Oligosaccharide Storage in Brains From Patients With Fucosidosis, Gm1‐gangliosidosis and Gm2‐gangliosidosis (Sandhoff's Disease)1

Analysis of whole autopsy brain from a patient with fucosidosis (α‐fucosidase deficiency) revealed minor storage of H‐antigen glycolipid [Fuc (α, 1→2) Gal‐GlcNAc‐Gal‐Glc‐Ceramide] and a slightly abnormal ganglioside composition in the form of a two‐fold elevation of GM1 and the presence of a fucose‐containing glycolipid (a minor component) which co‐migrated with GD1a. The major storage materials in fucosidosis brain were an oligosaccharide (Fuc‐Gal‐GlcNAc‐Man[Fuc‐Gal‐GlcNAc‐Man]‐ManGlcNAc) and a disaccharide [Fuc(α, 1→6)‐GlcNAc] in the approximate ratio of 5:1. Lesser amounts of a related oligosaccharide (Gal‐GlcNAc‐Man[Gal‐GlcNAc‐Man]‐Man‐GlcNAc) were isolated from the brain of patients with GM1‐gangliosidosis (Types I and II) where the major storage material is known to be GM1‐ganglioside (Gal (β, 1→3)GalNAc(β, 1→4) [NeuNAcf(α, 2→3) Gal(β, 1→4)Glc‐Ceramide). Similarly, a related oligosaccharide (GlcNAc‐Man [GlcNAc‐Man]‐Man‐GlcNAc) was isolated from the brain of a patient with a total deficiency of N‐acetyl‐β‐d‐hexosaminidase (Sandhoff variant of GM2‐gangliosidosis) where the major storage products are known to be GM2‐ganglioside (GalNAc (β 1→4) [NeuNAc (α, 2→3)Gal(β, 1→4)Glc‐Ceramine) and its asialo derivative. These studies indicate that glycoproteins containing at least 2 mol of l‐fucose per oligosaccharide unit are normally catabolized in human brain. Further, it appears that such glycoproteins are initially catabolized by an endo‐N‐acetylglucosaminidase to release an oligosaccharide which is then degraded by the sequential action of exo‐glycosidases.