. Oral galactose supplementation boosted UDP-galactose levels, improved its transport into the Golgi, and directly restored GSL synthesis in all patient cell lines tested. Hydroxylated GSLs, especially GM3, emerged as potential blood biomarkers. Because gangliosides are critical for brain function, their deficiency likely underlies the neurological symptoms of this disorder, opening new avenues for ganglioside-targeted therapies.
