Inherited metabolic disorders of glycoconjugate metabolism

Abstract

Inherited metabolic disorders of glycoconjugate metabolism include congenital disorders of glycosylation (CDG)-disorders in biosynthesis of glycoconjugates; and some of the lysosomal storage diseases (LSD)-disorders of their degradation. This review summarizes the brief characteristics of metabolic pathways of synthesis and catabolism of glycoconjugates as well as the latest update of relevant enzymatic defects discovered in population. Every year the number of known subtypes of these disorders dramatically increases as a result of high-throughput analytical infrastructure applied. However, due to the broad spectrum of unspecifi c clinical symptoms, many patients remain undiagnosed or have wrong diagnosis with ineffective treatment. Thus, disorders of glycoconjugate metabolism should be considered and ruled out in any unexplained syndrome. The collaboration between scientists and physicians plays an important role in the progress of such personalized diagnostics, that is essential mainly for rare diseases (Tab. 2, Fig. 1, Ref. 49).

Sphingolipids and Cell Signaling: Relationship Between Health and Disease in the Central Nervous System

“…In 2020 Pakanova et al expand the concept of sphingolipidosis using the term glycoconjugate metabolism disorders, including glycan biosynthesis disorders, glycoconjugate catabolism, congenital glycosylation diseases, and lysosomal storage diseases [23]. Ryckman et al, 2020, reorganizes the division of glycosphingolipidoses into genetic disorders of biosynthesis, defects of degradation, and diseases of lysosomal deposit, very similar to the initial classification proposed by Platt et al, in 2014 [22, 93].…”

“…Regardless of the classification, sphingolipidoses are characterized by extensive clinical heterogeneity, mainly caused by the accumulation of partially degraded substrates, which can be observed from asymptomatic presentations to severe neonatal forms. It is common to find organomegaly, bone abnormalities, and CNS disorders that usually have a typically degenerative presentation [23,24]. The sphingolipids can start at very early stages of life, without meaning that they cannot observe later presentations, equally with varying degrees of severity [22].…”

“…The group of disorders caused by the disfunction of biosynthesis or catabolism of glycosphingolipids are known as sphingolipidoses [22], mainly caused by impaired lysosomal enzymes or by altered transport of cholesterol in the lysosomecytosol pathway. Due to the broad heterogeneity of this group, it was recently divided into genetic disorders of biosynthesis, defects of degradation, and diseases of lysosomal deposit [22,23]. All of them can course from asymptomatic presentations to severe neonatal forms, and show organomegaly, bone abnormalities, and CNS progressive impairment conducting to neuronal degeneration [24,25].…”