Nutrition interventions in congenital disorders of glycosylation

CDG was discovered in 1979 and counts more than 160 disorders; until recent years, only MPI-CDG was treatable. Altering sugar fluxes and activating internal monosaccharide salvage pathways have recently shown efficacy in several other CDG affecting galactosylation and fucosylation. There is still a huge unmet need to develop treatments for GPI anchor disorders, presenting with severe developmental delay and epilepsy. New therapies, including chaperone and drug repurposing approaches (e.g., epalrestat), also affect glycosylation by altering sugar pools and stabilizing/activating defective enzymes. Unfortunately, gene therapy is still in early phases due to the lack of animal models in CDG. Congenital disorders of glycosylation (CDG) are a group of more than 160 inborn errors of metabolism affecting multiple pathways of protein and lipid glycosylation. Patients present with a wide range of symptoms and therapies are only available for very few subtypes. Specific nutritional treatment options for certain CDG types include oral supplementation of monosaccharide sugars, manganese, uridine, or pyridoxine. Additional management includes specific diets (i.e., complex carbohydrate or ketogenic diet), iron supplementation, and albumin infusions. We review the dietary management in CDG with a focus on two subgroups: N-linked glycosylation defects and GPI-anchor disorders. Congenital disorders of glycosylation (CDG) are a group of more than 160 inborn errors of metabolism affecting multiple pathways of protein and lipid glycosylation. Patients present with a wide range of symptoms and therapies are only available for very few subtypes. Specific nutritional treatment options for certain CDG types include oral supplementation of monosaccharide sugars, manganese, uridine, or pyridoxine. Additional management includes specific diets (i.e., complex carbohydrate or ketogenic diet), iron supplementation, and albumin infusions. We review the dietary management in CDG with a focus on two subgroups: N-linked glycosylation defects and GPI-anchor disorders. a large group of rare, inherited disorders that affect the complex metabolic process called glycosylation. proteins with covalently attached sugar derivates, or sugar chains. the process of creating, modifying, and attaching sugar chains to proteins and lipids. a complex lipid attaching a sugar chain to the membrane anchoring a protein. biochemically manufactured molecules (activated monosaccharides) locked in a miniscule lipid vacuole, preferentially administered in an infusion. single-sugar building block used by metabolism. a CDG type occurring due to pathogenic mutations in the gene MPI. CDG are named by the name of the affected gene followed by ‘-CDG’.