Reports of congenital disorders caused by mutations of molecules involved in the biosynthesis of sulfated glycosaminoglycans (GAGs) are accumulating [1–5]. Based on the marked progress in next-generation genome sequencing, causative genes of unknown genetic disorders have become easier to identify (Table 85.1). In addition to mutations in glycosyltransferases, sulfotransferases, and isomerases for GAG biosynthesis as well as enzymes modifying the GAG-core protein-linker region [1], mutations in transporters of UDP-sugars and active sulfate, which are donor substrates for each transferase, to the Golgi apparatus [5] as well as enzymes involved in their metabolism, also result in similar symptoms. Skeletal abnormalities are common in each genetic disorder, because chondroitin sulfate (CS) is a major component of cartilage and heparan sulfate (HS) is essential for bone differentiation. Patients with these congenital disorders show systemic abnormalities in various organs, including heart and kidney malformations, mental retardation, and immunodeficiency [3]. Although analysis of the mechanism regulating GAG biosynthesis is progressing, it has not been fully elucidated. Various treatments for each disease, especially gene therapy, are being considered, but implementation at the human level has yet to be realized.