Glycogen Storage Disease

Glycogen storage diseases (GSDs) are inherited inborn errors of metabolism (IEM) involving carbohydrate metabolism. IEMs are often caused by single gene mutations that encode specific proteins: they are very relevant to pediatrics since these diseases may first manifest themselves in neonates or early childhood. IEMs should be considered in the differential diagnosis of any sick neonate. In general, IEMs result from the lack or insufficient level of specific enzymes that are needed to: (1) convert fat or carbohydrates to energy; (2) breakdown amino acids or other metabolites, allowing them to accumulate and become toxic. GSDs, depending on the specific type, can result from a failure to convert glycogen into energy and/or a toxic glycogen accumulation. All GSDs are due to a failure to use or store glycogen . Glycogen is a branched polymer with its monomeric units being glucose (Figure 1). After a meal, the level of glucose in plasma increases and stimulates the storage of excess glucose in cytoplasmic glycogen spherical. The liver contains the highest percent glycogen by weight (about 10%) whereas muscle can store about 2% by weight. Nevertheless, since the total muscle mass is greater than liver mass, the total mass of glycogen in muscle is about twice that of the liver. When needed, the glycogen polymer can be broken down into glucose monomers and utilized for energy production. Many of the enzymes and transporters for these processes are key to the etiology of GSDs. An increasing number of GSDs are being identified, but some are very rare. We will review the GSD type 0, 1, 2, 3, 4, 5, and 6 (see Figure 1). In the past, GSDs were also named by the discovering physician, as indicated in Table 1.