Abstract 1976 Bi-allelic inactivating variants of lactosylceramide synthase B4GALT5 responsible for a novel congenital disorder of glycosylation involving glycosphingolipids

A 7-year-old girl of Italian ancestry presenting with developmental delay, intellectual disability, microcephalia, and bilateral cataract was found to carry compound heterozygous variants in the B4GALT5 gene (deposited in Decipher: ID 412221) encoding a galactosyltransferase acting on glucosylceramide as substrate and producing lactosylceramide (LacCer), the precursors of the bulk of glycosphingolipids, including gangliosides and globosides. We wanted to establish if B4GALT5 variants expressed in the patient are responsible for disease pathogenesis defining a novel and unexpected congenital disorder of glycosylation (CDG).